natriuretic-peptide--brain and Hypertension

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

Topics: Atrial Fibrillation; Atrial Natriuretic Factor; Heart; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides

Hypertension is a common pathological condition predisposing to a higher occurrence of cardiovascular diseases and events. Unfortunately, treatment of hypertension is still suboptimal worldwide. More efforts are needed to implement the availability of anti-hypertensive drugs. The family of natriuretic peptides, including atrial and brain natriuretic peptides (ANP and BNP), play a key role on blood pressure regulation through the natriuretic, diuretic and vasorelaxant effects. A large number of experimental and human studies, ranging from pathophysiological to genetic investigations, supported ANP as the most relevant component of the family able to modulate blood pressure and to contribute to hypertension development. On this background, it is expected that ANP-based therapeutic approaches may give a significant contribution to the development of efficacious therapies against hypertension. Since native ANP cannot be administered due to its short half-life, several approaches were attempted over the years to overcome the difficulties inherent to the ANP instability. These approaches included ANP recombinant and fusion peptides, gene therapy, inhibition of ANP degradation by neprilysin inhibition, and designer peptides. The most relevant achievements in the field are discussed in this article. Based on the available evidence, therapies targeting ANP represent efficacious and clinically applicable anti-hypertensive agents.

Topics: Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides

Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension and is associated with increased maternal and perinatal morbidity compared with preeclampsia alone. Distinguishing superimposed preeclampsia from chronic hypertension can be challenging because, in chronic hypertension, the traditional criteria for the diagnosis of preeclampsia, hypertension, and significant proteinuria can often predate the pregnancy. Furthermore, the prevalence of superimposed preeclampsia is unlikely to be uniformly distributed across this high-risk group but is related to the severity of preexisting endothelial dysfunction. This has led to interest in identifying biomarkers that could help in screening and diagnosis of superimposed preeclampsia and in the stratification of risk in women with chronic hypertension. Elevated levels of uric acid and suppression of other renal biomarkers, such as the renin-angiotensin aldosterone system, have been demonstrated in women with superimposed preeclampsia but perform only modestly in its prediction. In addition, central to the pathogenesis of preeclampsia is a tendency toward an antiangiogenic state thought to be triggered by an impaired placenta and, ultimately, contributing to the endothelial dysfunction pathognomonic of the disease. In the general obstetrical population, angiogenic factors, such as soluble fms-like tyrosine kinase-1 and placental growth factor, have shown promise in the prediction of preeclampsia. However, soluble fms-like tyrosine kinase-1 and placental growth factor are impaired in women with chronic hypertension irrespective of whether they develop superimposed preeclampsia. Therefore, the differences in levels are less discriminatory in the prediction of superimposed preeclampsia compared with the general obstetrical population. Alternative biomarkers to the angiogenic and renal factors include those of endothelial dysfunction. A characteristic of both preeclampsia and chronic hypertension is an exaggerated systemic inflammatory response causing or augmenting endothelial dysfunction. Thus, proinflammatory mediators, such as tumor necrosis factor-α, interleukin-6, cell adhesion molecules, and endothelin, have been investigated for their role in the screening and diagnosis of superimposed preeclampsia in women with chronic hypertension. To date, the existing limited evidence suggests that the differences between those who develop superimposed preeclampsia and those who do not a

Topics: Aldosterone; Angiogenic Proteins; Biomarkers; Chronic Disease; Cytokines; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Renin; Ultrasonography, Doppler; Uric Acid; Uterine Artery

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Cyclic GMP; Diabetes Mellitus; Fibrosis; Gene Expression Regulation, Developmental; Heart Atria; Heart Failure; Humans; Hypertension; Lipid Metabolism; Metabolic Syndrome; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Processing, Post-Translational; Pulmonary Arterial Hypertension; Receptors, Guanylate Cyclase-Coupled; Secretory Vesicles; Ventricular Remodeling; Water-Electrolyte Balance

Natriuretic peptides are peptide hormones which are involved in the regulation of blood pressure, water-mineral balance and multiple metabolic processes. The beginning of research on this group of hormones starts in 1981, when the deBold and collaborators discovered ANP. Eight natriuretic peptides have been described so far: ANP, BNP, CNP, DNP, urodilatin, uroguanylin, osteocrin, musculin and three receptors: NPR-A, NPR-B and NPR-C thanks to which these hormones accomplish their physiological functions. Determination of natriuretic peptide concentration in plasma is used in the diagnosis and treatment of heart failure and pulmonary embolism. Research results indicate that the determination of natriuretic peptides concentration in plasma may also be important in the acute coronary syndromes, subclinical complications of hypertension and atrial fibrillation. The concentration of natriuretic peptides is changing in many diseases. The beneficial effects of natriuretic peptides have led to the production of drugs that are their synthetic derivatives. These drugs are mainly used among patients with heart failure. Research is currently underway on the efficacy and safety of other synthetic natriuretic peptides.

Topics: Blood Pressure; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Vasodilator Agents

Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear.. Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups.. The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively.. Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.

Topics: Adult; Aged; American Heart Association; Antihypertensive Agents; Biomarkers; Cardiology; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Prospective Studies; Risk Assessment; Troponin T; United States

Obesity is a major risk factor for the development of chronic heart failure (CHF) and does not only pose diagnostic challenges, but also has prognostic implications for these patients. Paradoxically, obese patients with CHF have a better prognosis than thinner individuals. In recent years, it has been demonstrated that the adipose tissue, even in patients with HF, is not always detrimental, and that obesity may coexist with a phenotype of benign adiposity without systemic metabolic abnormalities. Experimental data have shown that natriuretic peptides (NPs), and in particular brain natriuretic peptide (BNP), play a major role in the communication of the heart with the adipose tissue. Body fat distribution and adipose tissue function show a large degree of heterogeneity among depots and may explain the complex relationship between NPs and body fat. NPs can affect both the quality and the behaviour of fatty tissue, promoting a healthy adipocyte phenotype, and can favourably affect body fat metabolism. In this article, we review the existing literature on the bidirectional effects of BNP and adipose tissue in HF and highlight the complexity of this relationship.

Topics: Adipose Tissue; Adiposity; Body Fat Distribution; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Phenotype; Prevalence; Prognosis; Risk Factors

Nocturnal polyuria (NP), the most common etiology of nocturia, can be caused by various medical conditions, including cardiovascular disease, obstructive sleep apnea, renal tubular dysfunction, as well as medications (eg, diuretics) and/or behavioral patterns. NP in the absence of underlying medical conditions has been described as NP syndrome and is thought be the result of impaired circadian release of endogenous arginine vasopressin. Desmopressin, a synthetic arginine vasopressin analog, has been shown to be an effective replacement therapy in adults with nocturia due to NP. Further studies on the subset of patients with NP syndrome are warranted to maximize benefit from antidiuretic treatment. In addition, a connection between the pathophysiological mechanisms underlying NP and essential hypertension has been suggested, and hypertension has been shown to be a significant risk factor for nocturia, while an association between NP and brain natriuretic peptide levels has also been reported in patients with nocturia. Hypertension is now viewed as a disorder of blood vessels and treatment is directed at the vasculature rather than the blood pressure, with the latter currently serving as a biomarker for arterial injury. Nocturia is thought to be associated with the beginning of this cardiovascular continuum as studies have reported a link between coronary heart disease and nocturia. Therefore, there is an increasing need to elucidate the complex mechanisms implicated in the association between nocturia and hypertension to promote the development of more individualized therapies for the treatment of nocturia.

Topics: Forecasting; Humans; Hypertension; Natriuretic Peptide, Brain; Nocturia; Polyuria; Prevalence; Vascular Diseases; Vascular Stiffness

Prevalence of cardiovascular (CV) disease is increasing worldwide. One of the most important risk factors for CV disease is hypertension that is very often related to obesity and metabolic syndrome. The search for key mechanisms, linking high blood pressure (BP), glucose and lipid dysmetabolism together with higher CV risk and mortality, is attracting increasing attention. Cardiac natriuretic peptides (NPs), including ANP and BNP, may play a crucial role in maintaining CV homeostasis and cardiac health, given their impact not only on BP regulation, but also on glucose and lipid metabolism. The summa of all metabolic activities of cardiac NPs, together with their CV and sodium balance effects, may be very important in decreasing the overall CV risk. Therefore, in the next future, cardiac NPs system, with its two receptors and a neutralizing enzyme, might represent one of the main targets to treat these multiple related conditions and to reduce hypertension and metabolic-related CV risk.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; Prognosis; Receptors, Atrial Natriuretic Factor; Risk Assessment; Risk Factors; Signal Transduction

LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Antihypertensive Agents; Atrial Natriuretic Factor; Biphenyl Compounds; Clinical Trials as Topic; Cough; Cyclic GMP; Diuresis; Drug Combinations; Heart Failure; Heart Ventricles; Humans; Hypertension; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Valsartan; Vasodilation

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Coronary Thrombosis; Early Diagnosis; Echocardiography, Three-Dimensional; Humans; Hypertension; Magnetic Resonance Imaging, Cine; Myocardial Ischemia; Natriuretic Peptide, Brain; Neoplasms; Primary Prevention; Radiotherapy; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy.

Topics: Addison Disease; Angiotensin-Converting Enzyme Inhibitors; Drug Dosage Calculations; Drug Monitoring; Female; Glucocorticoids; Heart Failure; Humans; Hypertension; Medication Therapy Management; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Renin; Symptom Assessment

Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction.

Topics: Aminobutyrates; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Clinical Trials as Topic; Drug Combinations; Heart Failure; Humans; Hypertension; Indans; Natriuretic Peptide, Brain; Neprilysin; Propionates; Pyridines; Receptors, Angiotensin; Renin-Angiotensin System; Risk Factors; Stroke Volume; Tetrazoles; Thiazepines; Valsartan

Cardiovascular disease is the leading cause of death amongst women worldwide. Cardiovascular risk assessment and primary prevention are important strategies to improve morbidity and mortality. In additional to the traditional risk factors, pregnancy complications such as pre-eclampsia and gestational diabetes increment future risk of developing cardiovascular complications. Additionally, several serum biomarkers are valuable measures for both risk assessment and predictors of clinical outcomes in women. The purpose of this review is to describe current risk stratification schemes as well as outline the role of obstetric history and serum biomarkers in adjusting risk stratification in women.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Hypertension; Lipids; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Pregnancy; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Sedentary Behavior; Smoking; United States; Women's Health

Peripartum cardiomyopathy is a form of heart failure occurring at the end of pregnancy or early in the postpartum period. Women may recover, have persistent cardiac dysfunction or suffer complications and death. Women who are African-American, older, hypertensive or have multiple gestation pregnancies have increased risk. Diagnosis and treatment may be delayed due to similarities between symptoms of normal pregnancy and heart failure. Echocardiography is essential for the diagnosis, and B-type natriuretic peptide can be helpful. Treatment for systolic heart failure must be adjusted during pregnancy, and anticoagulation may be indicated. Even after recovery, subsequent pregnancy confers substantial risk of worsening heart failure. Further investigations into the etiology, duration of treatment and risks for relapse are needed.

Topics: Age Factors; Black or African American; Breast Feeding; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Female; Humans; Hypertension; Multiple Birth Offspring; Natriuretic Peptide, Brain; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Risk Factors; United States

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cost-Benefit Analysis; Heart Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Stroke; Treatment Outcome

Hypertension is an established risk factor of cardiovascular morbidity and mortality. Although antihypertensive treatment reduces the risk of cardiovascular disease, it is impossible to identify all hypertensive subjects among the general population and to manage them in medical facilities considering the huge number of people with hypertension. Furthermore, more than half of cardiovascular events occur in individuals with mild hypertension or in those with a lower blood pressure. In this context, primary prevention of hypertension is an important public health problem. We investigated predictive values of several possible risk factors of hypertension in a general normotensive population. Normotensive subjects who visited our hospital for a physical checkup were enrolled and followed up for 4-5 years, with the endpoint being the development of hypertension. Each factor of metabolic syndrome was closely associated with the future onset of hypertension in subjects without hypertension, and the risk of hypertension markedly increased with overlapping metabolic disorders in individuals. Similarly, serum uric acid, the glomerular filtration rate, urinary albumin (even within the normal range), and brachial-ankle pulse wave velocity were independent risk factors of hypertension. These factors were also independent determinants of a future increase in the systolic blood pressure. An intensive targeted strategy focused on identified individuals at highest risk of developing hypertension is an attractive approach for the primary prevention of hypertension. [Review].

Topics: Albuminuria; Ankle Brachial Index; Atherosclerosis; Biomarkers; Blood Pressure; Cardiovascular Diseases; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Natriuretic Peptide, Brain; Predictive Value of Tests; Primary Prevention; Pulse Wave Analysis; Risk; Risk Factors; Uric Acid

Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696. Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 (sacubitril valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that has been developed for use in heart failure. This compound is composed of 2 molecular moieties in a single crystalline complex-the angiotensin receptor blocker valsartan and a neprilysin inhibitor prodrug-and has now been tested in hypertension, in a phase 2 trial in heart failure with preserved ejection fraction, and has demonstrated greater efficacy than enalapril in a phase 3 trial in heart failure with reduced ejection fraction. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Renin-Angiotensin System; Tetrazoles; Valsartan

Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions. The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress. Cardiac ventricular myocytes constitute the major source of BNP-related peptides. Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct. NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney). It has a longer half life than BNP and higher plasma concentration. BNP and NTproBNP tend to be higher in women and lower in obese individuals. They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection. NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP. A cut-off point 300 pg/ml has 99% sensitivity, 60%specificity and NPV 98%for exclusion of acute heart failure. NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD. Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction. Their release is due to myocardial stretch from right ventricular pressure overload.Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.

Topics: Amino Acid Sequence; Atrial Fibrillation; Biomarkers; Coronary Artery Disease; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Ventricular Dysfunction, Right

Assessment of ideal body weight in peritoneal dialysis (PD) patients is important for clinical practice. Fluid overload may produce hypertension, reduced arterial distensibility, left ventricular hypertrophy. All these are risk factors for mortality in PD patients: cardio- and cerebrovascular events are the main causes of morbidity and mortality in PD population. Nowadays, a clear and widely accepted definition of ideal body weight in PD patients does not exist. Probably the ideal body weight is the weight at which the extra cellular volume is normal. Many different tools have been used to assess the hydration status in dialysis patients. Ultrasonic evaluation of inferior vena cava diameter only assesses intravascular volume, and is also influenced by diastolic dysfunction and is thus a reflection of preload and not of tissue hydration. Direct measurement of extra cellular and total body water by dilution methods is considered as the golden standard, but these techniques are laborious and expensive. Parameters, such as brain natriuretic peptide (BNP) or NT-proBNP can reflect changes in hydration status and may help the nephrologist to estimate it. Natriuretic peptides are influenced both by preload and ventricular abnormalities and in patients with renal failure accumulation can occur. Bioimpedance is an accurate, reproducible, not expensive and not invasive technique that permits a good evaluation of hydration status in PD and can drive the nephrologist in his clinical choices. Clinical evaluation, strict control of body weight, diuresis, sodium and fluids intakes, bioimpedance monitoring and serum levels of natriuretic peptides may all together help us to maintain the PD patient euvolemic.

Topics: Body Water; Electric Impedance; Female; Humans; Hypertension; Ideal Body Weight; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Dialysis

Topics: Algorithms; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Diet; Evidence-Based Medicine; Exercise; Heart Failure; Humans; Hypertension; Natriuretic Agents; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Smoking Cessation; Treatment Outcome; Weight Loss

Interactions of glucose metabolism and chronic heart failure have been confirmed by many epidemiologic studies. The association of HbA1c with an increasing risk of heart failure clearly underlines the connection between both diseases. Coronary artery disease (CAD), hypertension and diabetic cardiomyopathy are long-term complications of diabetes mellitus, resulting in diabetic heart failure. Dysfunction of many regulation systems leads to specific diabetic cardiomyopathy, which has been firstly described by Rubler. A reduction in the cardiac expression of the Na-Ca exchanger pump and SERCA2a protein results in an imbalance in cardiac calcium handling. The overactive renin angiotensin aldosteron system (RAAS) also contributes to the impairment of myocardial function. Hyperlipidaemia, hpyerinsulinaemia and hyperglycaemia directly trigger diabetic cardiomyopathy. Generally chronic heart failure is a clinical diagnosis verified by blood tests like NT-proBNP and cardiac ultrasound. Recommendations on treatment of diabetic heart failure are based on subgroup analysis of the large heart failure trials.

Topics: Animals; Apoptosis; Autonomic Nervous System Diseases; Calcium; Cardiomyopathies; Coronary Disease; Cytokines; Diabetes Complications; Diabetic Neuropathies; Heart Failure; Homeostasis; Humans; Hyperglycemia; Hyperlipidemias; Hypertension; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress

Acute decompensated heart failure (ADHF) is a growing public health problem with high mortality and costs. ADHF often, if not usually, occurs in the setting of cardiovascular and noncardiovascular comorbidities as well as advanced age. New insights provide support for the concept of heart failure as a state of deficiency of and/or resistance to endogenous B-type natriuretic peptide. The primary goals of ADHF therapy are to relieve symptoms and optimize volume status with minimal side effects. Few therapies are proven to effectively do so. Nesiritide is a balanced vasodilator with favorable neurohumoral effects and is superior to placebo in providing rapid symptom relief and to nitroglycerin in reducing filling pressures. Recent trials confirm a lack of renal toxicity at recommended doses. An adequately powered multinational mortality trial is underway. Nesiritide represents a proven therapy for normotensive/hypertensive ADHF patients with severe symptoms at rest.

Topics: Acute Disease; Antihypertensive Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Costs; Heart Failure; Humans; Hypertension; Kidney; Natriuretic Peptide, Brain; Patient Selection; Risk Assessment; Treatment Outcome; Vasodilator Agents

Although the current value of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) to generally screen populations of "apparently well patients" remains promising but still undefined, the use of NT-proBNP to screen patients at high risk for heart disease (such as elderly patients, or patients with diabetes mellitus, hypertension, or known coronary artery disease) appears logical and is supported by data. NT-proBNP has strong prognostic value in such at-risk patients. However, the exact implications for clinical management after detection of an elevated NT-proBNP value should be driven by clinical judgment. At present, data suggest that when an elevated NT-proBNP is detected in an at-risk patient, it is a high-risk finding. In this context, consideration for a more in-depth cardiovascular workup, as well as initiation or intensification of medical therapies with proven benefits might be indicated.

Topics: Biomarkers; Diabetes Mellitus; Humans; Hypertension; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Risk Factors

Topics: Atrial Natriuretic Factor; Gene Expression Regulation; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Receptors, Atrial Natriuretic Factor; Transcription, Genetic

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study is the first, and, so far, the only endpoint trial in patients with hypertension and left ventricular hypertrophy (LVH) to show a divergent therapeutic outcome of one treatment modality over another with equivalent blood pressure control. The purpose of this article is to review post hoc sub-analyses of LIFE study data and other clinical studies that offer some insight into possible treatment-related differences contributing to the superior stroke outcome of losartan versus atenolol beyond blood pressure reduction.. Relevant randomized clinical trials and review articles were identified through a MEDLINE search of English-language articles published between 1990 and 2006 using the search terms losartan, atenolol, LIFE, hypertension, and LVH. Articles describing major clinical studies, new data, or mechanisms pertinent to the LIFE study were selected for review.. Differences in blood pressure or in the distribution of add-on medications were not evident between study groups in the LIFE study. Thus, the observed outcomes benefits favoring losartan may involve other possible mechanisms, including differential effects of losartan and atenolol on LVH regression, left atrial diameter, atrial fibrillation, brain natriuretic peptide, vascular structure, thrombus formation/platelet aggregation, serum uric acid, albuminuria, new-onset diabetes, and lipid metabolism. Alternative explanations for the LIFE study findings have also been put forward, including the choice of atenolol as an appropriate active comparator and differential effects between treatment groups on central pulse pressure. Additional clinical trials are needed to determine if the beneficial effects of losartan seen in LIFE are shared by other inhibitors of the renin-angiotensin system.. Sub-analyses of the LIFE study data suggest that losartan's stroke benefit may arise from a mosaic of mechanisms rather than a single action. Further studies are expected to continue to delineate the mechanisms of differential responses to treatments in LIFE.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atenolol; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Agents; Cohort Studies; Drug Utilization; Endothelium, Vascular; Follow-Up Studies; Heart Atria; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Models, Biological; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Protein Precursors; Randomized Controlled Trials as Topic; Research Design; Risk; Risk Factors; Stroke; Thrombosis; Treatment Outcome

Topics: Animals; Biological Assay; Biomedical Research; Cardiac Output, Low; Cross Reactions; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Protein Isoforms

Topics: Antihypertensive Agents; Biomarkers; Blood Pressure Monitoring, Ambulatory; Echocardiography; Electrocardiography; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Life Style; Natriuretic Peptide, Brain; Prognosis; Ventricular Function, Left

Natriuretic peptides (NP) are essential in mammals to regulate blood volume and pressure. The functional roles of NP are not limited to natriuresis and diuresis. Several peripheral and central actions of the peptides have been characterized. Studies on transgenic mice have revealed their key function in the regulation of cardiomyocyte growth. Plasma NP levels increase in patients with cardiovascular disorders and heart failure. They represent useful clinical markers for clinicians to diagnose heart diseases. The recent discovery of their potent lipolytic action in adipose tissue is a breakthrough in cardiovascular medicine. This new function of NP in the regulation of lipid metabolism offers interesting questions in the field of obesity, diabetes and cardiovascular diseases. This review will briefly describe the effects of NP on the cardiovascular system and lipid metabolism.

Topics: Adipose Tissue; Animals; Biomarkers; Cardiovascular System; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Kidney; Lipid Metabolism; Meta-Analysis as Topic; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Receptors, Atrial Natriuretic Factor; Signal Transduction

Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.

Topics: Cardiovascular Diseases; Celecoxib; Cell Proliferation; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Heart Failure; Hemostasis; Humans; Hypertension; Lactones; Naproxen; Natriuretic Peptide, Brain; Peptide Fragments; Pyrazoles; Sulfonamides; Sulfones

Hypertension involves the entire cardiovascular system, and hypertensive vascular disease may promote and exacerbate cardiac and renal dysfunction. We discuss the coexistence of cardiorenal disease as a manifestation of vascular involvement in hypertension, and the relationship of biomarkers of renal vascular involvement in hypertension with cardiovascular endpoints.. Markers of renal dysfunction, especially microalbuminuria, have been considered recently as potent predictors of cardiovascular morbidity and mortality in all explored populations, including hypertensive individuals. Microalbuminuria, per se, is related to vascular injury and to the increased glomerular permeability of albumin as a direct manifestation of renal vascular involvement in hypertension, a systemic vascular disease. Left ventricular hypertrophy in hypertension develops even before proteinuria or impairment of renal function. Factors including anemia, inflammation and hyperuricemia are either induced or exacerbated by renal vascular disease, and each of these may exert additional influence in determining the increased incidence of cardiovascular events with progressive renal dysfunction.. The development and progression of vascular disease is the primary determinant in the progressive cardiac and renal dysfunction observed in hypertension and, therefore, is the underlying mechanism of the overall clinical manifestations of cardiorenal disease. Commonly used biomarkers of renal and vascular function are important tools for determination of the progression and, hence, management of hypertensive disease and its complications.

Topics: Albuminuria; Biomarkers; C-Reactive Protein; Disease Progression; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Natriuretic Peptide, Brain; Renal Insufficiency; Uric Acid

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Defibrillators, Implantable; Diabetes Complications; Disease Progression; Female; Follow-Up Studies; Health Surveys; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Pacemaker, Artificial; Practice Guidelines as Topic; Prevalence; Severity of Illness Index; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Animals; Biomarkers; Heart Failure; Humans; Hypertension; Immunoenzyme Techniques; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet; Drug Therapy, Combination; Dyslipidemias; Endothelium, Vascular; Glomerular Filtration Rate; Health Behavior; Humans; Hypertension; Insulin Resistance; Kidney; Life Style; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Smoking; Smoking Cessation; Survival Analysis; Treatment Outcome; Vitamins

The number of patients requiring long-term haemodialysis is increasing throughout the world. Cardiovascular disease is much more common in these patients than in the general population and accounts for the majority of deaths. New approaches to management are clearly needed to reduce this excessive cardiovascular burden. We propose that circulating levels of the cardiac natriuretic peptides, B-type natriuretic peptide (BNP) in particular, might provide a useful, objective guide to the management of their hydration status and pharmacotherapy. An overview of the literature shows that plasma levels of the cardiac natriuretic peptides are increased in this patient population and reflect cardiac preload and afterload along with cardiac pathology, thereby providing an index of cardiovascular (especially cardiac) stress and distress. Circulating levels of the cardiac peptides change in parallel with cardiac load, especially across haemodialysis. Furthermore, there is robust evidence that natriuretic peptide levels are predictive of cardiovascular outcome in these patients. Accordingly, we hypothesize that management of their haemodialysis, and pharmacotherapy designed specifically to lower plasma BNP levels to, or close to, the normal range, will reduce the excessive burden on the cardiovascular system and thereby ultimately lower the incidence of cardiovascular disease. We outline, in broad terms, how a trial to test this hypothesis might be designed.

Topics: Biomarkers; Humans; Hypertension; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Renal Dialysis

Topics: Aged; Biomarkers; Cardiac Catheterization; Coronary Disease; Diabetes Complications; Echocardiography; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain

Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) are elevated in most patients with acute pulmonary embolism (APE) that results in right ventricular overload. Therefore, APE should be considered in the differential diagnosis of patients with acute dyspnea and abnormal levels of BNPs. Moreover, plasma BNPs have been proved to predict outcome in APE.. Low NT-proBNP or BNP levels characterize an uneventful hospital course, and NT-proBNP levels of <500 pg/mL identify patients who could potentially be candidates for care on a complete outpatient basis. Moreover, plasma NT-proBNP and BNP reflect the degree of right ventricular overload in APE. Plasma BNPs can also be elevated in chronic precapillary pulmonary hypertension and are strongly related to total pulmonary resistance. Elevated plasma levels of BNP/NT-proBNP and especially their further increase during follow-up are a potent predictor of poor survival.. Because levels of brain natriuretic peptides are elevated significantly not only in pathologic conditions that affect the left ventricle but also in clinical conditions that lead to isolated acute or chronic right ventricular overload, it could be proposed that these peptides should not be regarded as biomarkers of congestive heart failure, but as indicators of cardiovascular dyspnea.

Topics: Acute Disease; Diagnosis, Differential; Dyspnea; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Embolism; Ventricular Dysfunction, Right

Congestive heart failure remains a severe condition. Risk stratification is necessary to assess the prognosis and discuss the potential timing of heart transplant. Numerous criteria have been used, which may be combined to define prognostic scores which, however, are rarely used in routine. A few items, however, may be used to stratify the risk of mortality and sudden death.

Topics: Coronary Angiography; Echocardiography; Heart Failure; Humans; Hypertension; Liver Failure; Natriuretic Peptide, Brain; Oxygen Consumption; Renal Insufficiency; Risk Assessment; Stroke Volume

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnostic Techniques, Endocrine; Heart Failure; Humans; Hypertension; Hyperthyroidism; Immunoradiometric Assay; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Reference Values; Specimen Handling; Tachycardia, Supraventricular

Topics: Age Factors; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Catheterization; Cardiac Volume; Controlled Clinical Trials as Topic; Diagnosis, Differential; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler; Female; Heart Failure; Heart Rate; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Physicians, Family; Prognosis; Prospective Studies; Ventricular Dysfunction, Left

Topics: Adrenomedullin; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Coronary Disease; Diabetes Mellitus; Humans; Hypertension; Liver Failure; Mice; Natriuretic Peptide, Brain; Oxidative Stress; Peptides; Rats

Topics: Amino Acid Sequence; Animals; Calcium Signaling; Cardiac Output, Low; Cytokines; Endothelins; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Molecular Sequence Data; Natriuretic Peptide, Brain; Peptide Hydrolases; Renin-Angiotensin System; Sodium-Hydrogen Exchangers; Vasopressins

A HORMONE REVEALING VENTRICULAR DYSFUNCTION: B-type natriuretic peptide or Brain natriuretic peptide (BNP) is a neurohormone secreted by the ventricular myocytes in response to volume expansion and pressure overload. It is a sensitive marker of ventricular dysfunction in symptomatic and asymptomatic patients, and its dosage is correlated with the severity of the dysfunction. INDICATION FOR ITS DOSAGE IN HEART FAILURE: Since the results of recent studies, many authors recommend its routine use in heart failure, in order to confirm the diagnosis in difficult cases, assess severity, prognosis and the efficacy of treatment. Such use requires that the results of these studies be known and that the threshold value be adapted according to the age, concomitant diseases and indication of the dosage. OTHER AFFECTIONS: Its diagnostic and prognostic interest in acute coronary syndromes and hypertension is presently being studied.

Topics: Acute Disease; Angina, Unstable; Chronic Disease; Clinical Trials as Topic; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Factors; ROC Curve; Sensitivity and Specificity; Troponin; Ventricular Dysfunction; Ventricular Remodeling

The successful management of a cardiac allograft recipient centers around detection of allograft dysfunction early and preferably in a noninvasive manner. Up to this point, echocardiography or right heart catherization with endomyocardial biopsy are the only definitive methods available to diagnose allograft dysfunction. However, these methods do not reflect early structural changes and neurohormonal aberrations involved in allograft dysfunction. B-type natriuretic peptide (BNP) reflects ventricular wall stress and pressure and early studies have intimated potential usefulness of this marker in heart transplantation. Recent studies utilizing point-of-care BNP assay in heart transplant recipients have demonstrated elevated BNP levels at baseline compared with controls. Furthermore, the two most significant correlates of BNP levels are central hemodynamic perturbations despite preserved systolic function and presence of right sided cardiac dysfunction. Initial investigations have demonstrated BNP levels to serve as prognostic marker for cardiac related events and to track responses to therapeutic interventions. Further studies are needed to further assess the utility of BNP as surrogate marker for cardiac function and adaptation.

Topics: Biological Assay; Biomarkers; Graft Rejection; Heart Transplantation; Hemodynamics; Humans; Hypertension; Natriuretic Peptide, Brain; Prognosis; Transplantation Tolerance; Ventricular Dysfunction, Left

Natriuretic Peptides like BNP or NT Pro BNP are diagnostic and prognostic makers largely used in clinical practice. Ageing may increase these peptides, especially in case of comorbidities like renal failure or hypertension and require adjustment for age. Diagnostic value of natriuretic peptides seems however preserved in elderly people.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Electrocardiography; Female; Fluorescent Antibody Technique; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Radioimmunoassay; Reference Values; Sex Factors; Time Factors

Natriuretic peptide system plays a well-defined role in the regulation of blood pressure and fluid volume. Although the effects of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide) are mediated by specific biologic receptors, their plasma level is influenced by clearance receptors. It has been demonstrated that in hypertensive subjects plasma levels of natriuretic peptides are impaired; furthermore peptide receptor polymorphisms have been shown to be significantly associated with hypertension and cardiac hypertrophy. Studying normotensive subjects at high genetic risk of developing hypertension on the basis of family history makes it possible to investigate the role of natriuretic peptide system in the genesis of hypertension. It has been shown that plasma atrial and ventricular natriuretic peptide levels are significantly reduced in normotensive subjects with a family history of hypertension. Our study is the first one showing association among positive family history of essential hypertension and natriuretic peptide receptor polymorphisms. We identified a novel insertion/deletion polymorphism at position 15,129 in the 3'-untranslated region (3'-UTR) of NPRA receptor mRNA. The NPRA gene deletion variant is associated with hypertensive family history and higher systolic blood pressure. The "deletion 15129" variant might participate in the functional impairment of natriuretic peptide system defining an increased genetic susceptibility to hypertension.

Topics: Gene Deletion; Guanylate Cyclase; Humans; Hypertension; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Polymorphism, Genetic; Receptors, Atrial Natriuretic Factor

Vasopeptidase inhibitors are a group of agents capable of inhibiting neutral endopeptidase and angiotensin-converting enzymes, which leads to potentiation of natriuretic peptide actions and suppression of the renin-angiotensin-aldosterone system. With this distinctively characteristic mechanism, these agents have emerged as a new drug class for management of hypertension and heart failure. Several vasopeptidase inhibitors are under clinical investigation. Omapatrilat is the most studied agent in this class. Clinical studies of omapatrilat in hypertension have consistently shown the agent's effectiveness in a variety of patient populations. In patients with heart failure, omapatrilat significantly improved neurohormonal and hemodynamic status. Long-term effects of omapatrilat in patients with heart failure recently were compared with those of conventional therapy in a large phase II trial. Results of the study appear promising. Large clinical trials are ongoing, and additional information regarding safety and efficacy from these studies may help define the place in therapy for this agent.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypertension; Lisinopril; Mesylates; Natriuretic Peptide, Brain; Neprilysin; Pyridines; Randomized Controlled Trials as Topic; Thiazepines; Tyrosine

Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiomyopathies; Down-Regulation; Guanylate Cyclase; Heart Failure; Humans; Hypertension; Isoenzymes; Natriuretic Peptide, Brain; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; Structure-Activity Relationship

Monitoring of 24-hour ambulatory blood pressure(ABPM), measurements of circulating vasoactive substances and microalbuminuria, and assessment of gene polymorphisms as genetic markers are introduced to detect and evaluate hypertension. Classifications of ABPM based on impact on risks of cardiovascular diseases have been currently available. Plasma level of brain natriuretic peptide(BNP), a cardiac hormone, increases markedly in congestive heart failure, in proportion to its severity, and is evaluated as a potential index of severity of heart failure. In addition, serum level of hepatocyte growth factor(HGF), a member of endothelium specific growth factors, in hypertension might be useful for evaluating the presence of complications and degree of endothelial dysfunction. In diabetes mellitus, onset of microalbuminuria appeared as an important sign of early nephropathy. There is growing evidence that microalbuminuria is an independent predictor of atherosclerosis and premature death in the general population. Current studies have shown that gene polymorphisms including components of the renin-angiotensin-aldosterone system may be possible genetic markers for hypertension and its associated cardiovascular diseases. Our data suggest positive linkages between hypertension and 4 gene polymorphisms including angiotensinogen Met235Thr, angiotensin converting enzyme I/D, aldosterone synthase CYP11B2 T-344C, and endothelial nitric oxide synthase Glu298Asp in the Aomori population.

Topics: Albuminuria; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Hepatocyte Growth Factor; Humans; Hypertension; Natriuretic Peptide, Brain; Polymorphism, Genetic; Renin-Angiotensin System; Risk Factors; Severity of Illness Index

The literature review reflects new aspects of humoral regulation in hypertension and target-organ damages with special regard to natriuretic peptide system(NPS) and adrenomedullin(AM). NPS and AM are recently discovered regulators which serve as antihypertensive and target-organ protective factors. These peptides have both diuretic and natriuretic properties and a relaxing effect on the vasculature. Moreover, they antagonize the proliferative and hypertrophic stimuli in the vasculature and heart. Recently, progressive technics of molecular biology clearly revealed crucial roles of these peptides for cardiovascular regulation in both normal and pathological states including hypertension and related organ damages. Natriuretic peptides, potentially AM, are new therapeutic tools for heart failure and main targets for further development of new antihypertensive drugs such as vasopeptidase inhibitor.

Topics: Adrenomedullin; Animals; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Natriuretic Peptide, Brain; Peptides

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Cattle; Dogs; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; RNA, Messenger; Swine; Vasodilation

Vasopeptidase inhibition is a new concept in cardiovascular therapy. It involves simultaneous inhibition with a single molecule of two key enzymes involved in the regulation of cardiovascular function, neutral endopeptidase (EC 24.11; NEP) and angiotensin-converting enzyme (ACE). Simultaneous inhibition of NEP and ACE increases natriuretic and vasodilatory peptides (including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP] of myocardial cell origin, and C-type natriuretic peptide [CNP] of endothelial cell origin) and increases the half-life of other vasodilator peptides including bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide system, vasopeptidase inhibitors (VPIs) reduce vasoconstriction and enhance vasodilation, thereby decreasing vascular tone and lowering blood pressure. Omapatrilat, a heterocyclic dipeptide mimetic, is a novel vasopeptidase inhibitor and a single molecule that simultaneously inhibits NEP and ACE with similar inhibition constants. Unlike ACE inhibitors, omapatrilat demonstrates antihypertensive efficacy in low-, normal-, and high-renin animal models. Unlike NEP inhibitors, omapatrilat provides a potent and sustained antihypertensive effect in spontaneously hypertensive rats (SHR), a model of human essential hypertension. In animal models of heart failure, omapatrilat is more effective than ACE inhibition in improving cardiac performance and ventricular remodeling and prolonging survival. Omapatrilat effectively reduces blood pressure, provides target-organ protection, and reduces morbidity and mortality from cardiovascular events in animal models. Omapatrilat is the first VPI to enter advanced USA clinical trials. Omapatrilat appears to be a safe, well-tolerated and effective antihypertensive in humans. Vasopeptidase inhibition is a novel and efficacious strategy for treating cardiovascular disorders, including hypertension and heart failure, that may offer advantages over currently available therapies.

Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neprilysin; Peptidyl-Dipeptidase A; Pyridines; Thiazepines

There are significant gender-specific differences in the incidence of hypertension and the clinical outcome of cardiovascular disease between premenopausal women and age-matched men, suggesting that sex hormones such as estrogen (E) might be responsible for the observed cardioprotective effects. This cardioprotective action of E is thought to involve lipoproteins. However, the effect of E on the lipid profile accounts for about 50% of the reduction in cardiovascular disease, indicating that there might be other mechanisms by which E exerts its cardioprotective effects. At present, the underlying mechanism of E action is poorly understood. In this review, the interplay between E, the natriuretic peptides (NP) and the renin-angiotensin system (RAS) is examined. It is hypothesized that E might, through endocrine and/or paracrine action, modulate cardiac NP in females by affecting the RAS either directly or indirectly.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Estrogens; Female; Homeostasis; Humans; Hypertension; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Rats; Receptors, Estrogen; Renin-Angiotensin System; Testosterone

Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.

Topics: Animals; Atrial Natriuretic Factor; Cell Differentiation; Guanylate Cyclase; Humans; Hypertension; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Nitric Oxide; Proteins; Receptors, Atrial Natriuretic Factor; Signal Transduction

Natriuretic peptides are produced in the brain, heart and vasculature, and cause vasodilation, sodium excretion, and diuresis. Recent advances indicate that they play important roles in blood-pressure homeostasis, both in normal and in pathophysiological conditions. Although therapeutic interventions which elevate plasma natriuretic peptide levels do not have great antihypertensive efficacy, animal studies suggest that they may be useful in combination treatment strategies.

Topics: Animals; Atrial Natriuretic Factor; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Receptors, Peptide

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Central Nervous System; Dogs; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Rats; Renin; Renin-Angiotensin System; Sheep

The natriuretic peptide family consists of three members: atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Atrial and brain natriuretic peptides possess similar effects, causing natriuresis, vasodilation, and suppression of the renin-angiotensin-aldosterone system. C-type natriuretic peptide has been suggested to exert its predominant effect on the vasculature, eliciting vasodilation and inhibiting the proliferation of vascular smooth muscle cells. Numerous studies have broadened our current knowledge of the regulation of natriuretic peptide gene expression, biosynthesis, and secretion, as well as structure of specific receptors. This has led to a better understanding of the renal, cardiovascular, and endocrine actions of natriuretic peptides in both normal and pathophysiological states, including hypertensive disease. Development of nonpeptide neutral endopeptidase inhibitors and antagonists for natriuretic peptide receptors may reveal the range of potential therapeutic application of atrial and other natriuretic peptides in hypertension.

Topics: Animals; Atrial Natriuretic Factor; Hemodynamics; Humans; Hypertension; Kidney; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins

Topics: Atrial Natriuretic Factor; Humans; Hypertension; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins

Topics: Animals; Atrial Natriuretic Factor; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Heart Diseases; Heart Failure; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Protease Inhibitors

Topics: Animals; Humans; Hypertension; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Receptors, Atrial Natriuretic Factor

Topics: Animals; Atrial Natriuretic Factor; Drug Therapy, Combination; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neprilysin; Nerve Tissue Proteins; Peptide Fragments

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Signal Transduction

To evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) in hypertension, hemodynamic effects of human ANP and antiserum against rat ANP were investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of human ANP caused greater hypotension associated with a decrease of cardiac output in SHR than in WKY, which suggests that SHR have enhanced responsiveness to exogenous ANP. The antiserum increased blood pressure and cardiac output, with the latter being significantly greater in SHR than in WKY. These results suggest that endogenous ANP counteract, in part, the maintenance of hypertension. In addition, hemodynamic and renal excretory effects of brain natriuretic peptide (BNP), a novel natriuretic peptide identified from porcine, were studied in SHR and WKY. BNP caused marked natriuresis and hypotension in a dose-dependent fashion, as observed with ANP. Not only ANP but also BNP may have a role in the regulation of blood pressure and water-electrolyte balance.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Humans; Hypertension; Molecular Sequence Data; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Swine

Topics: Adult; Biomarkers; C-Reactive Protein; Diet; Dietary Approaches To Stop Hypertension; Humans; Hypertension; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Sodium; Troponin I; Troponin T

Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management.. To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF.. The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included.. Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily.. Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events.. Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04).. In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF.. ClinicalTrials.gov Identifier: NCT04687111.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Female; Heart Atria; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Neprilysin; Stroke Volume; Tetrazoles; Valsartan

Sacubitril valsartan and valsartan are the first new drugs approved for angiotensin receptor neprilysin lysine inhibitors (ARNIs) in outpatients with chronic heart failure (CHF) and hypertension. Compared with enalapril, sacubitril valsartan and valsartan have been shown to reduce the mortality and morbidity of cardiovascular diseases. However, there is little actual evidence regarding the efficacy of ARNIs in hypertensive patients with CHF.. From January 2019 to January 2021, 60 patients with hypertension and chronic heart failure were diagnosed and treated in our hospital. The patients were randomly divided into an observation group and a control group, with 30 cases in each group. The control group was given valsartan, the observation group was given sacubitril valsartan, and both groups were treated for six months. The endothelium-dependent vasodilation (EDD) function of the brachial artery and serum nitric oxide (NO), endothelin-1 (ET-1), carotid artery intima-media thickness, and glomerular filtration, excess rate (eGFR), and left ventricular ejection fraction (LVEF) were compared between the two groups of patients before and after treatment. The serum adiponectin (APN), matrix metalloproteinase-9 (MMP-9), and brain natriuretic peptide (BNP) levels were compared before and after treatment.. The total effective rate of treatment in the research group was higher than that in the control group (. In the treatment of hypertension and chronic heart failure, sacubitril valsartan can improve the clinical symptoms of patients to the greatest extent and can significantly improve the levels of LVEF, LVEDD, NT-proBNP, heart function, and other indicators. Sacubitril valsartan can increase serum APN levels, reduce MMP-9 and BNP levels, and have good clinical effects. Sacubitril valsartan has a protective effect on the vascular endothelial function of patients with hypertension and CHF. However, these results need to be confirmed in studies involving more subjects and require longer follow-up times.

Topics: Adiponectin; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Carotid Intima-Media Thickness; Drug Combinations; Endothelium; Heart Failure; Humans; Hypertension; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Stroke Volume; Treatment Outcome; Valsartan; Ventricular Function, Left

Hypertension is a vital risk factor for heart failure, while cardiac rehabilita-tion can effectively improve cardiac function of heart failure patients. This study aimed to determine the impact of cardiac rehabilitation on microRNA-423-5p in hypertensive patients with heart failure with a moderately reduced ejection fraction.. Sixty hypertensive patients with heart failure with a moderately reduced ejec-tion fraction were randomly divided into cardiac rehabilitation group and positive control group with 30 cases per group, while 30 hypertensive patients without heart failure were recruited as negative control group. The cardiac rehabilitation group and positive control group were treated with 1-month cardiac rehabilitation combined with the routine treat-ment and routine treatment only, respectively. The New York Heart Association classi-fication, 6-minute walking test, and color Doppler echocardiography were adopted to detect cardiac function. Meanwhile, the expression of microRNA-423-5p and N-terminal pro-B-type natriuretic peptide was determined via Real-Time Fluorescence Quantitative PCR and electrochemiluminescence immunoassay. The diagnostic potential of microR- 423-5p and N-terminal pro-B-type natriuretic peptide was assessed by ROC curve analy- sis and multivariate linear regression model.. Patients in cardiac rehabilitation group displayed significantly lower expression of microR-423-5p and better results of New York Heart Association classification, 6-min-ute walking test, and color Doppler echocardiography than those in positive controlgroup (P < .05). ROC analysis showed that microR-423-5p (AUC = 0.785; 95% CI: 0.686- 0.865; sensitivity = 73.33%; specificity = 73.33%) had better specificity and accuracy thanN-terminal pro-B-type natriuretic peptide (AUC=0.721; 95% CI: 0.617-0.811; sensitiv- ity = 81.67%; specificity = 63.33%).. MicroR-423-5p was implicated in left ventricular hypertrophy and might be a potential biomarker for assessing the therapeutic effect of cardiac rehabilitation on hypertensive patients with heart failure with a moderately reduced ejection fraction.

Topics: Biomarkers; Cardiac Rehabilitation; Circulating MicroRNA; Heart Failure; Humans; Hypertension; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.. The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.. A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined.. Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63).. Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.

Topics: Antihypertensive Agents; Biomarkers; Blood Pressure; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Risk Factors; Troponin T

Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.. To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.. This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.. Participants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0).. The primary outcome of this ancillary study was HF and mortality.. Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected.. Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.. ClinicalTrials.gov Identifier: NCT01206062.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Troponin T

Catheter ablation is an established therapy for atrial fibrillation but is limited by recurrence; efforts have been made to identify biomarkers that predict recurrence. We investigated the effect of baseline NT-proBNP on AF recurrence following catheter ablation in patients randomized to aggressive (< 120/80 mmHg) or standard blood pressure management (< 140/90 mmHg) in the Substrate Modification with Aggressive Blood Pressure Control trial (SMAC-AF).. The SMAC-AF study included 173 patients resistant or intolerant to at least one class I or III antiarrhythmic drug. We studied the effect of baseline NT-proBNP on the primary outcome of AF recurrence > 3 months post-ablation.. Of the 173 patients, 88 were randomized to the aggressive cohort, and 85 into the standard group. The primary outcome occurred in 61.4% of those in the aggressive arm, versus 61.2% in the standard arm. In the aggressive group, logNT-proBNP predicted recurrence (HR 1.28, p = 0.04, adjusted HR 1.43, p = 0.03), while in the standard cohort, it did not (HR 0.94, p = 0.62, adjusted HR 0.83, p = 0.22). NT-proBNP ≥ 280 pg/mL also predicted occurrence in the aggressive (HR 1.98, p = 0.02) but not the standard cohort (HR 1.00, p = 1.00).. We conclude that pre-ablation NT-proBNP may be useful in predicting recurrence in hypertensive patients and identifying patients who benefit from aggressive blood control and upstream therapies.. NCT00438113, registered February 21, 2007.

Topics: Action Potentials; Aged; Antihypertensive Agents; Atrial Fibrillation; Biomarkers; Blood Pressure; Canada; Catheter Ablation; Cryosurgery; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke.. RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF.. In the multivariable model, older age (odds ratio for 10-year increase, 1.99 [95% CI, 1.78-2.23];. Besides age, the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after embolic stroke of undetermined source. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Topics: Administration, Oral; Age Factors; Aged; Aspirin; Atrial Fibrillation; Body Mass Index; Dabigatran; Double-Blind Method; Embolic Stroke; Female; Humans; Hypertension; Male; Middle Aged; Models, Cardiovascular; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Recurrence; Risk Factors

Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.. We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.. A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2±4.2 ml per minute per 1.73 m. Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).

Topics: Aged; Albuminuria; Blood Pressure; Chlorthalidone; Creatinine; Diuretics; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Severity of Illness Index; Sodium Chloride Symporter Inhibitors

The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.. The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.. DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.. Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: -27% to -7%) and hs-CRP by 13% (95% CI: -24% to -1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: -24% to -14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: -31% to -7%) and NT-proBNP by 23% (95% CI: -32% to -12%), whereas hs-CRP was not significantly changed (-7%; 95% CI: -22% to 9%) compared with the high sodium-control diet.. Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH - Sodium]; NCT00000608).

Topics: Adult; Biomarkers; C-Reactive Protein; Diet, Sodium-Restricted; Dietary Approaches To Stop Hypertension; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

Metformin is the most widely used oral antihyperglycemic agent for patients with type 2 diabetes mellitus (T2DM). Despite the possible benefits of metformin on diabetes mellitus (DM) and heart failure (HF), acute or unstable HF remains a precaution for its use.. The aim of the present prospective randomized controlled trial was to assess whether metformin treatment has beneficial effects on patients with T2DM with hypertension without overt HF.. A total of 164 patients (92 males, 72 females; median age 66 years) were included in this study. Patients with T2DM with a history of hypertension were randomized 1:1 to treatment for 1 year with either metformin (metformin-treated group) or other hypoglycemic agents (control group). The primary endpoints were changes in brain natriuretic peptide (BNP) levels, left ventricular (LV) mass index, and indicators of LV diastolic function. We also evaluated changes in both clinical findings and blood laboratory examination data.. We observed no significant changes between baseline and 1-year post-treatment in LV mass index, BNP levels, or E/e' (early diastolic transmitral flow velocity/early diastolic mitral annular velocity; an indicator of LV diastolic function) in either the metformin-treated (n = 83) or the control (n = 81) groups. The metformin-treated group had a significant reduction of body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C), but the control group did not. We determined that renal function, including serum creatinine and estimated glomerular filtration rate, deteriorated significantly in the control group but not in the metformin-treated group.. LV mass and diastolic function were not affected after 1 year of metformin treatment in patients with T2DM. However, we observed benefits in terms of reductions in both BMI and LDL-C levels and preservation of renal function.. UMIN000006504. Registered 7 October 2011.

Topics: Aged; Body Mass Index; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Heart Ventricles; Humans; Hypertension; Hypoglycemic Agents; Male; Metformin; Natriuretic Peptide, Brain; Organ Size; Treatment Outcome; Ventricular Function, Left

Statins have multiple anti lipid effects, such as anti-inflammatory, anti-oxidation and anti arteriosclerosis, which are beneficial to improve cardiac function. Statins can effectively improve left ventricular remodeling and protect ventricular diastolic function. In this study, the effects of statin therapy on diastolic function and BNP level and exercise tolerance after exercise were observed by statins in patients with diastolic dysfunction. The results showed that after atorvastatin treatment, the exercise BNP decreased in the treatment group, which was significantly different from that before treatment and in the control group (P<0.05). This study demonstrated that atorvastatin was used to treat patients with diastolic dysfunction and exercise hypertension by lowering blood pressure and reducing exercise SBP, anti-inflammatory and improving vascular endothelial function.

Topics: Aged; Atorvastatin; Blood Pressure; Double-Blind Method; Echocardiography; Exercise; Exercise Tolerance; Female; Heart Failure, Diastolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function, Left

Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Blood Pressure; Cross-Over Studies; Diuresis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Peptide Fragments; Sodium Chloride, Dietary; Tetrazoles; Time Factors; Valsartan

Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial.. Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared.. Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar.. Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.

Topics: Acute Disease; Aged; Antihypertensive Agents; Blood Pressure; Cause of Death; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Hypertension; Injections, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Nitroglycerin; Peptide Fragments; Piperazines; Ventricular Function, Left

A trial of telmisartan prevention of cardiovascular disease (ATTEMPT-CVD) was performed to compare the effects of angiotensin II receptor blocker (ARB) therapy and those of non-ARB standard therapy on biomarker level changes and the incidence of cardiovascular events in hypertensive patients.. In this multicenter, open-label, randomized, parallel-group, comparative study, the effects of ARB therapy and those of non-ARB standard therapy on urinary albumin creatinine ratio (UACR) and plasma brain natriuretic peptide (BNP) level changes were investigated for three years from the start of antihypertensive treatment as the primary endpoints. The incidences of cardiovascular composite events were compared between the two groups, and the relationship between the incidence of the events and biomarker changes were investigated as secondary endpoints. The study started with 615 patients in the ARB group and 613 patients in the non-ARB group. The ARB group had a significant effect on UACR and plasma BNP level changes compared with the non-ARB group. Fewer cardiovascular events occurred in the ARB group, but the difference was not statistically significant. UACR and plasma BNP levels at baseline were associated with cardiovascular events.. This study provided the first evidence that ARB treatment caused a smaller increase in plasma BNP and a greater decrease in UACR than non-ARB treatment, independently of blood pressure control, and gives a novel insight into the significance of BNP and UACR as predictors of cardiovascular and renal risk on antihypertensive treatment.

Topics: Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Benzoates; Biomarkers; Blood Pressure; Cardiovascular Diseases; Creatinine; Female; Humans; Hypertension; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Telmisartan; Time Factors; Treatment Outcome

It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk-lowering effect against AF recurrence in paroxysmal AF hypertensive patients.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Atrial Fibrillation; Benzimidazoles; Benzoates; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Drug Combinations; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Prospective Studies; Telmisartan; Treatment Outcome

We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination.. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index.. High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.

Topics: Aged; Antihypertensive Agents; Area Under Curve; C-Reactive Protein; Case-Control Studies; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Hypertension; Immunoglobulin G; Immunoglobulin M; Lipoproteins, LDL; Logistic Models; Male; Malondialdehyde; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Risk Factors; ROC Curve

The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up.. The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat.. At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p=0·0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p. During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.. Swedish Heart-Lung Foundation, Swedish Foundation for Strategic Research, and Uppsala Clinical Research Center.

Topics: Acute Coronary Syndrome; Adult; Aged; Biomarkers; Diabetes Complications; Female; Follow-Up Studies; Heart Conduction System; Humans; Hypertension; Male; Middle Aged; Minimally Invasive Surgical Procedures; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prospective Studies; Scandinavian and Nordic Countries; Secondary Prevention; Time Factors; Treatment Outcome; Troponin T

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post-dialysis ratio of NO to ET-1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post-dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre-dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre-dialysis and post-dialysis determinations. Compared with blood angiotensin-II, ALD, ACE, NOR, adrenomedullin, N-terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET-1 plasma concentrations may play a predominant role in the pathogenesis of IDH.

Topics: Adrenomedullin; Adult; Aged; Aldosterone; Angiotensin II; Endothelin-1; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Norepinephrine; Peptidyl-Dipeptidase A; Renal Dialysis

This EnligHTN I nonrandomized substudy investigated the effect of multielectrode renal denervation (RDN) on cardiac and neurohumoral adaptations.. Eighteen patients with true drug-resistant hypertension [age: 56 ± 10 years, 12 men, BMI: 33.6 ± 5.4 kg/m, office blood pressure (BP) by automatic device (Omron): 182 ± 19/97 ± 18 mmHg and ambulatory BP (Spacelabs): 153 ± 16/87 ± 15 mmHg receiving 4.5 antihypertensive drugs/day] and left ventricular hypertrophy underwent multielectrode RDN (EnligHTN system; St. Jude Medical), whereas 10 patients served as controls. Both groups were followed-up for 6 months.. Demographic data were homogenous between both patient groups. In addition to reduction of office (-42/-17 mmHg, P < 0.001) and ambulatory (-19/-9 mmHg, P < 0.001) BP, RDN contributed to attenuation of left ventricular mass index from 140.0 ± 17.0 g/m (57.9 ± 7.9 g/m) to 126.7 ± 19.2 g/m (52.6 ± 8.4 g/m) (P < 0.01 for both) and left atrial diameter from 42.4 ± 4.3 to 40.6 ± 3.6 mm (P = 0.004) at 6 months. Up to 56% of the RDN-group patients achieved a target of less than 140/90 mmHg in the office BP; proportion of RDN-group patients with concentric left ventricular hypertrophy had decreased by 39%; mitral lateral E/E' ratio decreased from 14.8 ± 6.1 to 12.0 ± 3.2 (P = 0.016); isovolumic relaxation time shortened from 109.8 ± 16.2 to 100.8 ± 17.1 ms (P = 0.003); and N-terminal pro B-type natriuretic peptide levels reduced from 84.9 ± 35.9 to 57.2 ± 38.8 pg/ml (P < 0.001) significantly at 6 months post-RDN. Control patients exhibited no significant changes in all the above parameters (P > 0.05) at 6 months.. Multielectrode RDN contributes to improvement of diastolic dysfunction, reduction of left ventricular mass and attenuation of NT-proBNP, suggesting additional cardiovascular benefits in drug-resistant hypertension associated with left ventricular hypertrophy.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Denervation; Female; Heart Atria; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sympathectomy; Treatment Outcome; Ultrasonography

GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR).. Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment.. Plasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 h) or chronic (-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA1c, and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration.. Sustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endpoint Determination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Heart Rate; Humans; Hypertension; Liraglutide; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Receptors, Glucagon; Sodium

Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

Topics: Aged; Atorvastatin; Atrial Fibrillation; Cause of Death; Cholesterol; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors; Serum Albumin; Survival Rate; Troponin T; Uremia

Cardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood.. We measured high-sensitivity cardiac troponin I (hsTnI) in 12 956 and BNP in 11 076 participants without cardiovascular disease in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial before randomization to rosuvastatin 20 mg/d or placebo. Nearly 92% of participants had detectable circulating hsTnI, and 2.9% of men and 4.1% of women had levels above proposed sex-specific reference limits of 36 and 15 ng/L, respectively. hsTnI concentrations in the highest tertile were associated with a first major cardiovascular event (adjusted hazard ratio [aHR], 2.19; 95% confidence interval, 1.56-3.06; P for trend <0.001). BNP levels in the highest tertile were also associated a first cardiovascular event (aHR, 1.94; 95% confidence interval, 1.41-2.68; P for trend <0.001). The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02). Rosuvastatin was equally effective in preventing a first cardiovascular event across categories of hsTnI (aHR range, 0.50-0.60) and BNP (aHR range, 0.42-0.67) with no statistically significant evidence of interaction (P for interaction=0.53 and 0.20, respectively).. In a contemporary primary prevention population, baseline cardiac troponin I and BNP were associated with the risk of vascular events and all-cause mortality. The benefits of rosuvastatin were substantial and consistent regardless of baseline hsTnI or BNP concentrations.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Topics: Aged; Angina, Unstable; Biomarkers; Cholesterol, HDL; Comorbidity; Coronary Disease; Double-Blind Method; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Primary Prevention; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Stroke; Sulfonamides; Troponin T

Amino-terminal B-type natriuretic peptide (NT-proBNP) has been shown to predict postablation recurrences of atrial fibrillation (AF); however, given the associations of natriuretic peptides with various cardiovascular parameters potentially related to AF, whether the observed association with recurrence is truly an independent one is not clear.. The purpose of this analysis was to assess the association of NT-proBNP levels with AF recurrence after radiofrequency ablation.. This was a post hoc analysis of a prospective study of 296 hypertensive patients with symptomatic paroxysmal AF and no history of heart failure who were scheduled to undergo pulmonary vein isolation. NT-proBNP was measured at baseline, and patients were followed for a median of 13.7 months.. NT-proBNP levels at baseline were higher in patients with recurrence (269 pg/mL [199-361 pg/mL]) vs those who remained arrhythmia-free (188 pg/mL [146-320 pg/mL], P<.001). In a univariate Cox regression model, each higher quartile of NT-proBNP corresponded to a 47% (95% confidence interval 21.5%-77.9%) increase in the risk of recurrence. However, when baseline clinical AF burden, in terms of the number of clinical AF episodes in the previous year, was added to the model, the association of NT-proBNP lost its significance (adjusted hazard ratio 1.22, 95% confidence interval 0.94-1.57).. This is the largest series to date showing that NT-proBNP is a univariate predictor of postablation AF recurrence. However, it seems that adjustment for other covariates, including the number of AF episodes within the previous year, renders this association nonsignificant.

Topics: Aged; Atrial Fibrillation; Biomarkers; Catheter Ablation; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Prognosis; Proportional Hazards Models; Pulmonary Veins; Recurrence; Risk Assessment; Risk Factors

It remains uncertain whether diabetes itself causes specific echocardiographic features of myocardial morphology and function in the absence of hypertension or ischemic heart disease. The purpose of the present study was to determine the characteristics of pure diabetic cardiomyopathy-related echocardiographic morphology and function using layer-by-layer evaluation with myocardial strain echocardiography.. We enrolled 104 patients with poorly controlled type 2 diabetes mellitus (mean HbA1c level, 10%) with (n=74) or without (n=40) hypertension and 24 age- and sex-matched healthy volunteers. Patients with coronary artery stenosis or structural heart disease were excluded. Myocardial layer-specific strain was analyzed by speckle tracking echocardiography. Compared with the healthy control group, the normotensive diabetes group showed no significant difference in ejection fraction, left ventricular mass index, diastolic properties, left atrial volume index, or B-type natriuretic protein (BNP) level, but global longitudinal strain and subendocardial radial strain were significantly deteriorated. The deterioration of longitudinal strain correlated with body mass index (R=0.49, P<0.01) and blood pressure (R=0.36, P<0.01) in the normotensive diabetes group.. Deterioration of left ventricular longitudinal shortening accompanied by decreased subendocardial wall thickening are the characteristic functional abnormalities of diabetic cardiomyopathy in patients without hypertrophy, diastolic dysfunction, or elevated BNP. Obesity and blood pressure may also play important roles in this strain abnormality in asymptomatic patients with type 2 diabetes.

Topics: Adult; Aged; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Hypertension; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Obesity

Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF.. We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [o2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o2 peak. Secondary outcomes included tissue Doppler-derived E/e' at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg(-1)·min(-1); P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable.. Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573.

Topics: Aged; Aged, 80 and over; Asymptomatic Diseases; Benzazepines; Biomarkers; Cross-Over Studies; Cyclic Nucleotide-Gated Cation Channels; Double-Blind Method; Endpoint Determination; Exercise Test; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Hypertension; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Sinoatrial Node; Stroke Volume; Treatment Failure

Left ventricular hypertrophy and diastolic dysfunction (LVDD) remain highly frequent markers of cardiac damage and risk of progression to symptomatic heart failure, especially in resistant hypertension (RHTN). We have previously demonstrated that administration of sildenafil in hypertensive rats improves LVDD, restoring phosphodiesterase type 5 (PDE-5) inhibition in cardiac myocytes.. We hypothesized that the long-acting PDE-5 inhibitor tadalafil may be clinically useful in improving LVDD in RHTN independently of blood pressure (BP) reduction. A single blinded, placebo-controlled, crossover study enrolled 19 patients with both RHTN and LVDD. Firstly, subjects received tadalafil (20 mg) for 14 days and after a 2-week washout period, they received placebo orally for 14 days. Patients were evaluated by office BP and ambulatory BP monitoring (ABPM), endothelial function (FMD), echocardiography, plasma brain natriuretic peptide (BNP-32), cyclic guanosine monophosphate (cGMP) and nitrite levels.. No significant differences were detected in BP measurements. Remarkably, at least four echocardiographic parameters related with diastolic function improved accompanied by decrease in BNP-32 in tadalafil use. Although increasing cGMP, tadalafil did not change endothelial function or nitrites. There were no changes in those parameters after placebo.. The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.

Topics: Aged; Blood Pressure; Carbolines; Cross-Over Studies; Cyclic GMP; Diastole; Drug Resistance; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrites; Phosphodiesterase 5 Inhibitors; Single-Blind Method; Tadalafil; Ventricular Dysfunction, Left; Ventricular Function, Left

The aim of this study was to investigate the echocardiographic, biochemical short- and mid-term effects of the stenting procedure on left ventricular function, aortic stiffness, elasticity and systemic hypertension in children with coarctation of the aorta (CoA). Fifteen patients with native or recurrent CoA and 30 healthy controls who were sex and age matched were included in the study. The blood pressure values, echocardiographic measurements, elastic functions of ascending aorta and serum N-Terminal ProBNP (NT-ProBNP) levels were recorded prospectively before and at the first and sixth month after stenting. The mean arterial pressure recorded before stenting was 134.4±16.3 mm Hg; at the sixth month it was 115.5±9.5 mm Hg and in the control group it was 107.3±9.4 mm Hg. Although blood pressure levels were lower compared with the pre-stenting measurements (P<0.05), they were still significantly higher compared with the control group (P<0.05). Although a significant reduction was detected in the LVMIz at the end of the sixth month (50.4±14.3 g m(-2.7)) compared with the baseline (66.6±17.9 g m(-2.7); P<0.05), it was still higher compared with the control group (35.7±6.2 g m(-2.7); P<0.05). The baseline aortic elasticity (6.4±3.4 cm(2) dyn(-1) 10(-6)) was lower compared with the control group (10.0±1.7 cm(2) dyn(-1) 10(-6); P<0.05), and prestenting aortic stiffness was higher than that of the control group (5.6±1.6 dyn(-1) 10(-6); 2.5±0.45  dyn(-1) 10(-6); P<0.05). A statistically significant negative correlation was detected between the pressure gradient at the lesion site and aortic elasticity (r: -0.53, P: 0.04). Although resolution of the coarctation by endovascular stenting led to a reduction in the arteriopathy that had already begun before treatment, it was demonstrated that these children did not completely return to normal.

Topics: Adolescent; Angioplasty; Aorta; Aortic Coarctation; Blood Chemical Analysis; Blood Pressure Determination; Child; Child, Preschool; Double-Blind Method; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension; Male; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Reference Values; Statistics, Nonparametric; Stents; Time Factors; Vascular Stiffness

We investigated 3 hypotheses: (1) N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular disease events in patients with hypertension, (2) NT-proBNP is associated with blood pressure variability, and (3) NT-proBNP predicts benefit from antihypertensive regimens. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized a subset of 6549 patients at risk with no history of coronary heart disease to either atenolol-based or amlodipine-based blood pressure-lowering treatment. During 5.5 years of follow-up, 485 cardiovascular disease cases accrued and were matched with 1367 controls. Baseline and 6-month in-trial NT-proBNP were measured. The results show that NT-proBNP improves cardiovascular disease risk prediction beyond established predictors, continuous net reclassification improvement of 22.3% (P<0.0001). Furthermore, a 1-mm Hg increase in the SD of systolic blood pressure was associated with 2% higher baseline NT-proBNP in a multivariable regression analysis (P<0.0001). However, NT-proBNP predicted cardiovascular disease risk independently of blood pressure variation (odds ratio per SD increase in log NT-proBNP 1.24; 95% confidence interval, 1.06-1.45; P=0.007). Atenolol-based treatment led to a 69.6% increase in NT-proBNP at 6 months (P<0.0001). In contrast, amlodipine-based treatment reduced NT-proBNP by 36.5% (P<0.0001). Amlodipine recipients who achieved a 6-month NT-proBNP below the median (61 pg/mL) were at lower risk of cardiovascular disease when compared with those who did not (odds ratio, 0.58; 95% confidence interval, 0.37-0.91) after adjustment for confounders inclusive of baseline NT-proBNP and achieved blood pressure. If confirmed, these novel results suggest that NT-proBNP, as well as aiding cardiovascular disease risk assessment, may also help assess the efficacy of specific antihypertensive regimens. Further relevant studies seem warranted.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prevalence; Prognosis; Protein Precursors; Retrospective Studies; Risk Assessment; Risk Factors; Scandinavian and Nordic Countries; Time Factors; United Kingdom

A direct renin inhibitor (DRI), aliskiren, may be effective for blood pressure (BP) control in hemodialysis patients. However, it is unclear whether aliskiren has a greater beneficial effect on BP and humoral factors than angiotensin II receptor antagonists (ARBs) in hypertensive patients on hemodialysis.. Eighteen hemodialysis patients (58 ± 14 years) on the recommended dose of an ARB were prospectively randomized into two groups: ARB and DRI groups. Patients in the ARB group continued taking their previous ARB, whereas those in the DRI group switched to aliskiren (150 mg/day) for 12 weeks. Baseline measurements of BP and humoral factors such as plasma renin activity (PRA), plasma aldosterone concentration (PAC) and brain natriuretic peptide (BNP) were performed. Measurements were repeated every 4 weeks.. At baseline, no differences were observed in age, gender or BP between the two groups. Systolic BP was unaffected by treatment in either groups (group effect, p = 0.26; time effect, p = 0.38; group × time effect, p = 0.24). PRA decreased in DRI (p ≤ 0.02, group effect, p = 0.65; time effect, p = 0.13; group × time effect, p = 0.048), but not in ARB (p ≥ 0.94). PAC increased only in DRI (p ≤ 0.03), whereas BNP was unaffected in either group.. Aliskiren at a dose of 150 mg/day had a similar effect on BP compared with ARBs, but significantly lowered PRA.

Topics: Adult; Aged; Aldosterone; Amides; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Female; Fumarates; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Renin

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Arterial Pressure; Biphenyl Compounds; Catecholamines; Double-Blind Method; Female; Heart Rate; Heart Ventricles; Humans; Hypertension; Irbesartan; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Pulse Wave Analysis; Renal Dialysis; Tetrazoles; Vascular Stiffness

To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension.. A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment.. After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05).. In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Topics: Aged; Atorvastatin; C-Reactive Protein; Double-Blind Method; Endothelins; Exercise Tolerance; Female; Heart Failure; Heptanoic Acids; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyrroles

Although the cardiac biomarker B-type natriuretic peptide (BNP) is strongly related to mortality in end-stage renal disease (ESRD), whether it is a predictor of weight change or blood pressure (BP) response upon probing dry weight among hypertensive hemodialysis patients remains unknown. The purpose of this study was to examine among people with hypertension on hemodialysis whether BNP is a biomarker of excess volume.. Hypertensive hemodialysis patients (n = 150) were randomized to a control group (n = 50) or an ultrafiltration group (n = 100) and followed up for 30 dialysis treatments. After a baseline run-in of six treatments, those assigned to the ultrafiltration group had dry weight probed over 8 weeks. Forty-four-hour interdialytic ambulatory BP and predialysis BNP were measured at the end of run-in period, at 4 weeks and at 8 weeks.. The median BNP concentration was 93 pg/mL (interquartile range 31-257 pg/mL). The magnitude of decline in the BNP depended on the baseline concentration of BNP, but did not require probing dry weight or weight loss. No relationship existed between decline in postdialysis weight upon probing dry weight and baseline BNP. Furthermore, reduction in the BNP was not required for decline in postdialysis weight. Predialysis log BNP modestly predicted ambulatory systolic and pulse pressure independently of other risk factors. No relationship was found between decline in BP upon probing dry weight and baseline BNP. Upon probing dry weight, reduction in BNP was not required for decline in systolic ambulatory BP.. Taken together, these data suggest that among hypertensive patients on hemodialysis BNP is not a volume marker.

Topics: Adolescent; Adult; Biomarkers; Blood Pressure Monitoring, Ambulatory; Blood Volume; Body Weight; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Young Adult

Changes in the cardiovascular system with age may predispose older persons to development of heart failure with preserved ejection fraction. Vascular stiffening, aortic pressure augmentation, and ventricular-vascular coupling have been implicated. We explored the potential for acute reductions in late systolic pressure augmentation to impact left ventricular relaxation in older persons without heart failure.. Sixteen older persons free of known cardiovascular disease with the exception of hypertension had noninvasive tonometry and cardiac ultrasound to evaluate central augmentation index (AI) and diastolic function at baseline and after randomized, blinded administration of intravenous B-type natriuretic peptide (BNP) and hydralazine in a crossover design.. AI was significantly reduced after BNP (11.4±8.9 to -0.2±14.7%; P = 0.02) and nonsignificantly reduced after hydralazine (14.7±8.4% to 11.5±8.8%; P = 0.39). With decreased AI during BNP, a trend toward worsened myocardial relaxation by tissue Doppler imaging occurred (E' velocity pre- and post-BNP: 10.0±2.5 and 8.8±2.0cm/s, respectively; P = 0.06). There was a significant fall in stroke volume with BNP (68.5±18.3 to 60.9±18.1ml; P = 0.02), suggesting that changes in preload overwhelmed effects of afterload reduction on ventricular performance. With hydralazine, neither relaxation nor stroke volume changed.. Acute changes in late systolic aortic pressure augmentation do not necessarily lead to improved systolic or diastolic function in older people. Preload may be a more important determinant of cardiac performance than afterload in older people with compensated ventricular function. The potential for changes in preload to impair rather than enhance left ventricular systolic and diastolic function in older people warrants further study.. This study is registered at clinicaltrials.gov as NCT00204984.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Hydralazine; Hypertension; Infusions, Intravenous; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Stroke Volume; Systole; Treatment Outcome; Vascular Stiffness; Ventricular Function, Left

Elevated natriuretic peptide levels in asymptomatic individuals without heart failure are associated with increased risk of adverse cardiovascular outcomes and may reflect subclinical cardiac dysfunction.. In a sample of 313 asymptomatic individuals (51% women, mean age 61 years) with hypertension and diastolic dysfunction, we examined the association of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) with both conventional and advanced echocardiographic measures of systolic and diastolic function, including myocardial strain, using speckle-tracking-based analyses.. In univariate analyses, higher NT-proBNP was associated with greater left ventricular mass index (P = 0.003), left atrial volume index (P = 0.007), lateral E' velocity (P < 0.0001), E/E' ratio (P < 0.0001), peak global longitudinal systolic strain (P = 0.015), systolic strain rate (P = 0.021), and early diastolic strain rate (P < 0.0001). In multivariable analyses, NT-proBNP remained associated with measures of diastolic dysfunction, including lateral E' velocity (P = 0.013) and the E/E' ratio (P = 0.008). However, early diastolic strain rate was the echocardiographic parameter most strongly associated with NT-proBNP (P = 0.003).. In the setting of asymptomatic hypertensive heart disease and preserved ejection fraction, elevation in natriuretic peptide levels is predominantly associated with subclinical diastolic dysfunction.

Topics: Aged; Diastole; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Aim of this study was to compare the antiproteinuric effect of imidapril (I) and ramipril (R) in diabetic hypertensive patients with microalbuminuria.. One hundred and seventy-six patients were randomised to I 10 - 20 mg once daily (od) (n = 88) or R 5 - 10 mg od (n = 88) for 24 weeks. Clinic, ambulatory, central blood pressure (BP), urinary albumin excretion (UAE), plasma Angiotensin II (Ang II), bradykinin and brain natriuretic peptide (BNP) were assessed at baseline and after 6, 12 and 24 weeks.. Both I and R produced a similar decrease in clinic, ambulatory and central BP (p < 0.001 vs baseline). Both treatments significantly reduced UAE throughout the study, but the decrease in UAE associated with I was more pronounced, being evident at week 6 (p = 0.05) and maximal at week 24 end-point (-42 vs -29%, p < 0.01). BNP and Ang II levels were similarly reduced by I and R, while bradykinin increased more with R (+132 vs +86%, p < 0.05).. These findings showed that in diabetic hypertensive patients with microalbuminuria, despite equivalent BP-lowering effect, I produced a greater antiproteinuric effect than R, which might be due to different intrinsic molecular properties of the two drugs.

Topics: Adult; Aged; Albumins; Albuminuria; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Bradykinin; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ramipril; Treatment Outcome

The aim of this study was to compare the differences in the levels of a highly sensitive cardiac troponin T (Hs-cTnT) between Losartan (LOS) plus hydrochlorothiazide (HCTZ) and amlodipine. Seventy-eight hypertensive patients were randomized to receive LOS/HCTZ or amlodipine for 8 weeks. Both treatments decreased clinic and 24-hour blood pressure to the same extent. The Hs-cTnT level was significantly reduced in the amlodipine group (P < .05), but such a reduction was not found in the LOS/HCTZ group in the upper half group of Hs-cTnT level at baseline. Amlodipine had a more beneficial effect than LOS/HCTZ in patients with high Hs-cTnT levels.

Topics: Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; Blood Pressure; Calcium Channel Blockers; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Troponin T

High levels of plasma B-type natriuretic peptide (BNP) are associated with cardiac heart failure and death among patients on hemodialysis (HD). A recent study has demonstrated that the angiotensin II type 1 receptor blocker lowers BNP concentrations. Here, we examined whether the ability of olmesartan medoxomil (OM; a novel angiotensin II type 1 receptor blocker) to decrease plasma BNP levels is concentration dependent in hypertensive patients on HD.. This preliminary, observational, open-labeled prospective study included 24 patients on HD who were assigned to one group treated with OM (n = 14) or to an age-matched control group that was conventionally treated (n = 10). Blood pressure (BP) was monitored in the morning and evening of a non-HD day and before each HD session, and plasma BNP, plasma aldosterone (PAC), plasma active renin (PARC), and OM concentrations were measured at baseline, 4, and 8 weeks after treatment.. Plasma BNP levels were significantly decreased in the OM group, but remained unchanged in the control group after 4 and 8 weeks of treatment. Compared with the control group, OM was associated with increased PARC and decreased PAC levels. The OM concentrations at 4 and 8 weeks significantly correlated with depressed plasma BNP levels in accordance with multiple regression analysis adjusted for confounders including BP.. These results suggest that OM can help to decrease plasma BNP levels via a concentration-dependent effect in patients on HD.

Topics: Aged; Aged, 80 and over; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Female; Humans; Hypertension; Imidazoles; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Prospective Studies; Renal Dialysis; Renin; Tetrazoles

Although strict blood pressure (BP) control is effective in the prevention of cardiovascular events, it is often insufficient in many hypertensive patients. B-type natriuretic peptide (BNP) has been shown to be associated with cardiovascular events. We investigated the effects of the losartan/hydrochlorothiazide combination on BP and plasma BNP in hypertensive patients uncontrolled by an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB])-based therapy.. In a multicentre prospective observational study, we enrolled 185 patients aged 36-79 years (mean age 63.8 years) with essential hypertension but without symptoms of heart failure who received an ARB-based therapy for ≥3 months but failed to achieve a target BP recommended by the Japanese Society of Hypertension (JSH). ARBs were switched to losartan (LOS) 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg. The antihypertensive efficacy, safety, and effects of this combination on blood biochemical parameters and plasma BNP were evaluated for 12 months.. Mean ± SD systolic and diastolic BP decreased from 152 ± 13/87 ± 10 mmHg to 128 ± 14/74 ± 10 mmHg, respectively, after 12 months (p < 0.001). Mean ± SD plasma BNP levels decreased significantly from 46.0 ± 83.0 pg/mL to 40.8 ± 68.0 pg/mL (p < 0.05). The percentage of patients who achieved the JSH 2004 target BP was 51% after 12 months; the percentage was 63% in elderly patients aged ≥65 years without complications, and 43% in patients with concomitant diabetes mellitus or chronic kidney disease. No association was found between a decrease in plasma BNP levels and BP, age, body mass index or estimated glomerular filtration rate. There was a significant increase in serum uric acid and a decrease in serum potassium, but both were within the range of normal values. Adverse events were observed in 8.6% of the patients.. Antihypertensive treatment using two types of drugs (LOS/HCTZ) with different mechanisms yielded potent antihypertensive efficacy with safety and decreased plasma BNP levels.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.. We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2(CR), u-ENaC(β-CR)), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).. At baseline, no differences in u-AQP2(CR) or u-ENaC(β-CR) were measured between patients and controls. U-AQP2(CR) increased significantly more after saline in patients than controls, whereas u-ENaC(β-CR) increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2(CR) response.. No differences were found in u-AQP2(CR) and u-ENaC(β-CR) between patients and controls at baseline. However, in response to saline, u-AQP2(CR) was abnormally increased in patients, whereas the u-ENaC(β-CR) response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier: NCT00345124.

Topics: Adult; Aldosterone; Angiotensin II; Aquaporin 2; Atrial Natriuretic Factor; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Female; Glomerular Filtration Rate; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Osmolar Concentration; Renin; Sodium; Sodium, Dietary; Vasopressins

Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by ≥3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156±12/87±11 mmHg at baseline to 125±11/73±10 mmHg at 12 months (p<0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration ≥20 pg/mL, BNP decreased from 78.3±18.8 pg/mL to 57.3±17.7 pg/mL (p<0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diuretics; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Uric Acid

To determine advantages of therapy of functional class (FC) I-II chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction in patients with hypertensive disease (HD) with metoprolol succinate or quinapril and to assess their effect on regulatory-adaptive status.. Two hundred patients with I-II FC CHF and LVEF >50% at the background of stage I-II hypertensive disease participated in this study. They were randomized into 2 groups. Group I comprised 104 patients (mean age 52.8+1.9 years) who were prescribed metoprolol succinate 87.7+/-7.6 mg/day. Patients of group 2 (n=96, mean age 55.0+/-1.4 years) were prescribed quinapril 21.0+55 mg/day. Examination at baseline and after 6 months of therapy included 6 min walk test, treadmillometry with assessment of maximal oxygen consumptiion (VO2max), echocardiography, 24 hour blood pressure monitoring, measurement of N-terminal precursor of brain natriuretic peptide (NT-proBNP); test of cardio-respiratory synchronism was used for objective qualitative determination of the state of the ,renin-angiotensin system.. Both drugs improved parameters of LV diastolic function, but only quinapril effectively changed LV structural geometric parameters and systolic function. Only treatment with quinapril was associated with improvement of RAS, elevation of tolerance to physical effort, and increased VO2max. Quinapril more substantially lowered level of NT-proBNP.. Quinapril has an advantage over metoprolol succinate in therapy of patients with FC I-II CHF and preserved LF EF at the background of stage I-II HD.

Topics: Antihypertensive Agents; Biological Availability; Blood Pressure; Drug Monitoring; Female; Heart Failure; Humans; Hypertension; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quinapril; Renin-Angiotensin System; Stroke Volume; Tetrahydroisoquinolines; Treatment Outcome; Ventricular Function, Left

We recently demonstrated that pneumoperitoneum affects diastolic echocardiographic findings in healthy women scheduled for gynaecologic laparoscopy. No reports have been conducted in order to assess the echocardiographic consequences in hypertensive subjects during laparoscopic procedures.. The aim of this study was to evaluate Left Ventricular filling pressures in hypertensive women with and without diastolic dysfunction, combining the tissue Doppler imaging technique and the plasmatic levels of amino terminal proBNP.. Doppler recordings of mitral inflow, tissue Doppler imaging of mitral annulus and N-terminal-proBNP plasmatic levels were obtained in 40 hypertensive women with or without diastolic dysfunction. Measurements were executed in awake patients (T0), after the induction of anesthesia (T1), 10 and 20 minutes after the creation of the pneumoperitoneum (T2 and T3, respectively) and at the end of the surgery (T4). Furthermore, we collected the last blood sample after 12 hours (T5).. The E/Ea ratio for the evaluation of left ventricular filling pressures were higher in the diastolic dysfunction group than in the non diastolic dysfunction and significantly increased after pneumoperitoneum. Pneumoperitoneum increased the plasmatic levels of natriuretic peptide in both groups. At the end of the procedure we did not observe any further significant alteration.. Pneumoperitoneum produces a consistent increase of ventricular filling pressures in a population of hypertensive patients with and without diastolic dysfunction. Moreover, there is a significant but transient rise in NT-proBNP after gas insufflation in both groups, most accentuated in the diastolic dysfunction group.

Topics: Adult; Echocardiography, Doppler; Female; Humans; Hypertension; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pneumoperitoneum, Artificial; Ventricular Dysfunction, Left

According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7±9.5 pmol l⁻¹) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P=0.004), while independent predictor of the β-stiffness of carotid artery was the urinary EO (P=0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure Monitoring, Ambulatory; Carotid Artery, Common; Catecholamines; Chronic Disease; Circadian Rhythm; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Ouabain; Peptide Fragments; Risk Factors

Patients with atrial fibrillation (AF) and atrial thrombus are at high risk of thromboembolic events. We investigated whether BNP levels can serve as a biological marker of thrombus.. We prospectively enrolled patients with AF within 7days of an ischemic stroke and transient ischemic attack (TIA). We measured BNP levels in all patients while they underwent transesophageal echocardiography (TEE) and then assigned them to groups based on the presence (positive group) or absence (negative group) of left atrial thrombus. Factors associated with atrial thrombus were investigated using multivariate logistic regression analysis.. Of the 67 (male, n = 40; mean age, 76.5 ± 11.1 years) enrolled patients, 17 (25.4%) had left atrial thrombus. The incidence of hypertension was significantly higher in the positive, than in the negative group (88.2% vs. 58.0%, p = 0.020). The BNP level was also significantly higher in the positive, than in the negative group (median (interquartile range) 189.8 (141.4-473.2) vs. 117.9 (70.3-187.1) pg/ml, p=0.012). The optimal cut-off value, sensitivity, and specificity of BNP levels to distinguish the positive, from the negative group were 140.0 pg/ml, 76.5%, and 62.0%, respectively. Multivariate logistic regression analysis demonstrated that a BNP concentration of>140.0 pg/ml (odds ratio, 5.62; 95% CI, 1.39-22.66, p = 0.015) was an independent factor associated with thrombus.. Levels of BNP can serve as a marker of left atrial thrombus in acute ischemic stroke and TIA in patients with AF.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Comorbidity; Echocardiography, Transesophageal; Female; Heart Atria; Humans; Hypertension; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Factors; Sensitivity and Specificity; Thrombosis

Angiotensin II type 1 (AT1) receptor antagonists (angiotensin receptor blockers [ARBs]) are widely used for the treatment of not only hypertension but also cardiac dysfunction. B-type natriuretic peptide (BNP) is secreted mainly by the cardiac ventricle and plays an important role in the regulation of blood pressure (BP) and body fluid. It has been established that the plasma level of BNP is increased in patients with chronic heart failure in proportion to the severity of cardiac dysfunction. Because cardiac dysfunction is closely associated with a high risk of mortality in patients with diabetes mellitus, early identification and prevention of cardiac dysfunction are important. The objective of this study was to determine the effects of olmesartan medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with type 2 diabetes.. This was a preliminary, prospective, observational, open-label study. Sixty-eight type 2 diabetic patients with hypertension (systolic BP [SBP]≥140 mmHg or diastolic BP [DBP]≥90 mmHg) received olmesartan medoxomil 10–20 mg/day for 24 weeks. Plasma levels of BNP, as well as several clinical parameters of glycaemic control and lipid metabolism, were compared before and after 24 weeks of treatment. Another group consisting of 22 age- and body mass index-matched subjects not treated with olmesartan medoxomil was observed for reference purposes.. In the olmesartan medoxomil group, mean±SD SBP decreased from 152.8±16.4 at baseline to 146.8±14.4 mmHg after 24 weeks' treatment (p<0.05); similarly, mean±SD DBP decreased from 85.6±10.5 to 81.3±11.6 mmHg (p<0.05). In 53 subjects in whom plasma levels of BNP could be measured both before and after treatment, mean±SD BNP decreased from 41.3±49.9 to 32.5±36.3 pg/mL (p<0.05). Change in plasma BNP level over the 24-week treatment period in the olmesartan medoxomil group was not correlated with change in SBP or DBP. Multiple regression analysis revealed that change in plasma BNP level was not correlated with baseline value of or change in any other parameters. No other parameters in the olmesartan medoxomil group, and no parameters in the non-olmesartan medoxomil reference group, showed significant changes.. The current preliminary study showed that olmesartan medoxomil treatment might decrease plasma BNP levels, independent of its BP-lowering effect, in hypertensive patients with type 2 diabetes.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Prospective Studies; Tetrazoles

In spite of appropriate pharmacologic therapy, many hypertensive patients develop an abnormal left ventricular relaxation with preserved systolic function. This cardiac dysfunction increases the risk of cardiovascular complications. The authors assessed the therapeutic effects of an intervention with exercise training and weight reduction in patients with pharmacologically well-treated hypertension who had abnormal left ventricular relaxation with normal systolic function. Eighty-eight (44%) of 202 medically treated hypertensive patients had abnormal ventricular relaxation with normal ejection fraction. These patients were randomized to either a 6-month intervention program (cycle ergometer training twice a day for 5 days a week and a hypocaloric diet) or a control program (unchanged pharmacologic therapy without exercise and diet. Body weight, blood pressure, New York Heart Association class, glomerular filtration rate, and exercise capacity and workload were measured. Cardiac function was assessed by measuring N-terminal pro-B-type natriuretic peptide values, the electrocardiographic QT dispersion interval, and echocardiography (left atrial size, Doppler-derived E/A ratio, and mitral deceleration time). Physical exercise with weight reduction reduced blood pressure, decreased cardiovascular risks, and improved abnormal left ventricular relaxation. Measuring left atrial size is the best method for assessing changes in left ventricular relaxation with preserved systolic function.

Topics: Antihypertensive Agents; Blood Pressure; Body Weight; Diet, Reducing; Electrocardiography; Exercise; Exercise Therapy; Exercise Tolerance; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function, Left; Weight Loss

Topics: Adrenergic alpha-1 Receptor Antagonists; Albuminuria; Doxazosin; Humans; Hypertension; Natriuretic Peptide, Brain; Prospective Studies

The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) showed that an amlodipine-based regimen prevented more cardiovascular events than an atenolol-based regimen in patients at high risk of hypertension.The basis of this difference is partly unknown and may be due to their divergent effects on the remodelling process of hypertensive heart disease.. We measured plasma levels of aminoterminal propeptide of atrial natriuretic peptide (NT-proANP) and aminoterminal propeptide of B-type natriuretic peptide and serum levels of the aminoterminal propeptide of type I procollagen (PINP), aminoterminal propeptide of type III procollagen and type I collagen telopeptide in 93 patients randomized in the ASCOT study at baseline and after two and four years and compared them with echocardiographic parameters and blood pressure. NT-proANP decreased at two years by 22 (-484 - 153) pmol/l in the amlodipine-based regimen and increased by 109 (-297 - 1545) pmol/l in the atenolol-based regimen (P < 0.001), whereas no significant difference in NT-proBNP between the arms was found. PINP levels increased by 1.8 (-29 -31) microg/l in the amlodipine-based regimen and decreased by 4.7 (-27- 31) microg/I in the atenolol-based regimen, whereas no differences were found in other collagen markers between the arms. Major echocardiographic changes were not found.. Our results show that the two treatment regimens of ASCOT-BPLA had different effects on plasma natriuretic peptides and serological markers of collagen turnover, probably reflecting divergent effects in cardiac remodelling.

Topics: Amlodipine; Antihypertensive Agents; Atenolol; Atrial Natriuretic Factor; Biomarkers; Collagen; Collagen Type I; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Procollagen; Ventricular Remodeling

Aim of the study - to determine efficacy of therapy with the use of ivabradine in patients with functional class (FC) III chronic heart failure (CHF) on the basis of assessment of its action on regulatory adaptive status (RAS). We included into the study 100 patients with FC III CHF at the background of ischemic heart disease (IHD) and/or stage III hypertensive disease (HD) receiving complex therapy (quinapril, torasemide, spironolactone). After randomization group 1 comprised 56 patients (age 62.9+/-1.8 years) who were prescribed slow release metoprolol succinate (59.1+/-4.5 mg/day). Group 2 comprised 44 patients (age 59.4+/-1.3 years) who were prescribed If channel inhibitor ivabradine (12.1+/-2.3 mg/day) if beta-blocker use was not possible. Examination at baseline and in 6 months included treadmillometry with assessment of maximal oxygen consumption (VO2 max) at exercise, echocardiography, 24-hour blood pressure monitoring, measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood plasma. For objective qualitative assessment of the state of RAS we used a test of cardio-respiratory synchronism. Therapy with the use of ivabradine improved structural and functional state of the myocardium, elevated tolerance to exercise, caused positive changes of NT-proBNP concentration in blood plasma and VO2 max at exercise. Thus ivabradine probably can serve as alternative to -adrenoblockers when their use is not possible patients with FC III CHF at the background of IHD and/or stage III HD.

Topics: Benzazepines; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Agents; Chronic Disease; Drug Monitoring; Drug Therapy, Combination; Echocardiography; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Hypertension; Ivabradine; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Severity of Illness Index; Treatment Outcome

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme 2; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Tetrazoles

To compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction.. 97 patients with a systolic blood pressure (SBP) > or =140 mmHg, a left ventricular ejection fraction >0.50, and echocardiographic evidence of diastolic dysfunction were randomly assignment to open-label treatment with eprosartan (with other anti-hypertensives; n = 47) or other anti-hypertensives alone (n = 50). Echocardiography, including tissue Doppler imaging (TDI), and neurohormones were done at baseline and after 6 months.. Mean age was 65 (+/-10) years and 64% was female. During 6 months of treatment, SBP decreased from 157 +/- 16 to 145 +/- 18 mmHg in the eprosartan group and from 158 +/- 17 to 141 +/- 18 mmHg in the control group (both p < 0.001; p = ns between groups). Diastolic function was unaffected in both groups and there was no correlation between changes in SBP and changes in mean TDI (r = -0.06; p = 0.58). Aldosterone levels decreased in the eprosartan group, but other neurohormones remained largely unchanged. Change in SBP was however related to the change in NT-proBNP (r = 0.26; p = 0.019).. Lowering blood pressure, either with eprosartan or other anti-hypertensives in hypertensive patients with diastolic dysfunction did not change diastolic function after 6 months of treatment, but was associated with a decrease of NT-proBNP.

Topics: Acrylates; Aged; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diastole; Echocardiography; Female; Heart; Humans; Hypertension; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Peptide Fragments; Peptidyl-Dipeptidase A; Stroke Volume; Thiophenes; Treatment Outcome; Ventricular Dysfunction; Ventricular Function; Ventricular Function, Left

Several traditional cardiovascular risk factors assessed in the middle-aged are associated with the risk of dementia, but they are known to lose much of their prognostic value when measured in the elderly. The aim of the study was to compare B-type natriuretic peptide (BNP) with previously known risk markers for dementia in their association with cognitive decline and dementia during a follow-up.. A total of 464 subjects free of dementia aged 75 years or more were examined and followed up for 5 years in a prospective population-based stratified cohort study. The association of clinical variables to base-line Mini Mental State Examination score (MMSE), the decline of MMSE, and onset of dementia during the follow-up were examined.. The only variable to significantly associate with the decline of MMSE was BNP (beta 0.140; P = 0.019). A total of 59 new cases of dementia were diagnosed after the follow-up. Significant predictors of the occurrence of dementia over the study period were BNP (adjusted odds ratio (OR) 1.53; 95% confidence interval (CI) 1.09-2.16; P = 0.013), length of education (OR 0.50; 95% CI 0.33-0.77; P = 0.001), and diagnosis of hypertension (OR 0.53; 95% CI 0.27-0.95; P = 0.036). BNP remained as a significant predictor of dementia and the decline of MMSE even after adjustment to the base-line MMSE.. BNP is an independent harbinger of the cognitive decline and incidence of new onset of dementia in an elderly general population. This is a ground for testing the impact of antihypertensive treatment in the prevention of cognitive impairment in those with elevated BNP.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Cohort Studies; Dementia; Educational Status; Female; Finland; Follow-Up Studies; Humans; Hypertension; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors

Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension.. In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension.. Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals.. Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.. ClinicalTrial.gov NCT01090752. Hypertension Research Foundation Lausanne.

Topics: Analysis of Variance; Blood Pressure; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypertension; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Natriuretic Peptide, Brain; Pioglitazone; Sodium, Dietary; Thiazolidinediones

This study investigated whether wave reflection measured by wave intensity analysis predicts future cardiovascular events in individuals with hypertension and sought to establish whether this relationship is independent of other cardiovascular risk factors and is associated with evidence of increased load on the left ventricle.. Wave reflection may impose an additional load on the left ventricle, and augmentation index, a surrogate of wave reflection, has been reported to predict cardiovascular events in some, but not all studies.. Measurements of brachial and carotid blood pressure (BP) measurement, carotid ultrasound, echocardiography, and blood chemistry analyses were performed on 259 ASCOT (Anglo Scandinavian Cardiac Outcomes Trial) participants approximately 1 year after randomization, and wave intensity analysis was used to calculate wave reflection index (WRI), the ratio of peak forward to peak backward pressure (P(b)/P(f)), and carotid augmentation index (cAI(x)). All participants were followed up for a median period of 5.9 years, accruing 33 cardiovascular events.. WRI, P(b)/P(f), and to a lesser extent, cAI(x), were correlated. WRI predicted cardiovascular events (hazard ratio: 2.10; 95% confidence interval: 1.10 to 3.99; p = 0.02) in an unadjusted model. Multivariate analysis showed that this association was independent of BP. P(b)/P(f) and cAI(x) did not significantly predict cardiovascular events. WRI was also positively associated with increased left ventricular mass index and elevated B-type natriuretic peptide adjusted for age and sex, and these associations were independent of BP or other cardiovascular risk factors.. Higher wave reflection predicts future cardiovascular events independent of conventional risk factors in people with treated hypertension.

Topics: Aged; Blood Pressure; Cardiovascular Diseases; Female; Heart Ventricles; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Risk Factors

The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA).. In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA.. BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml(-1) (interquartile range (IQR) 35-250) and decreased significantly within 1 day of PTRA to 62 pg ml(-1) (IQR 24-182) (p < 0.001), remaining at 75 pg ml(-1) (IQR 31-190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46-0.67). Pre-intervention BNP >50 pg ml(-1) was seen in 79% of patients with BP improvement compared with 56% in patients without improvement (p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml(-1) was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2-13.2).. BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml(-1) may be helpful to identify patients in whom PTRA will improve BP.

Topics: Aged; Angioplasty; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Renal Artery Obstruction; Stents

Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether an angiotensin II type 1 receptor blocker losartan would improve ambulatory short-term BP variability in hypertensive patients on hemodialysis.. Forty hypertensive patients on hemodialysis therapy were randomly assigned to the losartan treatment group (n=20) or the control treatment group (n=20). At baseline and 6 and 12 months after the treatment, 24-h ambulatory BP monitoring was performed. Echocardiography and measurements of brachial-ankle pulse wave velocity (baPWV) and biochemical parameters were also performed before and after therapy.. After 6- and 12-months of treatment, nighttime short-term BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased in the losartan group, but remained unchanged in the control group. Compared with the control group, losartan significantly decreased left ventricular mass index (LVMI), baPWV, and the plasma levels of brain natriuretic peptide and advanced glycation end products (AGE). Furthermore, multiple regression analysis showed significant correlations between changes in LVMI and changes in nighttime short-term BP variability, as well as between changes in LVMI and changes in the plasma levels of AGE.. These results suggest that losartan is beneficial for the suppression of pathological cardiovascular remodeling though its inhibitory effect on ambulatory short-term BP variability during nighttime.

Topics: Adiponectin; Aged; Angiotensin II Type 1 Receptor Blockers; Ankle; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brachial Artery; Circadian Rhythm; Female; Glycation End Products, Advanced; Humans; Hypertension; Hypertrophy, Left Ventricular; Lipoproteins, LDL; Losartan; Male; Malondialdehyde; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; Renal Dialysis; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Remodeling

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day(-1)) was changed to efonidipine at a dose of 40 mg day(-1)). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121+/-25 vs. 114+/-21 g m(-2), P<0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.

Topics: Aged; Aldosterone; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrophenols; Organophosphorus Compounds; Renin; Time Factors

This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension.. This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age > 18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90-109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90-99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100-109 mm Hg) for the first 4 weeks. If SiDBP was > or = 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP < 90 mm Hg and SiSBP < 140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks).. The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P < 0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P < 0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (-63.8 and -38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]).. There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8.

Topics: Antihypertensive Agents; Blood Pressure; C-Reactive Protein; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Administration Schedule; Drugs, Generic; Female; Humans; Hydrochlorothiazide; Hypertension; Korea; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ramipril; Severity of Illness Index; Treatment Outcome; Ventricular Function, Left

Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours x 7 days) and high sodium diets (250 mmol/24 hours x 7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4+/-0.5 antihypertensive medications with a mean office BP of 145.8+/-10.8/83.9+/-11.2 mm Hg. Mean urinary sodium excretion was 46.1+/-26.8 versus 252.2+/-64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension.

Topics: Adult; Aged; Aldosterone; Blood Pressure; Body Mass Index; Creatinine; Cross-Over Studies; Diet, Sodium-Restricted; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Potassium; Renin; Sodium; Sodium, Dietary; Time Factors

We investigated the impact of lowering blood pressure (BP) with azelnidipine, a newly developed calcium channel blocker, generation on the left ventricular (LV) diastolic function and LV filling pressure by assessing non-invasive indices derived from echo Doppler study. This study evaluated 232 hypertensive patients with diastolic dysfunction. This study had two groups: (1) in which azelnidipine was administered to patients as a first-line therapy, and (2) in which amlodipine was converted to azelnidipine. Early diastolic mitral annulus velocity (e', cm s(-1)), the ratio of peak E velocity to e' velocity (E/e' ratio) and level of brain natriuretic peptide (BNP) were measured before and, an average of, 8 months after azelnidipine treatment. In the first-line azelnidipine group, the systolic and diastolic BP reduced by 26 and 11 mm Hg, respectively. The e' increased, and E/e' ratio and BNP level decreased significantly. In the converted-from-amlodipine group, the systolic and diastolic BP decreased by 14 and 6 mmHg, respectively. The e' velocity increased, but the E/e' ratio and BNP level did not change. In both groups, azelnidipine lowered BP and improved LV diastolic function (an increase in the e' velocity). Possible reduction in LV filling pressure (a decrease in the E/e' ratio and BNP level) is observed only in the first-line azelnidipine group.

Topics: Adult; Aged; Aged, 80 and over; Azetidinecarboxylic Acid; Calcium Channel Blockers; Dihydropyridines; Drug Therapy, Combination; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

Topics: Adult; Albuminuria; Aldosterone; Antihypertensive Agents; Asian People; Blood Pressure; Cross-Over Studies; Diabetes Complications; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Renin; Tablets; Treatment Outcome

Doxazosin is reported to increase the incidence of congestive heart failure. The benefits of doxazosin, for controlling morning blood pressure as well as its effect on the left ventricular structure and function, are herein examined.. In this study, 223 morning hypertensive patients were randomized into either the doxazosin group, with a once-daily bedtime dose of doxazosin, or the control group, who continued their current medication. Atenolol was added to the doxazosin group when needed. The effect of doxazosin was evaluated by measurement of echocardiographic parameters and B-type natriuretic peptide.. The left ventricular wall thickness decreased, but the left ventricular diastolic diameter in the doxazosin group increased from the baseline. The changes in the left ventricular mass index were similar between the groups, whereas the relative wall thickness in the doxazosin group decreased more than that in the control group. The left ventricular diastolic function could deteriorate in the doxazosin group. In the doxazosin group, an increase in the left ventricular diameter was only seen in the patient who did not take diuretics throughout the study. The office and home blood pressure in the doxazosin group decreased more than that in the control group, whereas the B-type natriuretic peptide increased in the doxazosin group. Three cases of congestive heart failure were observed in the doxazosin group, but none in the control group.. Although a bedtime dose of doxazosin can significantly lower the blood pressure, it can also increase left ventricular diameter, thus increasing the risk of congestive heart failure. However, the prior use of diuretics can prevent the unfavorable effects of doxazosin on the left ventricular structure.

Topics: Aged; Antihypertensive Agents; Circadian Rhythm; Doxazosin; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left

Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level.

Topics: Albuminuria; Amlodipine; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Calcium Channel Blockers; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypertension; Japan; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

We compared the effects of telmisartan and olmesartan in 20 patients with chronic heart failure and metabolic syndrome. The subjects underwent once-daily 40 mg telmisartan for at least 3 months before switching to once-daily 20 mg olmesartan for the next 3 months (post 1). They were then treated with 3 months of once-daily 40 mg telmisartan (post 2). Systolic and diastolic blood pressure in the early morning, plasma B-type natriuretic peptide, serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were increased at post 1 (p < 0.005, p < 0.05, p < 0.05, p < 0.05, p < 0.05, and p < 0.005 vs. baseline, respectively) before returning to their baseline values at post 2. The changes in plasma B-type natriuretic peptide levels correlated significantly with the shifts in systolic and diastolic blood pressure in the early morning at posts 1 and 2. Meanwhile, there were no fluctuations in either blood pressure in the late evening or in the outpatient room; nor were there fluctuations in heart rate. Simultaneously, neither serum high-density lipoprotein cholesterol nor fasting blood sugar levels differed significantly between posts. Moreover, telmisartan had more beneficial effects on glucose and lipid profiles in patients with relatively high HbA1c, serum total and low-density lipoprotein cholesterol, and triglyceride levels. Therefore, we concluded that telmisartan was more beneficial than olmesartan for controlling blood pressure in the early morning, as well as for improving glucose and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Glucose; Blood Pressure; Chronic Disease; Female; Glycated Hemoglobin; Heart Failure; Heart Rate; Humans; Hypertension; Imidazoles; Lipid Metabolism; Lipids; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Telmisartan; Tetrazoles

Lowering of the central pulse pressure (PP) has been shown to contribute to an improvement of the cardiac damage beyond that of lowering the brachial PP. We assessed the hypothesis that the change in the central PP is more useful than that in the brachial PP in the assessment of the change in cardiac load.. We studied 434 treated hypertensive patients whose home systolic blood pressure was 135 mmHg or higher. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin 1-4 mg and atenolol when needed). We measured the brachial and central (carotid) blood pressure simultaneously using a validated device, and the B-type natriuretic peptide at baseline and at the sixth month of treatment.. In the added treatment group, the brachial systolic blood pressure was successfully reduced, but the central PP increased significantly, whereas the other blood pressure parameters did not change from the baseline. In the added treatment group, the change in the B-type natriuretic peptide was significantly correlated with the change in the brachial PP (r = 0.18), central systolic blood pressure (r = 0.18), central PP (r = 0.26), and PP amplification (r = -0.22) even after adjusting for the confounding factors. The correlation with the central PP was stronger than with the brachial PP (P = 0.018) or central systolic blood pressure (P = 0.002), and these relationships were essentially the same even after adjustment for the use of atenolol or the change in heart rate.. This study showed that the central PP measurement may be more important to assess cardiac load than the brachial PP during antiadrenergic treatment.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Atenolol; Biomarkers; Blood Pressure; Blood Pressure Determination; Brachial Artery; Carotid Arteries; Case-Control Studies; Doxazosin; Drug Therapy, Combination; Female; Humans; Hypertension; Japan; Male; Middle Aged; Natriuretic Peptide, Brain

Orthostatic blood pressure (BP) dysregulation is a risk factor for both falls and cardiovascular events. Self-measured BP, carried out at home, is both highly reproducible and useful for evaluating antihypertensive treatment. However, there have been a few reports on the clinical implications of orthostatic BP changes in home BP monitoring (HBPM). In the baseline examination for the Japan Morning Surge-1 Study, a multicenter randomized control trial, we evaluated 605 hypertensive outpatients who had a morning systolic BP above 135 mmHg. The plasma brain natriuretic peptide (BNP) level and urinary albumin excretion were measured. When the patients were divided into 10 groups, according to orthostatic BP change evaluated by HBPM, after adjusting for age, gender, body mass index and sitting home BP level, those in the top decile (n=60, orthostatic BP increase>7.8 mmHg) had a higher urinary albumin/creatinine ratio (UAR) than the lowest decile group (geometric mean [SEM range]: 209.1 [134.7-318.7] vs. 34.1 [20.1-56.2] mg/g creatinine [Cr], p=0.003) and the pooled second to ninth decile groups (n=485, 209.1 [134.7-318.7] vs. 39.7 [33.2-47.3] mg/g Cr, p<0.02). Additionally, patients in the top decile had a higher BNP level than the second to ninth decile groups (75.7 [55.0-103.1] vs. 23.6 [20.8-26.6] pg/mL, p=0.003). Evaluation of orthostatic hypertension at home might be a high-risk factor for cardiovascular events in hypertensive subjects with increased levels of BNP and a higher UAR, independent of the home sitting BP level.

Topics: Aged; Aged, 80 and over; Aging; Albuminuria; Antihypertensive Agents; Autonomic Nervous System Diseases; Blood Pressure Monitoring, Ambulatory; Creatinine; Doxazosin; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Posture; Risk Factors

Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure.. Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration >100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and beta-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients' mean age was 68 years, mean ejection fraction was 31%, and mean+/-SD systolic blood pressure was 129+/-17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762+/-6123 pg/mL with placebo and fell by 244+/-2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo.. Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and beta-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Aged; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; Female; Fumarates; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Severity of Illness Index; Treatment Outcome

We evaluated whether morning minus evening systolic blood pressure (SBP) difference (MEdif) in home blood pressure measurements can be a marker for hypertensive target organ damage. The authors analyzed 611 hypertensive patients who had high morning SBP levels (>/=135 mm Hg). The patients with morning hypertension (MEdif >/=15 mm Hg, average of morning and evening SBP [MEave] >/=135 mm Hg) were older (P<.001) and had a longer duration of hypertension and antihypertensive medication use, a higher prevalence of left ventricular hypertrophy (LVH) on electrocardiography, a lower glomerular filtration rate by the Cockcroft-Gault equation (P=.002), and a higher brain natriuretic peptide (BNP) level (P<.001) than those with well-controlled blood pressure (MEdif <15 mm Hg, MEave <135 mm Hg). The patients with morning hypertension had a higher BNP level than those with well-controlled blood pressure after adjustment for the confounding factors (28.7 pg/mL vs 20.0 pg/mL; P=.033). In conclusion, morning hypertension is more likely seen among patients with older age and longer duration of hypertension and antihypertensive medication use, and it may be associated with a higher prevalence of LVH and a higher BNP level.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Female; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Systole

Acutely decompensated congestive heart failure is a major cause of emergency department (ED) visits in county hospitals. This often underserved population has a high rate of return visits to the ED for heart failure. Nesiritide has been demonstrated to relieve symptoms of acutely decompensated congestive heart failure. We examined the effect of an 8-hour infusion of nesiritide on the composite of return to the ED or hospitalization at 30 days.. A prospective, randomized, double-blinded, placebo-controlled trial of nesiritide plus protocol-specified standard therapy versus standard therapy done in the ED for acutely decompensated congestive heart failure.. One hundred one patients were randomized during a 16-month enrollment period. Sixty-six percent of the patients were men and 34% were women. Fifty-six percent were black; all patients had New York Heart Association class II to IV heart failure and most had dyspnea at rest or with minimal exertion. Complete follow-up data were available in 97 of 101 patients. After the 8-hour treatment period, acute symptom relief was experienced in 95.7% of the nesiritide group (95% confidence interval [CI] 88.9% to 100%) versus 86.8% of the placebo group (95% CI 72% to 98.9%), with an absolute difference between the 2 groups of 8.9% (95% CI -3.3% to 24.2%). Diuresis was similar between the 2 groups, but hypotension occurred more frequently in the nesiritide-treated group. The primary outcome measure of return visit to the ED or hospitalization at 30 days was higher for nesiritide (41.5%) than placebo (39.6%; absolute difference 1.9%; 95% CI -17.2% to 21.1%). There was only 1 death. No measurable change in renal function was observed.. Administration of nesiritide for acutely decompensated congestive heart failure in a county ED was no better than standard therapy alone for return to the ED or hospitalization at 30 days.

Topics: Emergency Service, Hospital; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Recurrence

Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones.. We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography.. There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol.. Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.

Topics: Aged; Aldosterone; Angiotensin II; Blood Glucose; Blood Pressure; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Endothelium, Vascular; Female; Fibroblast Growth Factors; Glycated Hemoglobin; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain

In essential hypertension (ESS) whole body and vascular nitric oxide (NO) synthesis is generally thought to be reduced. We therefore investigated the systemic and renal responses to acute treatment with N(G)-monomethyl-l-arginine (L-NMMA), a competitive NOS-inhibitor, in 12 patients with ESS and 18 healthy controls (CON) in a randomized, placebo-controlled study. Main effect parameters were renal hemodynamics (glomerular filtration rate [GFR] and renal plasma flow [RPF]), systemic blood pressure (BP), and fractional excretions of sodium (FE(Na)) and lithium (FE(Li)). Experiments were performed on two occasions for each subject studying the effects of either L-NMMA (3 mg/kg intravenously) or placebo. The patients with ESS were studied after at least 14 days off antihypertensive medication. Renal hemodynamics were assessed by the clearances of (125)I-hippuran (RPF) and (51)Cr-EDTA (GFR). The L-NMMA induced a significant increase in systemic BP and significant reductions in RPF, FE(Na), and FE(Li) in both groups. The increase in diastolic BP was significantly attenuated in ESS (ESS: 8% +/- 2% v CON: 14% +/- 2%, P < .05). The GFR and RPF were equally reduced by L-NMMA in both groups (RPF(ESS): -19% +/- 4% v RPF(CON): -15% +/- 3%, P = not significant [NS]). However, the reduction in FE(Na) was enhanced in ESS (ESS: -42% +/- 7% v CON: -25% +/- 3%, P < .01). The FE(Li) decreased equally in both groups (ESS: -17% +/- 2% v CON: -17% +/- 6%, P = NS). It is concluded that acute NO blockade in ESS is accompanied by a reduced systemic pressor response, an unchanged renal hemodynamic response, and an enhanced reduction in FE(Na). The results suggest that patients with essential hypertension are highly dependent on NO to maintain sodium excretion.

Topics: Administration, Oral; Adult; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Cyclic GMP; Enzyme Inhibitors; Female; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Lithium; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Renal Circulation; Renin-Angiotensin System; Sodium; Sodium Chloride; Time Factors

We attempted to test the hypothesis that chronic angiotensin II type 1A receptor blockade (ARB) alters myocardial collagen turnover leading to an improvement of diastolic dysfunction in diabetic patients.. Forty-eight type 2 diabetic patients were divided into 2 groups: 38 treated with candesartan for 6 months, and 10 without candesartan, as controls. Doppler mitral flow velocity pattern and biomarkers of collagen type I turnover were assessed before and after ARB during a 6-month period. The mitral E/A ratio increased from 0.65+/-0.11 to 0.75+/-0.19. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, decreased and the carboxy-terminal telopeptide of collagen type I (CITP), an index of collagen type I degradation, increased following ARB. Consequently, the PIP/CITP ratio, an index of coupling between the synthesis and degradation of collagen type I, decreased. None of the indexes changed in the control group. The change in left ventricular chamber stiffness did not correlate with the change in PICP (r=0.08, p=NS), but it did with the changes in CITP or in the PIP/CITP ratio (r=0.35, p<0.05; r=0.39, p<0.05).. Chronic ARB improves diastolic dysfunction in diabetic patients, at least partially through the attenuation of myocardial fibrosis, by regulating collagen turnover, particularly by facilitating collagen degradation.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Collagen; Diabetes Mellitus, Type 2; Endomyocardial Fibrosis; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles; Ventricular Dysfunction, Left

B-type natriuretic peptide (BNP) has been largely validated in the etiologic diagnosis of acute dyspnea. Nevertheless, its reliability in the setting of a preserved left ventricular systolic function (ejection fraction >50%) has not been adequately established.. the study addressed the usefulness of BNP in the diagnosis of new-onset heart failure with a preserved systolic function in hypertensive patients hospitalized for acute dyspnea.. 59 consecutive hypertensive patients without history of heart failure and coronary disease were included. BNP was measured at presentation with the Triage system. Noninvasive estimation of left ventricular filling pressures by bedside tissue Doppler echocardiography at presentation was incorporated in the diagnostic criteria.. the 30 patients with heart failure were not significantly different from the 29 patients with noncardiac cause of acute dyspnea regarding age, gender, body mass index and ejection fraction. Median levels of BNP were significantly higher in heart failure (447 [245-644] versus 87 [43-139] pg/mL). By multivariate logistic regression analysis, BNP (odds ratio of 44, [3.6-531], p=0.003) provided independent and incremental diagnostic information over the clinical score of Boston criteria (2.25, [1.3-3.9], p=0.0037). A BNP value of >142 pg/mL (area under the ROC curve of 0.89, p<0.0001) was 93 sensitive and 79% specific for the diagnosis of heart failure in this setting.. BNP is a reliable biomarker of new-onset heart failure with a preserved systolic function in hypertensive patients, in particular older, hospitalized for acute dyspnea and can be safely integrated in the diagnostic strategy.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cardiac Output, Low; Dyspnea; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Systole; Ventricular Function, Left

We studied the efficacy of valsartan (Val) to slow cardiovascular disease progression in asymptomatic high-risk prehypertensive or hypertensive patients with blood pressure (BP) controlled to <140/90 mm Hg and with evidence for functional or structural alterations in the cardiovascular system.. Identifying individuals with early markers for cardiovascular disease raises the possibility for pharmacotherapy to slow progression and delay or prevent future morbid events.. Seventy-six subjects with a Rasmussen Disease Score (RDS) of 6 or higher were randomized double-blind to receive placebo (Plac) or Val 160 mg once daily for 6 months followed by 6 months of single-blind Val in both groups. A panel of 10 tests, including large and small artery elasticity, resting and treadmill exercise BP, carotid intimal-media thickness, retinal vascular photography, micro-albuminuria, electrocardiography, echocardiography, and plasma B-type natriuretic peptide, was performed at baseline and after 6 and 12 months of treatment. Each test result was scored as normal (0), borderline (1), or abnormal (2), and the total RDS was calculated by adding all the scores of the individual tests.. Valsartan significantly reduced the RDS after 6 months versus Plac (p < 0.03) and at 12 months (either 12 or 6 months of Val, p < 0.0001). The major contribution in risk score reduction was due to an increase in small artery elasticity and a decrease in BP, and after 12 months there was a reduction in left ventricular mass index (p < 0.03).. Valsartan can slow progression and/or reverse early cardiovascular disease in asymptomatic high-risk patients with prehypertension or BP controlled to <140/90 mm Hg.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Cardiovascular Diseases; Comorbidity; Coronary Artery Disease; Disease Progression; Double-Blind Method; Exercise Test; Female; Fluorescein Angiography; Health Status Indicators; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Tetrazoles; Valine; Valsartan

We examined the relationship between plasma B-type natriuretic peptide (BNP) level and diurnal variability pattern of blood pressure (BP). Twenty-four-hour ambulatory BP monitoring was performed in 98 patients with asymptomatic essential hypertension, and the patients were classified into four groups according to their circadian BP variation profiles: dippers (n=29), nondippers (n=36), extreme dippers (n=19), and risers (n=14). Plasma BNP was measured by enzyme immunoassay. Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Significant differences in plasma BNP levels among the types of circadian BP variations were demonstrated by analysis of variance (p<0.0005). Nondippers and risers showed significantly higher plasma BNP levels (mean [range: -1 SD and +1 SD]: 16.1 [6.3, 41.6] pg/mL and 29.2 [15.9, 53.4] pg/mL, respectively) than dippers (8.4 [3.7, 19.1] pg/mL). The area under the receiver operating characteristics curve for distinguishing patients with abnormal circadian BP variation from those with normal variation was 0.72, indicating that plasma BNP levels were useful for distinguishing between these patients. Specificity of 69% and sensitivity of 72% were obtained with a cut-off value of 10.5 pg/mL (log plasma BNP, 1.02) for distinguishing the abnormal diurnal BP profile group from the normal group. In conclusion, hypertensive patients with abnormal diurnal BP variation patterns (nondippers, extreme dippers, and risers) showed higher plasma BNP levels than those with normal circadian BP variation (dippers). Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability, which increases the risk of cardiovascular events.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Electrocardiography; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity

Inappropriate left ventricular mass is present when the value of left ventricular mass exceeds individual needs to compensate hemodynamic load imposed by increased blood pressure. The goal of this study was to investigate whether plasma concentration of cardiotrophin-1, a cytokine that induces exaggerated hypertrophy in cardiomyocytes with hypertensive phenotype, is related to inappropriate left ventricular mass in patients with essential hypertension. The study was performed in 118 patients with never-treated hypertension and without prevalent cardiac disease. The left ventricular mass prediction from stroke work (systolic blood pressurexDoppler stroke volume), sex, and height (in meters(2.7)) was derived. An observed left ventricular mass/predicted left ventricular mass value >128% defined inappropriate left ventricular mass. Plasma cardiotrophin-1 was measured by an enzyme-linked immunosorbent assay. The studies were repeated in a group of 45 patients after 1 year of antihypertensive treatment. At baseline 67 and 51 patients presented with appropriate and inappropriate left ventricular mass, respectively. Plasma cardiotrophin-1 was higher (P<0.001) in patients with inappropriate mass than in patients with appropriate mass and normotensive controls. A direct correlation was found between cardiotrophin-1 and observed left ventricular mass/predicted left ventricular mass ratio (r=0.330, P<0.001) in all hypertensive patients. After treatment, plasma cardiotrophin-1 decreased and increased in patients in which inappropriate left ventricular mass regressed and persisted, respectively, despite a similar reduction of blood pressure in the 2 subgroups of patients. Albeit descriptive in nature, these results suggest the hypothesis that an excess of cardiotrophin-1 may contribute to inappropriate left ventricular growth in hypertensive patients.

Topics: Adult; Aged; Angiotensin II Type 2 Receptor Blockers; Antihypertensive Agents; Atenolol; Biomarkers; Blood Pressure; Cytokines; Diastole; Female; Heart Ventricles; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Systole; Ultrasonography

To prevent cardiovascular disease, targeting aldosterone synthesis and release may be clinically important. Aldosterone production in the adrenal gland is mediated mainly by the T-type calcium channel in vitro. Efonidipine inhibits both L- and T-type Ca channels. To compare the effects of efonidipine on neurohumoral factors with those of amlodipine, an L-type Ca channel blocker, we studied 40 essential hypertensive outpatients. Forty patients who had been administered amlodipine for more than 1 year were treated with efonidipine for 6 months in place of amlodipine. Substituting efonidipine for amlodipine had no significant effect on clinic systolic blood pressure or the plasma levels of brain natriuretic peptide, norepinephrine or active renin. However, the heart rate was significantly decreased (72.0+/-1.3 vs. 69.8+/-1.3 beats/min, p<0.01) and the plasma aldosterone level was also significantly decreased after efonidipine treatment (97.7+/-7.9 vs. 79.7+/-5.6 pg/mL, p<0.0001). Changes in the aldosterone level correlated with the baseline value before the replacement of amlodipine by efonidipine (r=-0.769, p<0.0001). These findings indicate that at the effective antihypertensive doses of efonidipine and amlodipine, efonidipine significantly decreases heart rate and plasma aldosterone level compared with those under amlodipine treatment in hypertensive patients.

Topics: Aged; Aged, 80 and over; Aldosterone; Amlodipine; Blood Pressure; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrophenols; Norepinephrine; Organophosphorus Compounds

Increased blood pressure (BP), night: day BP ratio, and heart rate is seen in Turner syndrome (TS), and an increased risk of ischaemic heart disease and type 2 diabetes, as well as aortic dilatation and dissection. We hypothesized that altered heart rate variability is present in TS in comparison with controls, and can be influenced by hormonal replacement therapy (HRT).. We examined the impact of HRT on sympathovagal control of heart rate variability. Patients (n = 8, aged 29.5 +/- 5.3 years; no treatment or HRT) and controls (n = 8, aged 28.5 +/- 4.2 years; no treatment) were examined by short-term spectral analysis (supine-standing), bedside neuropathy tests, and 24-h ambulatory BP. N-terminal pro-brain natriuretic peptide (BNP), renin, aldosterone and urinary albumin excretion was determined. The interaction between position and status (TS or control) was examined for data from spectral analysis.. Low-frequency (LF) power, coefficient of component variation of LF (both measures of sympathetic and vagal activity), and the LF: high-frequency (HF) power ratio (a measure of sympathovagal balance) were diminished in TS compared with controls, especially during standing. Systolic and diastolic night ambulatory BP (both P = 0.03), and systolic and diastolic night: day ratio (P = 0.01; P = 0.004) was increased in TS. During HRT diastolic day (P = 0.05) and 24-h diastolic ambulatory BP (P = 0.08) decreased. N-terminal pro-BNP was elevated in TS.. Decreased sympathovagal balance or tone and nocturnal hypertension is present in TS, and N-terminal pro-BNP is elevated. HRT did not modulate the sympathovagal tone, but decreased BP. These changes may be linked to the increased cardiovascular risk and possibly the increased risk of aortic dilatation in TS.

Topics: Adult; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cross-Over Studies; Female; Heart Rate; Hormone Replacement Therapy; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Posture; Sympathetic Nervous System; Turner Syndrome; Vagus Nerve

The aim of this study was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) on B-type natriuretic peptide (BNP) and to determine the effect of nasal continuous positive airway pressure (nCPAP) treatment on BNP levels.. Increased sympathetic activity, repetitive rises in blood pressure, and apnea-induced wall stress may contribute as a trigger to release BNP in OSAS. However, there is uncertainty about whether OSAS affects BNP and whether application of nasal continuous positive airway pressure (nCPAP) ventilation affects release of BNP.. A prospective study in 69 consecutive patients with suspected sleep disordered breathing referred to our sleep laboratory was conducted. OSAS was confirmed in 26 normotensive and 34 hypertensive patients and ruled out in nine normotensive patients (controls) by polysomnography (PSG).. Baseline N-terminal fragment of BNP prohormone (NT-pro-BNP) did not differ significantly between OSAS patients (hypertensive: mean +/-SEM 60.8+/-9.9 pg/ml, normotensive: 43.2+/-6.8 pg/ml) and controls (36.5+/-8.5 pg/ml). Application of CPAP resulted in a significant decrease of NT-pro-BNP in hypertensive (60.8+/-9.9 pg/ml to 47.6+/-7.4 pg/ml, p=0.023) and normotensive OSAS (43.2+/-6.8 pg/ml to 29.6+/-5.3 pg/ml, p=0.0002). In contrast, controls showed no significant differences in NT-pro-BNP after a second PSG (36.5+/-8.5 pg/ml to 40.7+/-12.3 pg/ml, p=0.597).. Normotensive and hypertensive OSAS was not associated with a significant elevation of NT-pro-BNP. Application of nCPAP decreased NT-pro-BNP levels significantly in normotensive and, in particular, hypertensive OSAS. These findings may provide further evidence of the potential for nCPAP to improve cardiovascular comorbidity and co-mortality in OSAS and sleep disordered breathing, in general.

Topics: Continuous Positive Airway Pressure; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sleep Apnea, Obstructive; Treatment Outcome

In this study we evaluated the effect of a dual blockade with enalapril and losartan on the reduction of overt macroproteinuria and its potential mechanism(s) in hypertensive patients with type 2 diabetes. Twenty-six hypertensive patients with type 2 diabetes at the baseline were administered 5 mg of enalapril once daily for 12 weeks. At the beginning of the study, the subjects were assigned to receive an add-on of 50 mg of losartan once daily or 5 mg of enalapril once daily for another 12 weeks. Blood samples were collected at the baseline, at the beginning, and at the end of the study for the measurement of laboratory parameters, and these data, including blood pressure, were compared between the two groups. Treatment with 5 mg of enalapril significantly decreased the systolic blood pressure level in both groups, and the addition of losartan and/or enalapril further decreased the levels. There was no difference in blood pressure between the two groups. However, the addition of losartan, but not enalapril, significantly decreased the urinary protein excretion level, plasma aldosterone, and hypersensitive-C-reactive protein at the end of the study. The results established that the dual blockade of angiotensin II with enalapril and losartan has a greater clinical benefit for high-risk patients with hypertension and advanced diabetic nephropathy.

Topics: Aged; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; C-Reactive Protein; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enalapril; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Proteinuria; Transforming Growth Factor beta

Angiotensin II receptor blockers (ARB) are now commonly used to treat hypertension because of their beneficial effects on cardiovascular remodeling. However, ARB treatment can not inhibit the left ventricular (LV) remodeling sufficiently, which may be related with aldosterone secretion. To inhibit the action of aldosterone during ARB treatment, the additional effects of an aldosterone blocker and spironolactone (SPRL) on LV hypertrophy in patients with essential hypertension was studied.. The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group). Seventy patients who underwent echocardiography every 6 months were analyzed and were also classified into 4 subgroups of LV geometric pattern according to the LV mass index (LVMI) and the relative wall thickness (RWT). The ARB treatment and the addition of SPRL significantly reduced the blood pressure, however, both treatments did not affect the LV geometry in both groups. The ARB treatment in the subgroups of concentric LV remodeling (RWT>or=0.45 and LVMI<125) and concentric LV hypertrophy (RWT>or=0.45 and LVMI>or=125) significantly reduced RWT. However, ARB treatment in all subgroups did not affect LVMI. The addition of SPRL only in the concentric LV hypertrophy subgroup significantly reduced the LVMI, despite similar changes in blood pressure.. These results indicated that the addition of SPRL treatment during the ARB treatment and conventional treatments is clinically useful to reduce the LVMI in hypertensive patients with concentric LV hypertrophy; however, does not improve the eccentric LV hypertrophy.

Topics: Aged; Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Echocardiography; Female; Heart Ventricles; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Spironolactone; Tetrazoles; Ventricular Remodeling

N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension.. In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint.. HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P < 0.01, and 11.5 versus 5.4%, P < 0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P < 0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P < 0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P < 0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P < 0.001).. Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.

Topics: Aged; Aged, 80 and over; Albumins; Antihypertensive Agents; Atenolol; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Confounding Factors, Epidemiologic; Creatinine; Endpoint Determination; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; ROC Curve; Scandinavian and Nordic Countries

To investigate the value of B-type natriuretic peptide (BNP) in diagnosing left ventricular diastolic dysfunction in patients with hypertension.. The left ventricular diastolic function and plasma BNP levels were assessed prospectively in 135 hypertensive patients.. The plasma BNP in patients with (n=61) and without (n=74) diastolic dysfunction was 122+/-105 and 18+/-16 pg/ml, respectively (p<0.001). Increased BNP levels were associated with systolic blood pressure (p<0.05), left ventricular mass index (p<0.001), the E/A ratio of transmitral flow (p<0.01) and the isovolumic relaxation time (p<0.01). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis of diastolic dysfunction revealed an area under the curve (accuracy) of 0.904 (p<0.01). Using a cut-off value of >40 pg/ml, the sensitivity and specificity of plasma BNP in diagnosing left ventricular diastolic dysfunction were 79% and 92%, respectively.. The plasma BNP levels in patients with hypertension are closely related to left ventricular hypertrophy and filling impairment. Plasma BNP may be used to facilitate the diagnosis of left ventricular diastolic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP).. In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens.. There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate.. Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.

Topics: Aged; Atenolol; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments

To compare the effects of combined therapy of an angiotensin II receptor blocker (ARB; valsartan) and an angiotensin converting enzyme inhibitor (ACEI; perindopril) on blood pressure (BP), metabolic profiles, plasma brain natriuretic peptide (BNP) levels, echocardiographic findings, and aortic pulse wave velocity (PWV) with those of respective monotherapy in never-treated patients with essential hypertension.. This was a prospective randomized trial, in which there were 31 patients with essential hypertension and left ventricular hypertrophy (LVH) who visited the outpatient clinic of Oita Red Cross Hospital (14 women and 17 men; mean+/-SD age, 59+/-5 years). Each patient was randomly assigned to receive valsartan (160 mg/day, V group, n=10), perindopril (8 mg/day, P group, n=11), or a combination of valsartan (80 mg/day) and perindopril (4 mg/day, V+P group, n=10) for 40 weeks. Ambulatory BP monitoring (ABPM), echocardiographic findings, metabolic findings, plasma BNP levels, and brachial-ankle PWV (baPWV) were evaluated before and after the 40-week therapy.. The baseline and post-therapeutic BP levels were similar among the three groups. At baseline ABPM, non-dipping was observed in 80, 82, and 80% in the V, P, and V+P groups, respectively. Each 40-week therapy regimen comparably reduced ABP. The plasma BNP levels (P<0.0001 for each), left ventricular mass index (LVMI) (P<0.01 for each), and PWV values (P<0.0001 for each) were also reduced. However, when compared with either V or P group, the percentage reduction in LVMI (P<0.05 and P<0.005, respectively), BNP (P<0.05 for each), and baPWV values (P<0.005 and P<0.001, respectively) was greater in the V+P group.. Our findings suggest that, when compared with each monotherapy, perindopril and valsartan combination therapy exerts greater beneficial effects regarding the regression of LVH, reduction in BNP, and improvement of PWV in a selected group of essential hypertensive patients with LVH and high prevalence of non-dipping patterns.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Ankle; Aorta; Blood Pressure Monitoring, Ambulatory; Drug Therapy, Combination; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Perindopril; Prospective Studies; Pulse; Tetrazoles; Valine; Valsartan

Diastolic dysfunction is common in the elderly. Increased myocardial fibrosis, a major determinant of diastolic function, has been observed with advancing age. Spironolactone prevents age-related increases in myocardial fibrosis in old normotensive rats.. Spironolactone, via its antifibrotic activity, can improve diastolic function in the elderly with isolated diastolic dysfunction.. The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to 25 mg/day of spironolactone or placebo for 4 months. Mitral E/A and deceleration time, plasma levels of carboxy-terminal of procollagen type I (PICP), and brain natriuretic peptide (BNP) were measured at baseline and at the end of 4 months. Plasma level of potassium was also monitored to prevent clinically significant hyperkalemia.. There was no serious adverse event or clinically significant hyperkalemia in the spironolactone group. Compared with baseline values, spironolactone significantly improved mitral E/A ratio (0.71 +/- 0.08 vs. 0.84 +/- 0.19, p = 0.025) and deceleration time (285.5 +/- 73.1 vs. 230.0 +/- 54.7, p = 0.035). There were no significant differences in the magnitude of change in the levels of PICP and BNP between the two treatment groups.. Spironolactone may improve diastolic function in the elderly.

Topics: Aged; Aged, 80 and over; Blood Pressure; Coronary Artery Disease; Diastole; Double-Blind Method; Female; Fibrosis; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prospective Studies; Spironolactone; Time Factors; Treatment Outcome

A young patient presented with a cardiomegaly of unknown origin. The cardiologic examination revealed a severe eccentric left ventricular hypertrophy and a dilatation of the other heart cavities as well as a strongly impaired global systolic function. The patient was treated with an ACE inhibitor, a diuretic and with a beta-blocking agent. The dosages of which were adapted accordingly to the plasma concentration of N-terminal-pro-brain-natriuretic peptide (NT-proBNP). After five months of treatment, a decrease of the NT-proBNP level to nearly normal values along with a significant reduction of the heart dimensions and a substantial improvement of left ventricular function were found.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Diuretics; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Exercise Test; Heart Failure; Humans; Hypertension; Indapamide; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Perindopril; Propanolamines; Reference Values

N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure. We compared NT-proBNP levels in patients with and without a diagnosis of arterial hypertension.. Participants were recruited from a random sample of 999 inhabitants from the Community of Valencia (eastern Spain). Of these patients, 432 said they suffered from dyspnea and were referred to their hospital (10 hospitals involved), where blood samples were taken, an echo-Doppler study was performed, and the patients completed a questionnaire. Of the 432 participants with dyspnea, 215 gave informed consent for their inclusion in the study, and 202 completed the study. Hypertension was diagnosed in 72 participants and 130 were normotensive.. For the whole population, NT-proBNP, expressed as the median and range, was 88 (0-2586) pg/mL. When we compared hypertensive with normotensive participants, we found higher NT-proBNP levels in the former group: median 123, range 0-2184 pg/mL, versus median 77, range 0-2586 pg/mL (P<.01). When we excluded subjects with systolic left ventricular dysfunction, we found higher levels in participants with hypertension: 119 (0-2184 pg/mL) vs 72 (0-997 pg/mL) (P<.01). When we also excluded subjects with diastolic dysfunction, we found (median 85, range 0-430 pg/mL) and (median 66, range 0-997 pg/mL), respectively (p = NS).. In a population study of subjects with dyspnea, hypertensive patients have higher NT-proBNP levels than subjects with normal blood pressure. This difference disappeared when patients with diastolic dysfunction were excluded from the analysis. Hypertension can thus be a confounding factor that potentially decreases the specificity of NT-proBNP levels for the diagnosis of heart failure. These findings should be taken into account when conducting clinical and epidemiological studies in which patients with both heart failure and hypertension are included.

Topics: Aged; Echocardiography, Doppler; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Surveys and Questionnaires

N-terminal pro-brain natriuretic peptide (Nt-proBNP) and N-terminal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general population. We investigated whether high Nt-proBNP or Nt-proANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy.. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants in the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP and Nt-proANP were measured by immunoassay at baseline. The patients were followed for 60 +/- 5 months.. Using Cox regression analysis, the 25 CEP were predicted by ln(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) as well as ln(Nt-proANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the median value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular disease (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2%, NS). Nt-proANP showed the same tendency.. Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertension and LV hypertrophy, especially in patients without diabetes or clinically overt cardiovascular disease.

Topics: Aged; Anti-Infective Agents; Atenolol; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Stroke; Ultrasonography

This study compared the effects of amlodipine and valsartan on the sympathetic nervous system, the renin-angiotensin-aldosterone system, and brain natriuretic peptide, which are considered important parameters of the long-term prognosis. Seventy-three elderly patients, who had received antihypertensive treatment for more than 6 months with amlodipine, participated in this study. They were randomized to the V group (n = 36) and switched to valsartan from amlodipine, or to the A group (n = 37), which continued treatment with amlodipine. The dose of valsartan was set as that which controlled the blood pressure to the same extent as before switching. Blood samples were measured before and after 6 months of therapy. Data were analyzed by two-way analysis of variance with the Newman-Keuls test. In the V group, norepinephrine (from 597.0 +/- 52.9 to 475 +/- 43.8 pg/ml, p < 0.05) and aldosterone (from 74.5 +/- 7.0 to 53.9 +/- 5.3 pg/ml, p < 0.001) were decreased significantly after 6 months, although norepinephrine and aldosterone levels were unchanged in the A group. However, brain natriuretic peptide did not show a difference between the two groups. These findings suggested that valsartan is probably superior to amlodipine with respect to less activation of the sympathetic nervous system and preventing upregulation of the renin-angiotensin-aldosterone system.

Topics: Aged; Aldosterone; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Calcium Channel Blockers; Coronary Disease; Delayed-Action Preparations; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Receptor, Angiotensin, Type 1; Tetrazoles; Time Factors; Valine; Valsartan

Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infarction and stroke, and differences among the major drugs in their efficacy at preventing these individual endpoints. We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same. We studied 30 untreated hypertensive patients, aged 28-55 years, who were rotated through six 6-week periods of daily treatment with amlodipine 5 mg, doxazosin 4 mg, lisinopril 10 mg, bisoprolol 5 mg, bendrofluazide 2.5 mg or placebo. The best drug was repeated at the end of the rotation. Blood pressure readings and radial pulse tonometry (by Sphygmocor) were performed at each visit, and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide (BNP). The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave (T(R)) and the augmentation index (AI), which is the proportional increase in systolic pressure due to the reflected wave. There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis. Bisoprolol caused the greatest falls in blood pressure and T(R), but was the only drug to increase AI. This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels. There was a smaller elevation of BNP in women compared with men, as described previously, and this elevation also was associated with significantly higher values of AI. Other drugs reduced AI, and this was associated with a significant decrease in BNP by amlodipine. In conclusion, antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart, regarded as a sensitive measure of strain on cardiomyocytes. These differences may help to explain cause-specific differences in outcome in recent trials.

Topics: Adult; Analysis of Variance; Antihypertensive Agents; Aorta; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Determination; Cross-Over Studies; Double-Blind Method; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Pulsatile Flow; Radial Artery; Sex Factors

Hypertension guidelines recommend initial treatment with a beta-blocker or diuretic and adding the other drug where blood pressure is not controlled. We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient's response, and suggest a more rational approach to choosing best treatment.. Thirty-four young hypertensives (age 28-55, median 47) rotated in a double-blind, Latin-square, crossover fashion through 6 weeks of treatment each with amlodipine, doxazosin, lisinopril, bisoprolol, bendrofluazide and placebo. Blood pressure was measured at each visit. 'Best' drug, defined by efficacy and tolerability, was repeated at the end.. Rotation doubled the number of patients reaching target blood pressure (systolic < 140 mmHg) on one drug (P = 0.03). All five drugs were represented among the 'best' drugs. In six patients, the blood pressure on 'best' drug was at least 10 mmHg lower than on any other. Response to the 'best' drug was highly correlated (r = 0.79) with its previous administration. By contrast, there were only weak correlations between responses to pairs of drugs, except for angiotensin-converting enzyme (ACE) inhibitor (A) with beta-blocker (B), and calcium blocker (C) with diuretic (D) - each r = 0.71, P < 0.005). In these young patients, the majority of patients (23/34) responded best to a drug suppressing the renin system (A and B).. Patients vary reproducibly in their response to initial treatment, and switching among drugs can increase the efficacy of monotherapy. The results support an AB/CD scheme for choosing therapy, in which the first drug is taken from one of these pairs, and uncontrolled patients switch to one of the other pair.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bendroflumethiazide; Bisoprolol; Blood Pressure; Calcium Channel Blockers; Cross-Over Studies; Diuretics; Double-Blind Method; Doxazosin; Female; Heart Rate; Humans; Hypertension; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Renin-Angiotensin System; Sodium Chloride Symporter Inhibitors

We examined the effects of the vasodilator peptide adrenomedullin (AM) infused intravenously into subjects with essential hypertension. Eight men 39 to 58 years old with uncomplicated hypertension (147/96+/-5/3 mm Hg at baseline) were studied in a placebo-controlled, crossover design. Each subject received intravenous AM in a low and a high dose (2.9 and 5.8 pmol. kg(-1). min(-1) for 2 hours each) or vehicle-control (Hemaccel) infusion in a random order on day 4 of a controlled metabolic diet (80 mmol/d Na(+), 100 mmol/d K(+)). Plasma AM reached pathophysiological levels during infusion (18+/-4 pmol/L in low dose, 34+/-9 pmol/L in high dose) with a concurrent rise in plasma cAMP (+8.4+/-1.2 pmol/L, P:<0. 05 compared with control). Compared with control, high-dose AM increased peak heart rate (+17.8+/-2.3 bpm, P<0.01), lowered systolic (-24.6+/-0.9 mm Hg; P<0.01) and diastolic (-21.9+/-1.4 mm Hg; P<0.01) blood pressure, and increased cardiac output (+1.0+/-0. 1 L/min in low dose, +2.9+/-0.2 L/min in high dose; P<0.01 for both). Despite a rise in plasma renin activity during high dose (P<0.05), aldosterone levels did not alter. Plasma norepinephrine levels increased 1295+/-222 pmol/L (P<0.001) and epinephrine increased 74+/-15 pmol/L (P<0.05) with high-dose AM compared with control. AM had no significant effect on urine volume and sodium excretion. In subjects with essential hypertension, the intravenous infusion of AM to achieve pathophysiological levels produced significant falls in arterial pressure, increased heart rate and cardiac output, and stimulated the sympathetic system and renin release without concurrent increase in aldosterone. Urinary parameters were unaltered. Although AM has potent hemodynamic and neurohumoral effects in subjects with essential hypertension, the threshold for urinary actions is set higher.

Topics: Adrenomedullin; Adult; Aldosterone; Atrial Natriuretic Factor; Creatinine; Cross-Over Studies; Cyclic AMP; Dose-Response Relationship, Drug; Epinephrine; Hemodynamics; Humans; Hydrocortisone; Hypertension; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Peptides; Potassium; Potassium, Dietary; Prolactin; Renin; Sodium; Sodium, Dietary

Responses of endocrine systems to acute and chronic salt loading were examined in normotensive and hypertensive subjects. In the acute salt load study, isotonic saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects and 12 patients with essential hypertension. Plasma noradrenaline was suppressed by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic peptide concentration was significantly increased in the hypertensive patients (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the chronic salt load study, 9 normotensive subjects and 30 patients with essential hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the basis of the blood pressure change, 17 hypertensive patients were classified as salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients had suppressed plasma renin activity even during low-salt intake. During high salt intake, the plasma noradrenaline concentration failed to decrease in the salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive patients (-33%, p < 0.01). The high-salt intake also increased plasma concentrations of brain natriuretic peptide as well as atrial natriuretic peptide in all groups. In the salt-sensitive hypertensive patients, there was a positive correlation between the increase in blood pressure and that in atrial natriuretic peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is involved in chronic changes in body fluid volume. In patients with essential hypertension, acute volume expansion also evokes the response of brain natriuretic peptide. Salt-sensitive hypertension seems to be characterized by blunted response of the sympathetic nervous system. In addition, an increase in atrial natriuretic peptide is likely to play an important role in mechanisms counteracting salt-induced elevation of blood pressure.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Sodium Chloride; Sodium, Dietary; Water-Electrolyte Balance

Plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) are high in patients with hypertension and congestive heart failure. The present study examined changes in plasma ANP and BNP concentrations during 1 year of monotherapy with enalapril in elderly hypertensive patients with left ventricular (LV) hypertrophy. Eight elderly hypertensive patients with LV hypertrophy were treated with enalapril for 1 year, during which time serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of ANP and BNP. Enalapril maintained systolic and diastolic blood pressure in the normal range for over 1 year. Treatment significantly reduced posterior wall thickness at 6 months, and more so at 1 year, and tended to reduce septal wall thickness and LV mass index at 1 year. LV ejection fraction was slightly but significantly increased at 1 year. Plasma ANP and BNP, which were markedly elevated at study entry, both decreased after 1 year of enalapril. These results suggest that 1 year of treatment with enalapril caused both a modest regression of LV hypertrophy and a modest improvement in LV systolic function in our selected group of elderly hypertensive patients. The drug reduced elevated plasma ANP and BNP levels but did not alter BUN and serum creatinine levels. Enalapril appears to be useful for the treatment of elderly hypertensive patients with LV hypertrophy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Electrocardiography; Enalapril; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin; Systole; Ventricular Function, Left

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater increments in hypertensive patients than in normotensives. Plasma concentrations of BNP increased only in patients with hypertension and the levels of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography. In contrast, plasma adrenomedullin did not change with exercise in either group. These results suggest that secretion patterns of these peptides are regulated by different mechanisms and that the amount and kind of peptides mobilized by exercise may depend on the underlying diseases or pathophysiologic condition.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Exercise; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Reference Values

Plasma concentrations of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in severe hypertension, acute myocardial infarction, and heart failure. In the current study of individuals with essential hypertension, we have documented the hemodynamic, hormonal, and endocrine effects of infusions of these two peptides given alone or in combination in equimolar doses calculated to induce increments in plasma peptides to concentrations (30 to 60 pmol/L) observed in these disease states. The metabolic clearance rate of ANP (4.56 +/- 0.62 L/min) was greater than that for BNP (3.4 +/- 0.23 L/min, P <.001). Infusions of each cardiac hormone impaired the clearance of coinfused peptide. All peptide infusions enhanced natriuresis (17% to 70% above preinfusion levels versus placebo, 6%; P <.001), lowered blood pressure (10 to 18 mm Hg fall in mean arterial pressure below placebo levels; P <.001), increased hematocrit, suppressed the renin-angiotensin-aldosterone system, and enhanced plasma norepinephrine concentrations. The natriuretic and blood pressure-lowering effects of BNP were twofold to threefold those of ANP. In contrast, ANP-induced increments in plasma and urinary second messenger (cGMP) levels were greater than those for BNP. Both peptides suppressed the renin-angiotensin-aldosterone system (approximately one-third fall in renin activity and plasma aldosterone) and enhanced plasma norepinephrine concentrations (+30%) to a similar degree. Increments in plasma ANP and BNP that occur simultaneously in cardiovascular disease states appear capable of causing hemodynamic, endocrine, and renal effects that would tend to ameliorate conditions such as hypertension or heart failure.

Topics: Atrial Natriuretic Factor; Hemodynamics; Hormones; Humans; Hypertension; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Many factors have been reported to stimulate the release of brain natriuretic peptide (BNP) as well as atrial natriuretic peptide (ANP). In hypertensive patients, however, little is known about whether these factors differ from those in normotensive subjects or if they are influenced by antihypertensive treatment. We measured the plasma concentrations of BNP and ANP in 12 hypertensive patients and examined the chronic effects of beta-adrenoceptor blockade on BNP secretion during exercise with a bicycle ergometer. The exercise raised both plasma BNP and ANP with concomitant increases in systolic blood pressure, heart rate (HR) and plasma norepinephrine (NE) and epinephrine (Epi) before and after treatment. Before treatment, the changes in ANP and BNP correlated with that in HR (p < 0.05). After treatment 4 wk of treatment, the change in ANP correlated with those in NE and Epi as well as HR. Multivariate regression analysis indicated that only NE was a significant stimulus for ANP secretion during the treatment period. As for BNP, HR was the only significant stimulant for its secretion both before and after treatment. In essential hypertension, beta-adrenergic receptor blockade affected the factors stimulating exercise-induced ANP release but not those stimulating BNP release. BNP release, therefore, seems to be stimulated by similar but distinct factors from those that stimulate ANP release.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Atrial Natriuretic Factor; Bisoprolol; Blood Pressure; Body Mass Index; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Physical Exertion; Regression Analysis

We assessed the cardiovascular and renal effects of human brain natriuretic peptide (BNP) infused at a dose inducing an increase in plasma BNP to pathophysiologic levels, in eight hypertensive patients in a randomized, placebo-controlled, cross-over study. Left ventricular performance, cardiac output (echocardiography), heart rate, arterial pressure, glomerular filtration rate (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling (lithium clearance method), and urine flow rate were measured in the infusion and postinfusion periods (1 h each), together with plasma BNP and the urinary excretion rate of cGMP. Plasma BNP levels increased from 2.90 +/- 0.74 to 36.43 +/- 5.51 pmol/L (P < .01) at the end of the infusion and were still elevated at the end of the postinfusion period (7.03 +/- 1.41 pmol/L, P < .05). The urinary excretion of cGMP was also significantly higher during BNP infusion. Left ventricular performance, cardiac output, arterial pressure, and peripheral vascular resistance were not affected by BNP. Peptide infusion induced a significant increase in GFR (placebo, 115 +/- 24; BNP, 147 +/- 19 mL/min), sodium excretion (placebo, 129 +/- 40; BNP, 243 +/- 60 mumol/min), and urine flow rate. All these effects were observed also in the postinfusion period. The natriuretic effect of BNP was attributable to both an increase in filtered sodium load and a reduction of distal sodium reabsorption. These results suggest that BNP may contribute to maintain renal function and sodium excretion in patients with essential hypertension.

Topics: Adult; Creatinine; Cross-Over Studies; Female; Heart Ventricles; Hemodynamics; Hormones; Humans; Hypertension; Infusions, Intravenous; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Single-Blind Method; Sodium

To determine the major stimuli for the release of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), we measured their plasma concentrations in 14 normal subjects and 19 patients with essential hypertension during exercise with a bicycle ergometer. The plasma levels of both hormones at baseline were significantly higher in the hypertensive group than in the controls (p < 0.05). The exercise raised both the plasma BNP and ANP, with concomitant increases in systolic blood pressure (SBP), heart rate (HR) and plasma norepinephrine (NE) or epinephrine (Epi) in each group. In the controls the change in ANP correlated with those in SBP, HR and NE (p < 0.05), and similarly the change in BNP with those in SBP, HR, NE and Epi (p < 0.05). In multivariate regression analysis only NE was found to be a significant stimulus for ANP secretion, whereas SBP or Epi was related to BNP release. In the hypertensives the change in ANP correlated with those in HR and NE, but on multivariate regression analysis the change in ANP correlated only with that in HR. The change in BNP in the hypertensives correlated only with that in HR. These findings indicate that in normal subjects the exercise-induced release of BNP and ANP is more sensitive to a similar but slightly different sympathetic stimulus, whereas in hypertensives the major stimulus for the release of both hormones is heart rate, indicating that the mediators for BNP or ANP release are altered by some factors involved in hypertension.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Exercise Test; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Regression Analysis

Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension.. Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP).. ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related.. Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Lisinopril; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Treatment Outcome

To examine the changes in plasma brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and blood pressure in patients with essential hypertension on a low, normal and high sodium intake.. Twelve patients with mild-to-moderate essential hypertension were studied. Plasma, urinary and blood pressure measurements were made with the patients on their usual sodium intake, then on the fifth day of a low (10 mmol/day) and on the fifth day of a high (350 mmol/day) sodium intake, the sequence being allocated randomly.. Plasma levels of BNP and ANP increased significantly on the high sodium intake compared with when the patients were on their normal diet. The mean blood pressure on the high sodium intake was not significantly different from that with the patients on their normal diet. In contrast, plasma BNP and ANP decreased on the low sodium intake, but were not significantly different compared with when the patients were on their normal diet. However, there was a significant reduction in the mean blood pressure on the low sodium intake compared with when the patients were on their normal diet. Compared with the normal diet, BNP and ANP plasma levels showed similar percentage decreases on the low sodium intake and similar percentage increases on the high sodium intake.. These findings suggest that BNP and ANP are released in response to a common stimulus during changes in dietary sodium intake. The changes in plasma BNP and ANP observed with sodium restriction and sodium loading indicate the potential importance of BNP and ANP as a dual peptide system contributing to the maintenance of sodium balance and blood pressure regulation in patients with essential hypertension, during changes in dietary sodium intake.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Diet, Sodium-Restricted; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Sodium

In contrast to the wealth of information available concerning the response of plasma atrial natriuretic peptide to changes in pressure and volume status and to inhibition of endopeptidase 24.11, very little is known of possible concomitant effects on brain natriuretic peptide. The effects of change in posture, pressor infusions of angiotensin II, or inhibition of endopeptidase 24.11 were documented in two groups of patients with essential hypertension receiving one of two orally active inhibitors (SCH 42495 or UK 79300) in double-blind, placebo-controlled, random-order crossover studies. Sustained (4 days) inhibition of endopeptidase 24.11 with either inhibitor significantly enhanced plasma atrial natriuretic peptide (P < .05, both groups) but suppressed plasma brain natriuretic peptide (P < .01, both groups) in association with significant falls in arterial pressure (P < .05, both groups). Assumption of the recumbent posture increased plasma atrial natriuretic peptide (20 +/- 5 vs 13 +/- 3 pmol/L, P < .05), whereas brain natriuretic peptide was unchanged (7 +/- 0.3 vs 7 +/- 0.4 pmol/L, NS). Pressor infusions of angiotensin II increased plasma levels of both atrial natriuretic peptide and brain natriuretic peptide (33 +/- 11 vs 17 +/- 4 pmol/L, P < .05, and 7.5 +/- 0.6 vs 5.5 +/- 0.4 pmol/L, P < .05, respectively). In contrast to atrial natriuretic peptide, brain natriuretic peptide probably is primarily regulated by left ventricular load rather than by atrial distending pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Double-Blind Method; Humans; Hypertension; Indans; Male; Methionine; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Nerve Tissue Proteins; Posture; Propionates; Time Factors

Documentation of the renal, hormonal and haemodynamic effects and plasma clearance of human brain natriuretic peptide (BNP) given (in a dose inducing increases in plasma BNP concentrations to pathophysiological levels) to patients with essential hypertension.. Six male patients with untreated, uncomplicated, mild-to-moderate essential hypertension underwent placebo-controlled single-blind studies in balanced random order. Human BNP (2 pmol/kg per min) and vehicle were given as constant intravenous infusions in a volume of 15 ml/h for 2 h. Continuous recording of intra-arterial blood pressure and heart rate, together with serial blood samples (for hormone assays) and 30-min urine collections, were obtained throughout the studies from 90 min before commencement of infusions to 90 min after completion of infusions.. Achieved intra-infusion plasma BNP immunoreactivity (20-30 pmol/l) was similar to levels previously observed in heart failure. Plasma cyclic GMP was increased. Sodium excretion rose to 2.5-fold placebo values. Plasma aldosterone fell to 50% of placebo values. Blood pressure and heart rate were unchanged. The metabolic clearance rate (5.0 +/- 0.4 l/min) and plasma half-life (19.5 min) indicated that BNP has a large volume of distribution (141 +/- 16 litre).. In essential hypertension pathophysiological plasma concentrations of human BNP have significant acute effects promoting natriuresis and suppressing plasma aldosterone. These effects are similar to those of ANP, but the plasma half-life and volume of distribution of BNP are considerably greater than those of atrial natriuretic peptide. These two hormones may play separate complementary roles in fluid volume and blood pressure homeostasis.

Topics: Aldosterone; Cyclic GMP; Half-Life; Homeostasis; Humans; Hypertension; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin

Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP.. hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models.. Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment.. Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

Topics: Biomarkers; Blood Pressure; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Troponin; Troponin T; Vasodilator Agents

The association between pulse rate (PR) and short-term PR variability and hypertensive organ damage has not been clarified. We enrolled 1439 patients from the J-HOP study. We calculated the standard deviation (SD) of PR in the nighttime using nighttime PR measurements at 30-min intervals. The SDs of PR (PR-SD) at nighttime were divided into quartiles (Q1-Q4). Nondipper PR was defined as (awake PR-sleep PR) < 0.1. Brain natriuretic peptide (BNP) levels were higher in patients with nondipper PR status in Q4 of PR-SD (nondipper PR/PR-SD Q4) than those with nondipper PR/PR-SD Q1-Q3 (37.8 vs 21.9 pg/mL, p = 0.041). The percentage of BNP > 100 pg/mL for patients with dipper PR/PR-SD Q1-Q3 was 5.2%, that for dipper PR/PR-SD Q4 was 4.8%, that for nondipper PR/PR-SD Q1-Q3 was 13.0%, and that for nondipper PR/PR-SD Q4 was 20.0% (ANOVA p < 0.001). In conclusion, BNP was high in patients having nondipper PR and high nocturnal PR-SD. Conceptual figure of subclinical heart failure and nondipper PR, PR variability. PR: pulse rate.

Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Heart Rate; Humans; Hypertension; Natriuretic Peptide, Brain; Sleep

Topics: Blood Pressure; Cardiovascular Diseases; Heart Disease Risk Factors; Heart Rate; Humans; Hypertension; Natriuretic Peptide, Brain; Risk Factors

This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients.. A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis.. Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively.. Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

Topics: Aged; Biomarkers; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Prognosis; Stroke Volume

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity.

Topics: Aortic Valve; Aortic Valve Stenosis; Fibroblasts; Gallium Radioisotopes; Humans; Hypertension; Molecular Imaging; Natriuretic Peptide, Brain; Pilot Projects; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

To investigate the correlation between NPPB gene variants and pulse pressure hypertension and the underlying regulatory mechanisms and try to confirm that NPPB may be a potential molecular target of gene therapy for pulse pressure hypertension. A total of 898 participants were recruited from the First Affiliated Hospital of Fujian Medical University and the plasmids with differential expression of NPPB were constructed. Genotype distribution of NPPB(rs3753581, rs198388, and rs198389)was analyzed and the expression of N-terminal pro-B-type natriuretic peptide(NT-proBNP) and renin-angiotensin -aldosterone system(RAAS) related indicators were identified in the groups studied. According to a genotype analysis, there was a significant difference in the genotype distribution of NPPB rs3753581 among the groups (P = 0.034). In logistic regression analysis, NPPB rs3753581 TT was associated with a 1.8-fold greater risk of pulse pressure hypertension than NPPB rs3753581 GG (odds ratio = 1.801; 95% confidence interval: 1.070-3.032; P = 0.027). The expression of NT-proBNP and RAAS related indicators in clinical and laboratory samples showed striking differences. The activity of firefly and Renilla luciferase in pGL-3-NPPB-luc (-1299G) was higher than pGL-3-NPPBmut-luc(-1299 T)(P < 0.05). The binding of NPPB gene promoter rs3753581 (-1299G) with transcription factors IRF1, PRDM1, and ZNF263 was predicted and validated by the bioinformatics software TESS and chromatin immunoprecipitation(P < 0.05). NPPB rs3753581 was correlated with genetic susceptibility to pulse pressure hypertension and the transcription factors IRF1, PRDM1, and ZNF263 may be involved in the regulation of NPPB rs3753581 promoter (-1299G) on the expression of NT-proBNP/RAAS.

Topics: Blood Pressure; DNA-Binding Proteins; Genotype; Humans; Hypertension; Interferon Regulatory Factor-1; Natriuretic Peptide, Brain; Peptide Fragments; Positive Regulatory Domain I-Binding Factor 1; Transcription Factors

The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population.. We measured NT-proBNP in stored blood samples collected from participants 1 year or older who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults 20 years or older without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories.. Among US adults without CVD, the prevalence of elevated NT-proBNP (≥125 pg/ml) was 27.2% among those with untreated hypertension, 24.9% among those with treated controlled hypertension, and 43.3% among those with treated uncontrolled hypertension. Over a median follow-up of 17.3 years and after adjusting for demographic and clinical risk factors, US adults with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and cardiovascular mortality (HR 3.83, 95% CI 2.34, 6.29), compared to adults without hypertension and with low levels of NT-proBNP (<125 pg/ml). Across all levels of SBP and irrespective of antihypertensive medication use, elevated NT-proBNP was associated with an increased risk of mortality, compared to low levels of NT-proBNP.. Among a general population of adults free of CVD, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.

Topics: Adult; Biomarkers; Blood Pressure; Cardiovascular Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; Nutrition Surveys; Peptide Fragments; Prevalence; Prognosis

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiomyopathies; Fibrosis; Heart Atria; Humans; Hypertension; Natriuretic Peptide, Brain; Serine Endopeptidases; Siblings

Hypertensive pulmonary edema is a fatal condition unless early and properly diagnosed and managed. Central blood pressure (cBP) has been proven to be more associated with adverse cardiovascular events. We aimed to study the correlation between cBP and heart damage in patients with Hypertensive pulmonary edema.. We included 50 patients admitted to the emergency department in a university hospital for hypertensive pulmonary edema, 27 women and 23 men aged 50 to 70 years. We excluded patients with suspected acute coronary syndrome, significant valvular heart disease, and pericardial diseases. We measured cBP non-invasively from pulse wave analysis of the brachial artery. Brain natriuretic peptide (BNP) and cBP were repeatedly measured for every patient.. The median BNP levels of patients significantly decreased from 284 pg/ml (232-352.5) to 31.5 pg/ml (24-54) on discharge, P < 0.001. We found a significant correlation between admission BNP and central SBP (cSBP), urea, creatinine, arterial blood gases parameters, and left ventricular end-diastolic diameter (LVEDD). Concurrently, BNP at discharge was correlated with age, central DBP (cDBP), urea, creatinine, LVEDD, partial oxygen pressure (pO2), and oxygen saturation (SO2). Delta BNP was correlated with cSBP, peripheral SBP, urea, creatinine, pO2, and SO2. Linear regression analysis revealed that creatinine, and cSBP, were independent predictors of admission BNP, while urea and cDBP were the independent predictors of discharge BNP.. This simple, noninvasive method of cBP measurement was significantly associated with the extent of myocardial damage in patients presenting with hypertensive pulmonary edema.

Topics: Aged; Blood Pressure; Blood Pressure Determination; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema

Heart failure (HF) is frequent in patients with diabetes mellitus (DM), and early detection improves prognosis. We investigated whether analysis of brachial blood pressure (BP) in daily practice can identify patients with DM and high risk for subsequent HF, as defined by brain natriuretic peptide (BNP) >50 pg/ml.. 3,367 outpatients with DM without a history of cardiovascular disease were enrolled in a prospective study.. Age (mean ± SD) was 56 ± 14 years, 57% were male, 78% had type 2 DM, and HbA1C was 7.4 ± 1.4%. A history of hypertension was recorded in 43% of patients and uncontrolled BP was observed in 13%. BNP concentration (mean ± SD) was 21 ± 21 ng/l and 9% of patients had high risk of incident HF. Brachial pulse pressure (PP) was the best BP parameter associated with high risk of incident HF compared with diastolic, systolic, or mean BP (area under the receiver operating characteristic curve: 0.70, 0.65, 0.57, and 0.57, respectively). A multivariate analysis demonstrated that elevated PP was independently associated with high risk of incident HF (odds ratio [95% confidence interval, CI]: 2.1 [1.5-2.8] for PP ≥65 mm Hg). Study of central aortic BP and pulse wave velocity on 117 patients demonstrated that high risk of incident HF was associated with increased arterial stiffness and subendocardial ischemia. After a mean follow-up of 811 days, elevated PP was associated with increased all-cause mortality (hazard ratio [95% CI]: 1.7 [1.1-2.8]).. Brachial PP is powerful and independent "easy to record" BP parameter associated with high risk of incident HF in diabetic patients.

Topics: Adult; Aged; Blood Pressure; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulse Wave Analysis

Excessive salt intake causes hypertension and heart diseases. B-type natriuretic peptide (BNP) is a surrogate marker of heart disease, and a slightly elevated BNP level is associated with a poor prognosis. Our previous cross-sectional study demonstrated that plasma BNP has a significant positive association with daily salt intake in the general population. However, the relationship between changes in salt intake and changes in plasma BNP remains unknown. We recruited 3051 participants without hypertension or electrocardiogram abnormalities who underwent annual health check-ups for two consecutive years. Clinical parameters, including plasma BNP, were obtained, and daily salt intake was evaluated using urinary samples. Annual changes in these parameters were calculated. The median plasma BNP level was 12.9 pg/mL, and the daily salt intake was 8.73 ± 1.89 g. The annual changes in plasma BNP and daily salt intake were 4.79 ± 36.38% and 2.01 ± 21.80%, respectively. Participants in the highest quartile of annual changes in daily salt intake showed the largest annual changes in plasma BNP. Annual changes in plasma BNP indicated a significant positive association with daily salt intake. Moreover, multiple linear regression analyses revealed that annual changes in plasma BNP showed a significant positive association with daily salt intake after adjustments. Our study showed a significant positive relationship between annual changes in plasma BNP and annual changes in daily salt intake. The suppression of plasma BNP is therefore induced by salt intake restriction. The monitoring of plasma BNP while reducing salt intake may therefore prevent heart diseases and lead to improved prognoses in the general population without heart diseases.

Topics: Heart Diseases; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Sodium Chloride, Dietary

Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF.. This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected.. A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001).. Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.

Topics: Adult; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Creatinine; Drug Combinations; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Retrospective Studies; Tetrazoles; Uric Acid; Valsartan

We aim to assess the association of cardiovascular medications with outcomes of patients referred to the diagnostic heart failure (HF) clinic with symptoms or signs of possible HF, raised N-terminal pro-brain-type natriuretic peptide (NT-proBNP) but no evidence of HF on transthoracic echocardiography (TTE).. Data were collected prospectively into the Sheffield HEArt Failure (SHEAF) registry between April 2012 and January 2020. The inclusion criteria were symptoms or signs suggestive of HF, NT-proBNP >400 pg/mL, but no evidence of HF on TTE. Cox proportional-hazards regression model was used to investigate the association between the survival time of patients and different cardiovascular medications. The outcome was defined as all-cause mortality.. From the SHEAF registry, we identified 1766 patients with raised NT-proBNP with no evidence of HF on TTE. Survival was higher among the younger patients, and among those with hypertension or atrial fibrillation (AF). Mortality was increased with male gender, valvular heart disease and chronic kidney disease. Using univariate Cox proportional-hazards regression, the only cardiac therapeutic agent independently associated with all-cause mortality was beta-blocker (HR 0.86; 95% CI: 0.77 to 0.97; p=0.02). The use of beta-blockers was significantly higher in patients with AF (63% vs 39%, p<0.01) and hypertension (51% vs 42%, p<0.01). However, using multivariate Cox proportional-hazards regression to adjust for all variables associated with mortality, the influence of beta-blockers became non-significant (HR 0.96; 95% CI: 0.85 to 1.1, p=0.49).. When all variables associated with mortality are considered, none of the cardiovascular agents are associated with the improved survival of patients with suspected HF, raised NT-proBNP but no HF on echocardiography.

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Cardiovascular Agents; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Registries

Background Corin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension. Methods and Results We evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self-identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable-adjusted regression modeling. Multivariable-adjusted genotype-stratified differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and BNP (B-type natriuretic peptide) levels were assessed. Genotype-stratified

Topics: Black People; Blood Pressure; Humans; Hypertension; Longitudinal Studies; Natriuretic Peptide, Brain; Serine Endopeptidases

Topics: Female; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy

Topics: Female; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabol

Topics: Aged; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

Even a slight increase in plasma N-terminal-pro B-type natriuretic peptide (NT-pro BNP) levels is associated with an incremental cardiovascular risk in a healthy cohort. Sacubitril/valsartan has recently been reimbursed in Japan for hypertension. Its impact on reducing plasma NT-pro BNP levels in hypertensive patients remains unknown.. Patients who received 3-month sacubitril/valsartan treatment for their hypertension were retrospectively included. Changes in plasma NT-pro BNP levels during 3-month sacubitril/valsartan therapy (on-treatment period) were compared with those during pre-treatment 3-month period without sacubitril/valsartan (pre-treatment period).. A total of 33 hypertensive patients {73 [64, 77] years old and systolic blood pressure 138 [134, 149] mmHg on median} were included. During a pre-treatment period, systolic blood pressure tended to decrease (P=0.091) whereas plasma NT-pro BNP levels remained unchanged {from 204 [132, 412] to 207 [107, 386] pg/mL, P=0.84}. During on-treatment period, both systolic pressure and plasma NT-pro BNP levels decreased significantly {P<0.001 and P=0.001, respectively, from 207 [107, 386] to 119 [64, 355] pg/mL in NT-pro BNP}. The amount of changes in plasma NT-pro BNP levels during on-treatment period was significantly higher than those during pre-treatment period {-51 [-158, -17] versus -12 [-28, 33] mmHg, P=0.001}.. Plasma NT-pro BNP levels decreased significantly following 3-month sacubitril/valsartan therapy. Its clinical implication requires further long-term studies.

Topics: Aged; Aminobutyrates; Biphenyl Compounds; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Retrospective Studies; Tetrazoles; Valsartan

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11

Topics: Biomarkers; Case-Control Studies; Female; Humans; Hypertension; Interleukin-33; Longitudinal Studies; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Pregnancy; Pregnancy, Twin; Prospective Studies

This research is aimed at analyzing the safety profile and nursing highlights of continuous renal replacement therapy (CRRT) for hypertension (HT) complicated by refractory heart failure (RHF).. Sixty-six HT + RHF patients admitted between March 2018 and December 2021 were enrolled and assigned to two groups: a CRRT group with 33 cases treated with CRRT and a control group with 33 cases intervened by routine treatment. The therapeutic effect and alterations of cardiac function (CF) indexes were observed in both cohorts. Besides, statistics were made in terms of serum B-type natriuretic peptide (BNP), C-reactive protein (CRP) and mean arterial pressure (MAP) concentrations, time of asthma relief, heart rate recovery (HRR), edema resolution, and hospitalization, as well as incidence of adverse reactions (ARs). Finally, pre- and posttreatment psychological quality and pain of both cohorts of subjects were assessed using the self-rating anxiety and depression scale (SAS and SDS) and visual analogue scale (VAS), respectively.. CRRT group exhibited higher overall response rate and better CF than control group (. CRRT can effectively improve the therapeutic effect and CF of patients with HT complicated by RHF, to protect the health and safety of patients.

Topics: Acute Kidney Injury; Asthma; C-Reactive Protein; Continuous Renal Replacement Therapy; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Renal Replacement Therapy

Topics: Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Troponin T

B-type natriuretic peptide (BNP) is a well-established prognostic factor for cardiovascular disorders. However, the association between BNP levels and mortality in patients with acute severe hypertension remains unclear. This study aimed to investigate the association between BNP levels and long-term mortality in patients with acute severe hypertension visiting the emergency department (ED). This retrospective study included patients aged ≥ 18 years who were admitted to the ED between 2016 and 2019 with acute severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg). Patients were categorized into tertiles according to BNP levels upon admission to the ED. Of the 3099 patients with acute severe hypertension, 6.4% in the first (lowest) tertile, 24.8% in the second tertile, and 44.4% in the third (highest) tertile of BNP died within 3-years. After adjusting for clinically relevant variables, patients in the second tertile of BNP (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.96-3.55), and patients in the third tertile of BNP (adjusted HR 4.18; 95% CI, 3.09-5.64) had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP. Therefore, BNP may be valuable for the initial assessment to identify high-risk patients among those with acute severe hypertension.

Topics: Acute Disease; Biomarkers; Emergency Service, Hospital; Humans; Hypertension; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies

Metabolic shift is an important contributory factor for progression of hypertension-induced left ventricular hypertrophy into cardiac failure. Under hypertrophic conditions, heart switches its substrate preference from fatty acid to glucose. Prolonged dependence on glucose for energy production has adverse cardiovascular consequences. It was reported earlier that reactivation of fatty acid metabolism with medium chain triglycerides ameliorated cardiac hypertrophy, oxidative stress and energy level in spontaneously hypertensive rat. However, the molecular mechanism mediating the beneficial effect of medium chain triglycerides remained elusive. It was hypothesized that reduction of cardiomyocyte hypertrophy by medium chain fatty acid (MCFA) is mediated by modulation of signaling pathways over expressed in cardiac hypertrophy. The protective effect of medium chain fatty acid (MCFA) was evaluated in cellular model of myocyte hypertrophy. H9c2 cells were stimulated with Arginine vasopressin (AVP) for the induction of hypertrophy. Cell volume and secretion of brain natriuretic peptide (BNP) were used for assessment of cardiomyocyte hypertrophy. Cells were pretreated with MCFA (Caprylic acid) and metabolic modulation was assessed from the expression of medium-chain acyl-CoA dehydrogenase (MCAD), cluster of differentiation-36 (CD36) and peroxisome proliferator-activated receptor (PPAR)-α mRNA. The signaling molecules modified by MCFA was evaluated from protein expression of mitogen activated protein kinases (MAPK: ERK1/2, p38 and JNK) and Calcineurin A. Pretreatment with MCFA stimulated fatty acid metabolism in hypertrophic H9c2, with concomitant reduction of cell volume and BNP secretion. MCFA reduced activated ERK1/2, JNK and calicineurin A expression mediated by AVP. In conclusion, the beneficial effect of MCFA is possibly mediated by stimulation of fatty acid metabolism and modulation of MAPK and Calcineurin A.

Topics: Animals; Calcineurin; Caprylates; Cardiomegaly; CD36 Antigens; Cell Line; Fatty Acids; Glucose; Hypertension; Hypertrophy; Hypertrophy, Left Ventricular; Lipid Metabolism; Muscle Cells; Natriuretic Peptide, Brain; Oxidative Stress; Rats; Rats, Inbred SHR; Signal Transduction

Chagas disease (ChD) and systemic arterial hypertension (SAH) are two severe comorbidities that lead to mortality and a reduction in people's quality of life, with an impact on public health. The aim of this study was to quantify the biomarkers of cardiac injury in patients with ChD and SAH. Eighty patients were divided into four groups: 20 hypertensive patients, 20 ChD-hypertensive patients, 20 ChD patients, and 20 normotensive volunteers; all of them came from outpatient's public health services. Among the evaluated markers for cardiac lesions (creatine kinase, creatine kinase-MB isoform, myoglobin, high-sensitive cardiac troponin T[hs-cTnT], B-type natriuretic peptide [BNP], and C-reactive protein), hs-cTnT and BNP were the most appropriate. Importantly, our results showed that the cut off point for hs-cTnT could be < 0.007 ng/mL, which could lead to the early detection of myocardial lesions. The BNP and hs-cTnT levels were high only in the ChD and ChD-hypertensive patient groups, suggesting that Chagas' disease may play an important role in the increase of these biomarkers. ChD patients, hypertensive or not, with cardiac or cardiodigestive involvement presented significantly higher values of hs-cTnT (p < 0.001) and BNP (p = 0.001) than ChD patients with indeterminate and digestive forms, which strengthens the validation of these markers for the follow-up of clinical cardiac form of ChD. This study suggests that the BNP and hs-cTnT can be used as possible indirect biomarkers of cardiac damage. In addition, the reference values of these biomarkers in Chagas and hypertensive cardiomyopathies should be better understood with further studies.

Topics: Adult; Aged; Biomarkers; Chagas Disease; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Quality of Life; ROC Curve; Troponin T

The purpose of this study was to establish a nomogram to predict the risk of complicating ventricular tachyarrhythmia (VTA) in patients with acute myocardial infarction (AMI) during hospitalization and to verify the accuracy of the model.. The authors enrolled the information of 503 patients who were diagnosed as AMI from January 2017 to December 2019. The cohort was randomly divided into a training set and a testing set at a ratio of 70%:30%. A total of 13 clinical indicators were screened by the least absolute shrinkage and selection operator (LASSO) regression and Boruta arithmetic independently in order to figure out the optimal feature variables. Multivariable logistic regression analysis was applied to establish the prediction model represented by a nomogram incorporating the selected feature variables. The performance of the nomogram was assessed by discrimination, calibration and clinical usefulness. C-Statistics with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis were used to evaluate the identification ability, calibration and clinical practicability respectively. The prediction model was verified on the testing set to ensure its accuracy.. Five feature variables as percutaneous coronary intervention (PCI) timing after hospitalization, ejection fraction (EF), high-sensitive troponin T (hsTnT) score, infection and estimated glomerular filtration rate (eGFR) were selected by both LASSO regression and Boruta arithmetic. C-statistics with AUC was 0.764 (95% confidence interval: 0.690-0.838) in the training set while a slight increasing to 0.804 (95% confidence interval: 0.673-0.935) in the testing set. Calibration curve illustrated that the predicted and actually diagnosis of VTA probabilities were satisfactory on both training set and testing validation. Decision curve analysis indicated that the nomogram can be used in clinical settings as it has a threshold of between 4% to 90% along with a net benefit.. The nomogram with five variables is practical to clinicians in estimating the risk of complicating VTA after AMI during hospitalization.

Topics: Aged; Diabetes Mellitus; Female; Glomerular Filtration Rate; Humans; Hypertension; Hypokalemia; Infections; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Nomograms; Peptide Fragments; Percutaneous Coronary Intervention; Reproducibility of Results; Retrospective Studies; Risk Assessment; Stroke Volume; Tachycardia, Ventricular; Troponin T; Ventricular Fibrillation

Whether marked nocturnal blood pressure (BP) reduction is associated with cardiovascular disease (CVD) is still controversial. In addition, no report has yet discussed the relationship between lower nocturnal BP and CVD, involving modification by nighttime hypoxia. We evaluated 840 patients who had one or more cardiovascular risk factors by measuring their high-sensitivity cardiac troponin T (Hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), and nighttime saturation levels and performing ambulatory BP monitoring. The lowest tertile in nighttime diastolic BP (DBP) (≤66 mmHg) had increased likelihood of the presence of ≥0.014 ng/ml of Hs-cTnT compared with the second tertile (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.01-3.63), and the lowest tertile of minimum blood oxygen saturation (≤81%) had increased likelihood of the presence of ≥0.014 ng/ml of Hs-cTnT compared with the third tertile (OR 2.15, 95% CI 1.13-4.10). Additionally, the patients with both lowest tertile of nighttime DBP and minimum SpO2 showed increased likelihood of the presence of ≥0.014 ng/ml of Hs-cTnT compared with those without this combination (OR 2.93, 95% CI 1.40-6.16). On the other hand, these associations were not found in the presence of ≥125 pg/ml of NT-pro BNP. In the clinical population, each of lower nocturnal DBP and nighttime hypoxia was associated with asymptomatic myocardial injury, which was represented as higher Hs-cTnT, and coexisting lower nocturnal DBP and nighttime hypoxia had an additive effect on the risk of myocardial injury.

Topics: Biomarkers; Blood Pressure; Humans; Hypertension; Hypoxia; Japan; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Troponin T

Hypertension is a common condition that increases risk for future cardiovascular disease. N-terminal B-type natriuretic peptide (NT-proBNP) is higher in individuals with hypertension, but studies of its association with hypertension risk have been mixed.. The REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 U.S. Black or White adults aged ≥45 years from 2003 to 2007. A subcohort included 4,400 participants who completed a second assessment in 2013-2016. NT-proBNP was measured by immunoassay in 1,323 participants without baseline hypertension, defined as blood pressure ≥140/90 or self-reported antihypertensive prescriptions. Two robust Poisson regression models assessed hypertension risk, yielding incidence rate ratios (IRRs): Model 1 included behavioral and demographic covariates and Model 2 added risk factors. A sensitivity analysis using a less conservative definition of hypertension (blood pressure ≥130/80 or self-reported antihypertensive prescriptions) was conducted.. Four hundred and sixty-six participants developed hypertension after mean follow-up of 9.4 years. NT-proBNP was not associated with hypertension (Model 2 IRR per SD log NT-proBNP 1.01, 95% confidence interval 0.92-1.12), with no differences by sex, body mass index, age, or race. Similar findings were seen in lower-threshold sensitivity analysis.. NT-proBNP was not associated with incident hypertension in REGARDS; this did not differ by race or sex.

Topics: Black People; Female; Heart Disease Risk Factors; Humans; Hypertension; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; United States; White People

During oxidative stress mitochondria become the main source of endogenous reactive oxygen species (ROS) production. In the present study, we aimed to clarify the effects of pharmacological PARP-1 inhibition on mitochondrial function and quality control processes.. L-2286, a quinazoline-derivative PARP inhibitor, protects against cardiovascular remodeling and heart failure by favorable modulation of signaling routes. We examined the effects of PARP-1 inhibition on mitochondrial quality control processes and function in vivo and in vitro. Spontaneously hypertensive rats (SHRs) were treated with L-2286 or placebo. In the in vitro model, 150 μM H. PARP-inhibition prevented the development of left ventricular hypertrophy in SHRs. The interfibrillar mitochondrial network were less fragmented, the average mitochondrial size was bigger and showed higher cristae density compared to untreated SHRs. Dynamin related protein 1 (Drp1) translocation and therefore the fission of mitochondria was inhibited by L-2286 treatment. Moreover, L-2286 treatment increased the amount of fusion proteins (Opa1, Mfn2), thus preserving structural stability. PARP-inhibition also preserved the mitochondrial genome integrity. In addition, the mitochondrial biogenesis was also enhanced due to L-2286 treatment, leading to an overall increase in the ATP production and improvement in survival of stressed cells.. Our results suggest that the modulation of mitochondrial dynamics and biogenesis can be a promising therapeutical target in hypertension-induced myocardial remodeling and heart failure.

Topics: Animals; Cells, Cultured; Citrate (si)-Synthase; DNA, Mitochondrial; Electrocardiography; Glutathione; Hypertension; Hypertrophy, Left Ventricular; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Proteins; Myocytes, Cardiac; Natriuretic Peptide, Brain; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Quinazolines; Rats, Inbred SHR; Rats, Wistar

Studies of cardiovascular function in pregnancy have shown inconsistent and, in some cases, contradictory results, particularly regarding cardiac output. While some studies report preeclampsia associated with high cardiac output, other studies suggest that preeclampsia should be further subdivided into women with high or low cardiac output. This study was conducted to examine the NT-proBNP levels in preeclampsia, intrauterine growth restriction, and hypertensive pregnancies without preeclampsia. We also examined N-terminal pro-B natriuretic peptide (NT-proBNP) levels three to four months after delivery, in preeclamptic women as well as the prediction of delivery within 10 days. In a reduced number of preeclamptic women and controls we performed echocardiograms to study their diastolic function.. We investigated the NT-proBNP levels in 213 subjects with preeclampsia only, 73 with intrauterine growth restriction, 44 with preeclampsia and intrauterine growth restriction, 211 who were hypertensive and 662 unaffected pregnancies (controls). We also performed echocardiograms on 36 preeclampsia and 19 controls before delivery and three to five months after delivery.. NT-proBNP levels are higher in early onset preeclampsia than in late onset preeclampsia. Intrauterine growth restriction pregnancies showed a NT-proBNP levels similar to hypertensive and unaffected pregnancies. Compared with healthy pregnancies, women with preterm preeclampsia (<37 gestational weeks) had altered left atrial segments.. We observed that NT-proBNP levels are higher in early onset preeclampsia than in late onset. Moreover, diastolic dysfunction is higher in early onset than in late-onset term preeclampsia. An NT-proBNP value >136 pg/mL has a high positive predictive value for an imminent delivery within 10 days.

Topics: Biomarkers; Female; Fetal Growth Retardation; Humans; Hypertension; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Pregnancy

Heart failure (HF) is a complex chronic clinical disease characterized by among others the damage of the mitochondrial network. The disruption of the mitochondrial quality control and the imbalance in fusion-fission processes lead to a lack of energy supply and, finally, to cell death. BGP-15 (O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic acid amidoxime dihydrochloride) is an insulin sensitizer molecule and has a cytoprotective effect in a wide variety of experimental models. In our recent work, we aimed to clarify the mitochondrial protective effects of BGP-15 in a hypertension-induced heart failure model and "in vitro." Spontaneously hypertensive rats (SHRs) received BGP-15 or placebo for 18 weeks. BGP-15 treatment preserved the normal mitochondrial ultrastructure and enhanced the mitochondrial fusion. Neonatal rat cardiomyocytes (NRCMs) were stressed by hydrogen-peroxide. BGP-15 treatment inhibited the mitochondrial fission processes, promoted mitochondrial fusion, maintained the integrity of the mitochondrial genome, and moreover enhanced the de novo biogenesis of the mitochondria. As a result of these effects, BGP-15 treatment also supports the maintenance of mitochondrial function through the preservation of the mitochondrial structure during hydrogen peroxide-induced oxidative stress as well as in an "in vivo" heart failure model. It offers the possibility, which pharmacological modulation of mitochondrial quality control under oxidative stress could be a novel therapeutic approach in heart failure.

Topics: Animals; Animals, Newborn; Cell Culture Techniques; Citrate (si)-Synthase; DNA; DNA Damage; DNA, Mitochondrial; Dynamins; Electron Transport; Energy Metabolism; Genome, Mitochondrial; Heart Failure; Hypertension; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Dynamics; Mitochondrial Proteins; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organelle Biogenesis; Oxidative Stress; Oximes; Oxygen Consumption; Piperidines; Rats, Inbred SHR; Rats, Inbred WKY

We tested the hypothesis that angiotensin II (Ang II)-induced cardiovascular complications are distinguished from what catecholamine-induced by their serum circulating biomarkers in rats. Infusion of Ang II (1.68 mg/kg/day) significantly increased systolic and diastolic blood pressure assessed at week one or later, accompanied by an increase of heart/body weight ratio. Noradrenaline infusion (5.40 mg/kg/day) produced a similar degree of hypertension, but did not increase heart weight. Ang II-, but not noradrenaline-induced hypertension was associated with a drastic upregulation of serum microRNA-30d (miR-30d) by hundreds of times, accompanied by an increase of miR-30d levels in the atrium but not in the ventricle. Ang II, but not noradrenaline, significantly increased mRNA of brain natriuretic peptide (BNP) in the atrium. Studies using rat neonatal cardiomyocytes in vitro demonstrated that BNP caused an increase of miR-30d when applied for 6 h or longer in the culture medium. In vitro application of Ang II increased the cell size, although BNP and miR-30d were unable to mimic the effect of Ang II. We conclude that serum circulating microRNA-30d is a sensitive biomarker for Ang II-induced cardiovascular complications. It is also postulated that Ang II-induced cardiomyocyte hypertrophy could be independent of miR-30d/BNP signaling pathways.

Topics: Angiotensin II; Animals; Biomarkers; Cardiomegaly; Hypertension; MicroRNAs; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats

Topics: Biomarkers; Case-Control Studies; Female; Humans; Hypertension; Infant, Low Birth Weight; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Trimester, First; Prognosis; Prospective Studies; Tertiary Care Centers

Pentraxin 3 (PTX3) is synthesized locally and released into the circulation, reflecting local inflammation in the cardiovascular system. Therefore, we conducted a study to explore the effect of PTX3 in spontaneously hypertensive heart failure (SHHF) rats. Sprague Dawley (SD) and SHHF rats were treated with recombinant PTX3 protein, and the blood pressure (BP) and echocardiographic parameters were collected. Radioimmunoassay, enzyme immunoassay and enzyme-linked immunosorbent assay (ELISA) were applied to detect plasma levels of atrial/B-type natriuretic peptide (ANP/BNP) and PTX3. The pathological changes in the myocardial tissues were observed by hematoxylin and eosin (HE) and Masson stainings. The mRNA and protein expressions were detected by quantitative real-time reverse-transcription polymerase chain reaction (qPCR) and western blotting. Cardiomyocyte apoptosis was evaluated by TUNEL staining and DNA fragmentation test. Increased plasma concentrations of PTX3 were found in SHHF rats compared with SD rats, which was further enhanced by recombinant PTX3 protein. After injection with recombinant PTX3 protein, the heart function was improved in SHHF rats with the decreased systolic and diastolic BP, and the reduced plasma levels of ANP and BNP. Moreover, PTX3 improved the myocardial damage and interstitial fibrosis in SHHF rats with reduced cardiomyocyte apoptosis and decreased mRNA expressions of pro-inflammatory factors in myocardial tissues. PTX3 could decrease the BP and plasma levels of ANP and BNP in SHHF rats, as well as improve the inflammation, cardiomyocyte apoptosis, and pathological changes of myocardial tissues, suggesting it may be a useful intervention in the treatment of SHHF.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Pressure; C-Reactive Protein; Cytokines; Disease Models, Animal; Heart Failure; Hypertension; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats, Inbred SHR; Rats, Sprague-Dawley; Recombinant Proteins; Serum Amyloid P-Component; Ventricular Function, Left

N-terminal pro B-type natriuretic peptide (NT-proBNP), a cardiac disease biomarker, has been demonstrated to be a strong independent predictor of cardiovascular events in patients without heart failure. Patients with peripheral arterial disease (PAD) are at high risk of cardiovascular events and death. In this study, we investigated levels of NT-proBNP in patients with PAD compared to non-PAD controls. A total of 355 patients were recruited from outpatient clinics at a tertiary care hospital network. Plasma NT-proBNP levels were quantified using protein multiplex. There were 279 patients with both clinical and diagnostic features of PAD and 76 control patients without PAD (non-PAD cohort). Compared with non-PAD patients, median (IQR) NT-proBNP levels in PAD patients were significantly higher (225 ng/L (120-363) vs 285 ng/L (188-425), p- value = 0.001, respectively). Regression analysis demonstrated that NT-proBNP remained significantly higher in patients with PAD relative to non-PAD despite adjusting for age, sex, hypercholesterolemia, smoking and hypertension [odds ratio = 1.28 (1.07-1.54), p-value <0.05]. Subgroup analysis showed elevated NT-proBNP levels in patients with PAD regardless of prior history of CHF, CAD, diabetes and hypercholesteremia (p-value <0.05). Finally, spearmen's correlation analysis demonstrated a negative correlation between NT-proBNP and ABI (ρ = -0.242; p-value < 0.001). In conclusion, our data shows that patients with PAD in an ambulatory care setting have elevated levels of NT-proBNP compared to non-PAD patients in the absence of cardiac symptoms.

Topics: Aged; Comorbidity; Diabetes Mellitus; Female; Heart Diseases; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatient Clinics, Hospital; Outpatients; Peptide Fragments; Peripheral Arterial Disease; Smoking

Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey.. The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control.. N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN.. The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Diuretics; Drug Combinations; Female; Furosemide; Glycated Hemoglobin; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Retrospective Studies; Stroke Volume; Turkey; Valsartan; Ventricular Dysfunction, Left

Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors.. A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension.. Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels.. ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Topics: Age Factors; Aged; Atrial Fibrillation; Case-Control Studies; Female; Heart Atria; Heart Rate; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Hormones; Regression Analysis; Risk Factors

Plasma N-terminal pro brain natriuretic peptide (NT-proBNP) and R wave in aVL lead (RaVL) have been associated with mortality in hypertension. The aim of the current study was to compare the prognostic value of their combination to that of the left ventricular mass index (LVMI) assessed by echocardiography.. A total of 1104 hypertensive patients who had at baseline an assessment of plasma NT-proBNP, a 12-lead ECG, and echocardiography were included. LVMI was assessable in 921 patients. After a median (interquartile range) follow-up of 8.5 (5.4-13.3) years, 110 deaths occurred, 62 of which were from a cardiovascular cause.. Optimal thresholds of RaVL and plasma NT-proBNP to predict mortality were 0.7 mV and 150 pg/ml, respectively. A three-modality variable based on RaVL and NT-proBNP was built: 0 when none were above the threshold, 1 or 2 when only one or both were above the threshold. After adjustment for all confounders including LVMI indexed to height raised to the allometric power of 2.7 in Cox regression analysis, we observed a significant increased risk for patients having one marker above the threshold for all-cause and cardiovascular mortality [hazard ratio: 1.76; 95% confidence interval (1.08-2.86); 2.18 (1.06-4.46)] and for those having two markers above the threshold [2.76 (1.51-5.03); 3.90 (1.69-9.00)]. The prognostic value of the combination had the highest C-index (0.772 and 0.839, respectively) in comparison with LVMI (0.746 and 0.806, respectively).. Risk stratification in hypertension using the combination of NT-proBNP and RaVL is a simple method that may be considered in first line screening.

Topics: Echocardiography; Electrocardiography; Follow-Up Studies; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment

Objective Numerous studies have reported an association between common carotid artery (CCA) parameters and atherosclerotic cardiovascular disease (CVD). However, the association between CCA parameters and hemodynamic stress on the left ventricle in elderly patients remains unclear. Methods We assessed CCA parameters, including the height-adjusted CCA interadventitial diameter (diameter/height), mean intima-media thickness (IMT), number of plaques, plaque score, resistance index (RI), and pulsatility index (PI) with ultrasonography, using serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels as a marker for hemodynamic stress on the left ventricle in 1,315 participants ≥70 years old without CVD. Of these participants, 706 had hypertension, defined as taking antihypertensive medications, having a systolic blood pressure ≥140 mmHg, and/or having a diastolic blood pressure ≥90 mmHg. Results After adjusting for the confounding factors, the CCA interadventitial diameter/height was significantly associated with the log NT-proBNP in both the normotensive group (β=0.125, p=0.002) and hypertensive group (β=0.080, p=0.029). The RI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.176, p<0.001) but not in the normotensive group. In addition, the PI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.156, p<0.001) but not in the normotensive group. However, no significant association was observed between the mean IMT, number of plaques, and plaque score and log NT-proBNP. Conclusion CCA measurements may be useful markers for hemodynamic stress on the left ventricle in elderly patients.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Blood Pressure; Carotid Intima-Media Thickness; Female; Heart Ventricles; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments

Pulmonary hypertension (PH) has been described in myelofibrosis (MF), but it is rare and typically found in advanced disease. Although the etiology of PH in MF is unclear, early predictors may be detected by echocardiogram. The goals of our study were to evaluate the prevalence of PH as determined by echocardiography in a cohort of MF patients and to identify clinical risk factors for PH. We performed a retrospective review of MF patients from October 2015 to May 2017 at MD Anderson Cancer Center in the ambulatory clinic, and those with echocardiogram were included. Clinical, echocardiographic, and laboratory data were reviewed. Patients with and without PH were compared using a chi-square or Fisher's exact test, and logistic regression was performed with an outcome variable of PH. There were 143 patients with MF who underwent echocardiogram, and 20 (14%) had echocardiographic findings consistent with PH. Older age, male gender, hypertension, hyperlipidemia, coronary artery disease, dyspnea, hematocrit, brain natriuretic peptide (BNP), and N-terminal prohormone BNP (NT-proBNP) were significantly different between those without PH and those with PH (p < 0.05). Female gender was protective (OR 0.21, 95% CI 0.049-0.90, p = 0.035), and NT-proBNP was a significant clinical predictor of PH (OR 1.07, CI 1.02 = 1.12, p = 0.006). PH in MF is lower than previously reported in our MF cohort, but many patients had cardiac comorbidities. PH due to left-sided heart disease may be underestimated in MF. Evaluation of respiratory symptoms and elevated NT-proBNP should prompt a baseline echocardiogram. Early detection of PH with a multidisciplinary approach may allow treatment of reversible etiologies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Comorbidity; Coronary Disease; Dyspnea; Echocardiography; Female; Humans; Hyperlipidemias; Hypertension; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Primary Myelofibrosis; Retrospective Studies; Young Adult

We hypothesized that the association between the dipping heart rate (HR) pattern and cardiovascular (CV) events differs according to the brain natriuretic peptide (BNP) level.. We examined a subgroup of 1,369 patients from the Japan Morning Surge Home Blood Pressure study; these were patients who had CV risk factors and had undergone ambulatory blood pressure (BP) monitoring. HR non-dipping status was defined as (awake HR - sleep HR)/awake HR <0.1, and high BNP was defined as ≥35 pg/ml. We divided the patients into four groups according to their HR dipper status (dipping or non-dipping) and BNP level (normal or high).. The mean follow-up period was 60 ± 30 months. The primary endpoints were fatal/nonfatal CV events (myocardial infarction, angina pectoris, stroke, hospitalization for heart failure, and aortic dissection). During the follow-up period, 23 patients (2.8%) in the dipper HR with normal BNP group, 8 patients (4.4%) in the non-dipper HR with normal BNP group, 24 patients (9.5%) in the dipper HR with high-BNP group, and 25 patients (21.0%) in the non-dipper HR with high-BNP group suffered primary endpoints (log rank 78.8, P < 0.001). Non-dipper HR was revealed as an independent predictor of CV events (hazard ratio, 2.13; 95% confidence interval, 1.35-3.36; P = 0.001) after adjusting for age, gender and smoking, dyslipidemia, diabetes mellitus, chronic kidney disease, BNP, non-dipper BP, 24-h HR, and 24-h systolic blood pressure.. The combination of non-dipper HR and higher BNP was associated with a higher incidence of CV events.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiovascular Diseases; Circadian Rhythm; Female; Heart Disease Risk Factors; Heart Rate; Humans; Hypertension; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Time Factors

Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali).. We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests.. Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q. We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.

Topics: Adult; Case-Control Studies; Female; Humans; Hyperhomocysteinemia; Hypertension; Male; Mali; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Risk Factors

We aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), brain natriuretic peptide (BNP), and left ventricular hypertrophy (LVH) in hypertension.. This study included 386 patients with hypertension. Mann-Whitney U test and multivariate binary logistic regression analysis were used to investigate the relationship between NLR, CRP, BNP, and LVH in patients with hypertension, as well as compare the levels of NLR, CRP, and BNP in the four configurations. Receiver operator characteristic (ROC) curve was used to compare the diagnostic efficacy of NLR, CRP, and BNP on LVH.. The NLR and CRP and BNP levels of the LVH group were significantly higher than those of the non-LVH group. In the multivariate logistic regression analysis, NLR as well as age, BMI, and SBP were associated with LVH. In addition, in patients with eccentric and concentric hypertrophy, the NLR and CRP and BNP levels were higher than those of the normal left ventricular geometry and concentric remodeling groups. The cutoff values of NLR, CRP, and BNP obtained by ROC curve were 2.185, 2.205, and 283.45, respectively, for the prediction of LVH.. NLR is independently associated with LVH in patients with hypertension, and this is consistent with the diagnostic efficacy of CRP and BNP, which may be a simple and convenient indicator for judging LVH.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Lymphocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain

The aim of our research was to evaluate the relationship involving left ventricular ejection fraction, low density lipoprotein, B-type natriuretic peptide, Troponin I and coronary flow reserve, and to determine the predictors of left ventricular ejection fraction in patients with coronary microvascular disease and obstructive coronary artery disease, and in patients with coronary microvascular disease.. The mean age was 58.5 ± 12.5 years. In patients with obstructive coronary disease and coronary microvascular disease we found low density lipoprotein-c had significant inverse relationship with left ventricular ejection fraction, left ventricular ejection fraction also had significant negative relationship with B-type natriuretic peptide, and Troponin-I. While a significant direct relationship turned out to be observed linking left ventricular ejection fraction with coronary flow reserve. Left ventricular ejection fraction had significant negative relationship with low density lipoprotein, and B-type natriuretic peptide in patients with obstructive coronary artery disease only. Age, blood pressure, lipid levels, red cell distribution width, glycated hemoglobin, symptoms, New York heart association classification, alcohol drinking, hypertension, diabetes mellitus, troponin levels and B-type natriuretic peptide were the predictors for left ventricular ejection fraction in coronary microvascular disease patients.

Topics: Alcohol Drinking; Cholesterol, LDL; Coronary Artery Disease; Coronary Circulation; Diabetes Mellitus; Female; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Troponin I; Ventricular Function, Left

Topics: Echocardiography; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment

Topics: Echocardiography; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment

Increased blood pressure (BP) variability, an index of hemodynamic stress, leads to cardiac overload and worse cardiovascular prognosis. The association between day-by-day home BP variability and NT-proBNP (N-terminal pro-B-type natriuretic peptide) as an index of cardiac overload may be amplified by increased arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV). J-HOP (Japan Morning Surge-Home Blood Pressure) Study participants who were selected from a practitioner-based population with at least one cardiovascular risk factor underwent home BP monitoring, and their BP levels and SD, coefficient of variation, and average real variability as indexes of systolic BP variability were assessed. We analyzed 2115 individuals without prevalent heart failure and divided them into lower (<1800 cm/s, n=1464) and higher (≥1800 cm/s, n=651) baPWV groups. The higher baPWV group had significantly higher SD

Topics: Aged; Analysis of Variance; Ankle Brachial Index; Blood Pressure Monitoring, Ambulatory; Cardiovascular System; Correlation of Data; Female; Heart Disease Risk Factors; Humans; Hypertension; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Vascular Stiffness

Hypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF.. Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmö Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1-48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P < 3.4E-4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P < 0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 ≤ HR ≤ 1.49, P ≤ 4.90E-3]. GDF-15 and IL-6 were associated with HF independently of each other (1.22 ≤ HR ≤ 1.33, P ≤ 0.001). In subjects with hypertension, these associations remained significant after further adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1.23 ≤ HR ≤ 1.45, P ≤ 0.001). A higher fasting value of a GDF-15, IL-6 score aggregate was associated with increased risk of hypertensive HF after adjustment for all traditional risk factors for HF and NT-proBNP (HR = 1.31, P = 2.19E-4).. Cardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers.

Topics: Animals; Biomarkers; Heart Failure; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Rats

This study aimed to explore the correlation of serum brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels with cardiac pump function and ventricular remodeling in patients with heart failure. Eighty-one patients with chronic heart failure admitted to our hospital from March 2016 to November 2018 were enrolled as the study group, and 80 healthy individuals as the control group. Immunofluorescence was used for the detection of serum BNP, ELISA for serum ET-1, and ultrasound for related indexes of cardiac pump function and ventricular remodeling. Moreover, correlation analysis and prognostic factors analysis were carried out. Both BNP and ET-1 were highly expressed in the serum of patients with heart failure. Cardiac pump function related indexes (left atrial ejection fraction (LAEF), left atrial passive ejection fraction (LAPEF), and left atrial active ejection fraction (LAAEF)) in the study group were significantly lower than those in the control group (P< 0.05). While ventricular remodeling related indexes (left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPM), and left ventricular mass index (LVMI) in the study group were significantly higher than those in the control group (P< 0.05). BNP and ET-1 were negatively correlated with LAEF, LAPEF and LAAEF (P< 0.05), and were positively correlated with LVEDD, IVST, LVPM and LVMI (P< 0.05). The expressions of serum BNP and ET-1 were higher in patients with cardiovascular events than those without cardiovascular events. Hypertension, hyponatremia, high BNP, high ET-1, NYHA classification, decreased LAEF and increased LVEDD were independent risk factors for cardiovascular adverse events. Serum BNP and ET-1 are closely related to cardiac pump function and ventricular remodeling in patients with heart failure and can be used as important reference indexes for prognosis evaluation.

Topics: Endothelin-1; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Ventricular Remodeling

This was an investigation of the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and mortality in patients with stage 3-4 chronic kidney disease (CKD).. This study was designed as a subgroup analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) study. The HAPPY study included 4650 randomly selected individuals from the 7 geographical regions of Turkey. A total of 191 subjects from the original cohort with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.1.73 m² were enrolled in this study and the relationship between NT-proBNP and mortality was investigated. Prognostic variables for total and cardiovascular mortality were also examined using Cox regression analysis.. The mean length of follow-up was 76.12±22.45 months. The mean NT-proBNP level was 423.54±955.88 pg/mL. During follow-up, 51 subjects (26.7%) died from any cause and 36 subjects (18.8%) died from a cardiovascular cause. The presence of hypertension (hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.01-3.50; p=0.048), anemia (HR: 2.49; 95% CI: 1.20-5.15; p=0.014), male gender (HR: 2.64; 95% CI: 1.44-4.86; p=0.002) and log NT-proBNP (HR: 4.93; 95% CI: 2.83-8.58; p<0.001) were independent variables for total mortality. The presence of hypertension (HR: 2.47; 95% CI: 1.09-5.56; p=0.029), male gender (HR: 2.79; 95% CI: 1.38-5.62; p=0.004), eGFR (HR: 0.94; 95% CI: 0.91-0.98; p=0.005) and log NT-proBNP (HR: 6.31; 95% CI: 3.11-12.81; p<0.001) were independent predictors of cardiovascular mortality.. NT-proBNP was found to be an independent prognostic marker in patients with stage 3-4 CKD.

Topics: Aged; Anemia; Biomarkers; Cause of Death; Confidence Intervals; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Regression Analysis; Renal Insufficiency, Chronic; Sex Factors; Turkey

Assessment of the plasma concentrations of natriuretic peptides (NPs) is widely used to diagnose and evaluate the progression of cardiac failure, and their potential as markers of preeclampsia (PE) has been examined in recent years. It has been established that plasma concentrations of NPs do not change in the course of normal pregnancy. However, elevated levels of these peptides may have a prognostic value in patients with PE. This study presents information about the relevance of NPs assessment in the evaluation of physiological pregnancy, as well as in pregnancy complicated with arterial hypertension. The most commonly examined NPs is the N-terminal fragment of the brain natriuretic peptide (NT-proBNP), and it may be prognostic marker of PE and other complications of pregnancy.

Topics: Adult; Biomarkers; Female; Gestational Age; Humans; Hypertension; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnant Women

A new virus broke out in Wuhan, Hubei, China, that was later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical characteristics of severe pneumonia caused by SARS-CoV-2 are still not clear.. The aim of this study was to explore the clinical characteristics and risk factors of severe pneumonia caused by the SARS-CoV-2 in Wuhan, China.. The study included patients hospitalized at the Central Hospital of Wuhan who were diagnosed with COVID-19. Clinical features, chronic comorbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of patients with severe pneumonia caused by SARS-CoV-2.. A total of 110 patients diagnosed with COVID-19 were included in the study, including 38 with severe pneumonia and 72 with nonsevere pneumonia. Statistical analysis showed that advanced age, increased D-Dimer, and decreased lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with severe pneumonia showed that the illness can progress rapidly.. Advanced age, decreased lymphocytes, and D-Dimer elevation are important characteristics of patients with severe COVID-19. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.

Topics: Adult; Age Factors; APACHE; Betacoronavirus; C-Reactive Protein; China; Comorbidity; Coronavirus Infections; Cough; COVID-19; Disease Progression; Dyspnea; Fatigue; Female; Fever; Fibrin Fibrinogen Degradation Products; Humans; Hypertension; Lung; Lymphocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Dysfunction Scores; Pandemics; Pneumonia, Viral; Procalcitonin; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Risk Assessment; SARS-CoV-2; Serum Albumin; Severity of Illness Index; Sex Factors; Tomography, X-Ray Computed

The composite Model for End-Stage Liver Disease Excluding International Normalized Ratio Score (MELD-XI) is a novel tool to evaluate cardio-renal and cardio-hepatic interactions in patients with advanced heart failure (HF). However, its prognostic ability remains unclear in elderly HF patients.. From July 2014 to July 2018, patients hospitalized for HF were prospectively recruited at 16 centers. Clinical features, laboratory findings, and echocardiography results were assessed prior to discharge. Cardiovascular (CV) death and HF re-hospitalization were recorded. Of the 676 patients enrolled, 264 (39.1%) experienced CV events throughout a 1-year median follow-up period. Patients with high MELD-XI were predominantly male and had a higher prevalence of NYHA III/IV, history of HF admission, hyperuricemia, ventricular tachycardia, anemia, and ischemic heart disease. In Kaplan-Meyer analysis, patients with higher MELD-XI (≥11) scores showed a worse prognosis than did those with lower (<11) scores (log-rank p≤0.001). Multivariate Cox proportional hazards testing revealed MELD-XI as an independent predictor of CV events (HR: 1.033, 95% CI: 1.006-1.061, p = 0.015) after adjusting for age, gender, body mass index, NYHA III/IV, prior HF hospitalization, systolic blood pressure, ischemic etiology, ventricular tachycardia, anemia, BNP, and left ventricular ejection fraction.. Cardio-renal and cardio-hepatic interactions predicted CV events in aged HF patients.

Topics: Aged; Aged, 80 and over; Anemia; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Electrocardiography; Female; Heart Failure; Humans; Hypertension; Kaplan-Meier Estimate; Liver; Male; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Ventricular Function, Left

Acute pulmonary embolism (APE) is a major cause of death from cardiovascular disease. Right ventricular systolic dysfunction (RVD) caused by APE is closely related to a poor outcome. Early risk stratification of APE is a vital step in prognostic assessment. The objective of this study was to investigate the usefulness of computed tomographic pulmonary angiography (CTPA) measured right ventricular (RV)/ left ventricular (LV) diameter ratio by the emergency department (ED) specialists for early risk stratification of APE patients in ED.. The retrospective data of 229 APE patients were reviewed. Two ED specialists measured both RV and LV diameters on a single transverse scan perpendicular to the long axis of the heart. The patients were divided into two groups, RV/LV diameter ratio <1 and ratio >1. CTPA measured RV/LV diameter ratio were analyzed and compared with sPESI score, cardiac biomarkers such as N-Terminal Pro-B-Type Natriuretic Peptide (NT-pro-BNP), high sensitivity cardiac troponin T (hs-cTnT), and RVD measured by echocardiography (Echo).. The mean age in RV/LV > 1 group was significantly higher than that of the other group (67.81±2.7 years vs. 60.68±3.2 years). Also, there were more hypertension patients (44.4% vs. 33.3%), and mean arterial pressure (MAP) was lower. A significantly higher ICU admission rate (28.05% vs. 11.61%) was shown in RV/LV >1 group, and five patients expired only in RV/LV > 1 group. RVD by Echo demonstrated the highest sensitivity, specificity, and negative predictive value (NPV) (values of 94.3%, 81.1%, 95.5%). RV/LV >1 diameter ratio by CTPA showed usefulness equivalent to cardiac biomarkers. RV/LV >1 patients' cardiac enzymes were higher, and there were more RVD in RV/LV >1 group.. Simple measurement of RV/LV diameter ratio by ED specialist would be a help to the clinicians in identifying and stratifying the risk of the APE patients presenting in the ED.

Topics: Aged; Biomarkers; Computed Tomography Angiography; Echocardiography; Emergency Medical Services; Emergency Service, Hospital; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method; Symptom Assessment; Troponin T

Visceral fat area (VFA) is a good surrogate marker of obesity-related disorders, such as hypertension, dyslipidemia and glucose intolerance. Although estimating the VFA by X-ray computed tomography (CT) is the primary index for visceral obesity, it is expensive and requires invasive radiation exposure. Dual bioelectrical impedance analysis (BIA) is a simple and reliable method to estimate VFA; however, the clinical usefulness of dual BIA remains unclear in patients with type 2 diabetes (T2D).. We estimated the VFAs by dual BIA and CT in 98 patients with T2D and assessed anthropometric parameters, blood test results, and the presence of comorbid hypertension and dyslipidemia. We compared the correlation between the VFAs examined by dual BIA and CT. Furthermore, we performed the receiver operating characteristic (ROC) analyses for the VFAs to detect the presence of comorbid hypertension and/or dyslipidemia with T2D, which are major comorbidities of visceral obesity, and estimated the area under the curve (AUC).. The measurement error between the VFAs by dual BIA and CT was significantly higher among patients with brain natriuretic peptide (BNP) ≥ 100 pg/mL than those with BNP < 100 pg/mL (39.2% ± 31.1% vs. 24.1% ± 18.6%, P < 0.05). After excluding patients with BNP ≥ 100 pg/mL, the VFA by dual BIA significantly correlated with the VFA by CT (r = 0.917; P < 0.0001). The AUC in the ROC analysis for the VFA by dual BIA to detect the presence of comorbid hypertension and/or dyslipidemia with T2D was almost equivalent to that for the VFA by CT.. In patients with T2D without elevated BNP > 100 pg/mL as indicator for fluid accumulation interfering with BIA, estimation of the VFA by dual BIA significantly correlated with that by CT and also detected comorbid hypertension and/or dyslipidemia with T2D equivalent to those detected by CT. Hence, dual BIA could be an alternative to CT as a standard method for estimating the VFA in patients with diabetes.

Topics: Adiposity; Aged; Biomarkers; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Dyslipidemias; Electric Impedance; Female; Humans; Hypertension; Intra-Abdominal Fat; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prevalence; Reproducibility of Results; Risk Factors; Tomography, X-Ray Computed

The aim of the present study was to evaluate the usefulness of serum B-type natriuretic peptide (BNP) as a biomarker of fluid retention in hypertensive children on peritoneal dialysis (PD).. Hypertensive children on PD were included. The changes (∆) of body weight (BWt), blood pressure (BP) and serum BNP at initial and follow-up periods were reviewed. Data are presented as mean ± standard deviation (median, minimum - maximum). Wilcoxon signed-rank test was used to evaluate the changes in BWt, BP, and BNP. Linear regression analysis was applied for the correlation between the changes of BNP and BP.. A total of 56 hypertensive events were evaluated in 30 patients. Initial findings were BWt 30.5 ± 22.4 (26.5, 3.0-93.5) kg, systolic BP (SBP) 153.3 ± 21.5 (150, 110-241) mmHg, diastolic BP (DBP) 100.1 ± 22.3, (99.5, 49-181) mmHg, BNP 3579.3 ± 6328.9 (1198.5, 305-22 028) pg/mL. Follow-up results were BWt 29.1 ± 21.3 (25.0, 3.12-86) kg, SBP 116.4 ± 17.8 (117.5, 82-150) mmHg, DBP 73.3 ± 14.2 (75.0, 42.0-101.0) mmHg, BNP 63.5 ± 49.2 (60.5, 2-261) pg/mL. ∆SBP (-23.1 ± 13.8, -22.8, -46.9 - 22.5%, P < 0.001), ∆DBP (-24.1 ± 19.2, -24.7, -55.6 - 23.2%, P < 0.001) and ∆BNP (-93.5 ± 8.1, -96.7, -99.9 - -61.0%, P < 0.001) dropped significantly after reduction of ∆BWt (-4.8 ± 4.7, -4.8, -18.7 - 5.6%, P < 0.001). The ∆BNP were significantly correlated with ∆SBP (adjusted R square = 0.221, P < 0.001) and ∆DBP (adjusted R square = 0.203, P < 0.001).. Serum B-type natriuretic peptide should be measured in hypertensive patients on PD to evaluate the volume status.

Topics: Biomarkers; Blood Pressure Determination; Child; Correlation of Data; Female; Fluid Shifts; Humans; Hypertension; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Peritoneal Dialysis; Republic of Korea; Water-Electrolyte Imbalance

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Protein Precursors; Retrospective Studies; Stroke Volume; Turkey; Ventricular Function, Left; Young Adult

Recent clinical studies have demonstrated that serum fibroblast growth factor 23 (FGF23) levels have a significant association with left ventricular hypertrophy (LVH). Although LVH is commonly seen in hypertensive patients, the association between FGF23, hypertension, and LVH remains unclear. We aimed to examine the changes in serum and intracardiac FGF23 during the progression of hypertension using spontaneously hypertensive rats (SHR).. Male SHR comprised the experimental group (HT group) and Wistar Kyoto rats served as controls. At 10 weeks, urinary and blood biochemical analyses and blood pressure measurements were performed for both the groups. At 18 weeks, the rats were sacrificed: urinary and blood biochemical analyses and real-time PCR were performed.. At 18 weeks, the relative heart weight and serum N-terminal pro-brain natriuretic peptide and aldosterone levels were significantly greater in the HT group. Serum calcium and phosphate levels were significantly lower, while serum FGF23 levels were significantly higher in the HT group compared to the control group. Further analyses showed that the mRNA expression of FGF23 in the heart was significantly increased in the HT group compared to the control group. Both serum FGF23 levels and intracardiac mRNA expression of FGF23 showed significant correlation with the relative heart weight.. During LVH progression, serum and intracardiac FGF23 increased in hypertension. Although it is unclear whether the change in FGF23 is the cause or result of LVH, the interaction between FGF23 and aldosterone may be associated with the development of LVH in hypertension.

Topics: Aldosterone; Animals; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Models, Animal; Fibroblast Growth Factors; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Rats, Inbred SHR; Rats, Inbred WKY

Topics: Adult; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Male; Middle Aged; Muscle Cells; Natriuretic Peptide, Brain; Peptide Fragments; South Africa; Troponin T; Tumor Necrosis Factor-alpha; Young Adult

This study investigates differences between women and men in heart failure (HF) risk and mortality.. Sex differences in HF epidemiology are insufficiently understood.. In 78,657 individuals (median 49.5 years of age; age range 24.1 to 98.7 years; 51.7% women) from community-based European studies (FINRISK, DanMONICA, Moli-sani, Northern Sweden) of the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium, the association between incident HF and mortality, the relationship of cardiovascular risk factors, prevalent cardiovascular diseases, biomarkers (C-reactive protein [CRP]; N-terminal pro-B-type natriuretic peptide [NT-proBNP]) with incident HF, and their attributable risks were tested in women vs. men.. Over a median follow-up of 12.7 years, fewer HF cases were observed in women (n = 2,399 [5.9%]) than in men (n = 2,771 [7.3%]). HF incidence increased markedly after 60 years of age, initially with a more rapid increase in men, whereas incidence in women exceeded that of men after 85 years of age. HF onset substantially increased mortality risk in both sexes. Multivariable-adjusted Cox models showed the following sex differences for the association with incident HF: systolic blood pressure hazard ratio (HR) according to SD in women of 1.09 (95% confidence interval [CI]: 1.05 to 1.14) versus HR of 1.19 (95% CI: 1.14 to 1.24) in men; heart rate HR of 0.98 (95% CI: 0.93 to 1.03) in women versus HR of 1.09 (95% CI: 1.04 to 1.13) in men; CRP HR of 1.10 (95% CI: 1.00 to 1.20) in women versus HR of 1.32 (95% CI: 1.24 to 1.41) in men; and NT-proBNP HR of 1.54 (95% CI: 1.37 to 1.74) in women versus HR of 1.89 (95% CI: 1.75 to 2.05) in men. Population-attributable risk of all risk factors combined was 59.0% in women and 62.9% in men.. Women had a lower risk for HF than men. Sex differences were seen for systolic blood pressure, heart rate, CRP, and NT-proBNP, with a lower HF risk in women.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Blood Pressure; C-Reactive Protein; Cohort Studies; Europe; Female; Heart Failure; Heart Rate; Humans; Hypertension; Incidence; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Distribution; Sex Factors; Smoking; Stroke; Systole; Young Adult

Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure.. The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin.. Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

Topics: Animals; Atrial Function, Left; Atrial Natriuretic Factor; Benzhydryl Compounds; Diet, High-Fat; Disease Models, Animal; Fatty Acids; Fibrosis; Gene Expression Regulation; Glucosides; Heart Failure; Hemodynamics; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Rats, Inbred SHR; Rats, Inbred WKY; Recovery of Function; Sodium-Glucose Transporter 2 Inhibitors; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Ventricular Remodeling

Topics: Aged; Atrial Fibrillation; China; Chronic Disease; Cognitive Dysfunction; Coronary Artery Disease; Diabetes Mellitus; Female; Heart Failure; Hospitalization; Humans; Hypertension; India; Malaysia; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Singapore; Smoking; Stroke; Troponin T

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Female; Humans; Hypertension; Japan; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; ROC Curve; Troponin T

Isolated systolic hypertension (ISH) and elevated pulse pressure (PP) are common blood pressure (BP) abnormalities in older adults, reflect poor vascular compliance, and can signify risk for cardiovascular outcomes. We sought to characterize the associations of ISH and widened PP with high-sensitivity Troponin-T (hs-cTnT; a marker of myocardial damage) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; a marker of hemodynamic stress) levels in older adults. We performed a cross-sectional analysis of 5,251 Atherosclerosis Risk in Communities (ARIC) study participants without heart failure who attended visit 5 (2011 to 2013). We used logistic regression to evaluate the association of ISH (systolic BP ≥140 mm Hg and diastolic BP < 90 mm Hg) and quartiles of PP with detectable (≥5 ng/L) and elevated hs-cTnT (≥14 ng/L); as well as elevated NT-proBNP (≥100 pg/mL). The mean age was 75 years, 58% were women, and 78% were white. ISH was present in 24.7% and PP ≥ 70 mm Hg in 30.3% of this cohort. Compared to participants with nonhypertensive BP (<140/90 mm Hg), ISH was independently associated with hs-cTnT and NT-proBNP; adjusted odds ratio of 1.5 (95% confidence interval: 1.1 to 1.9) for detectable hs-cTnT; 1.3 (1.1 to 1.5) for elevated hs-cTnT; and 1.8 (1.6 to 2.1) for elevated NT-proBNP. Increasing quartiles of PP were also significantly associated with both elevated hs-cTnT (p-for-trend <0.0001) and NT-proBNP (p-for-trend <0.0001). These associations were not modified by BP treatment status. In conclusion, ISH and wide PP are relatively common in older adults despite contemporary BP treatment and are associated with abnormalities in hs-cTnT and NT-pro BNP, findings that could guide personalized treatment of older patients with these BP aberrations.

Topics: Atherosclerosis; Biomarkers; Blood Pressure; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Risk Assessment; Risk Factors; Systole; Troponin T; United States

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Cholesterol; Cystatin C; Diabetes Mellitus; Female; Glycopeptides; Humans; Hypertension; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Prospective Studies; Protein Precursors; Risk Factors; Sex Factors; Smoking; Sweden

Human serum albumin (HSA) is the most abundant circulating protein in the body and presents an extensive range of biological functions. As such, it is prone to undergo post-translational modifications (PTMs). The non-enzymatic early glycation of HSA, one of the several PTMs undergone by HSA, arises from the addition of reducing sugars to amine group residues, thus modifying the structure of HSA. These changes may affect HSA functions impairing its biological activity, finally leading to cell damage. The aim of this study was to quantitate glycated-HSA (GA) levels in the plasma of heart failure (HF) patients and to evaluate the biological effects of GA on HL-1 cardiomyocytes. Plasma GA content from HF patients and healthy subjects was measured by direct infusion electrospray ionization mass spectrometry (ESI-MS). Results pointed out a significant increase of GA in HF patients with respect to the control group (p < 0.05). Additionally, after stimulation with GA, proteomic analysis of HL-1 secreted proteins showed the modulation of several proteins involved, among other processes, in the response to stress. Further, stimulated cells showed a rapid increase in ROS generation, higher mRNA levels of the inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and higher levels of the oxidative 4-HNE-protein adducts and carbonylated proteins. Our findings show that plasma GA is increased in HF patients. Further, GA exerts pro-inflammatory and pro-oxidant effects on cardiomyocytes, which suggest a causal role in the etiopathogenesis of HF.

Topics: Aged; Case-Control Studies; Cell Death; Cell Line; Dyslipidemias; Female; Gene Expression Profiling; Gene Ontology; Glycated Serum Albumin; Glycation End Products, Advanced; Glycosylation; Heart Failure; HSP90 Heat-Shock Proteins; Humans; Hypertension; Interleukin-6; Lysine; Male; Middle Aged; Molecular Sequence Annotation; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Carbonylation; Protein Processing, Post-Translational; Reactive Oxygen Species; Serum Albumin; Serum Albumin, Human; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Blood Pressure; Cardiology; Coronary Artery Disease; Drug-Eluting Stents; Dyslipidemias; Electrocardiography; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nuclear Medicine; Ventricular Dysfunction, Left

The aim of the present study was to establish a convenient clinically applicable assay method for chymase-dependent angiotensin II forming activity of circulating mononuclear leukocytes (CML), which was potentially a marker of tissue chymase activity. Using this method, association between CML chymase activity and clinical parameters was determined. Cardiovascular outpatients (n = 170) without taking antihypertensive medication were recruited. An ELISA for chymase-dependent angiotensin II-forming activity in CML was established using Nma /Dnp-modified angiotensin I. Logistic regression analysis revealed that age and male gender were significant independent determinants of the increased CML chymase activity. After adjustment by age and gender, the CML chymase activity was positively correlated with systolic blood pressure, pulse rate, and the brain natriuretic peptide level. The relation between blood pressure and CML chymase activity suggests that it might reflect that increased tissue chymase activity contributes to systemic high blood pressure and heart rate because plasma chymase is inactive due to inhibitory plasma inhibitors.

Topics: Adult; Age Factors; Aged; Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Chymases; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Heart Rate; Humans; Hypertension; Leukocytes, Mononuclear; Male; Middle Aged; Natriuretic Peptide, Brain; Sex Factors

The prevalence and morbidity of hypertension continues to grow globally and improved methods of stratifying risk and identifying organ damage earlier are required. Methods such as echocardiography and population-based risk scores are suggested by guidelines as approaches to aid in risk stratification. However, biomarkers such as natriuretic peptides may help provide such an approach.. We analyzed data from the screening to prevent heart failure cohort including participants with hypertension with and without a history of a cardiovascular (CV) event at baseline. We investigated the ability of ventricular dysfunction on echocardiography at baseline and of B-type natriuretic peptide (BNP) levels in predicting future major adverse CV events (MACE) and death. We also investigated the use of Systematic COronary Risk Evaluation (SCORE) to predict these events in the uncomplicated cohort.. In total, 572 patients (427 with uncomplicated hypertension) were included. Thirty-three patients had MACE or died during follow up. In a univariate analysis, BNP was predictive of MACE and death in all groups. Ventricular dysfunction was not predictive of MACE and death in any group. Both BNP and SCORE had predictive value in this category. However, the magnitude and strength of the continuous association between BNP and events is higher and BNP adds significantly to the predictive value of SCORE as determined by likelihood ratios. The net reclassification improvement for BNP compared to stage B heart failure was 0.20.. This study demonstrates that in patients with hypertension, BNP is superior to ventricular dysfunction on echocardiography in the prediction of risk of MACE and death in a community-based cohort of patients with complicated and uncomplicated hypertension.

Topics: Aged; Biomarkers; Blood Pressure; Disease Progression; Echocardiography; Female; Humans; Hypertension; Ireland; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Recent studies have suggested that the natriuretic peptide system may be endogenously suppressed in black individuals who are free of prevalent cardiovascular disease. Whether natriuretic peptide levels contribute to racial disparities in clinical outcomes is unknown.. To examine racial differences in N-terminal pro-B-type natriuretic peptide (NTproBNP) levels and their association with all-cause mortality and cause-specific mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.. Baseline NTproBNP levels were measured in a randomly selected sample of 4415 REGARDS study participants. Those with prevalent cardiovascular disease and renal dysfunction were excluded. From July 1, 2003, to September 12, 2007, among the remaining 1998 individuals, racial differences in NTproBNP levels were estimated, and the percentage difference in NTproBNP levels by race was meta-analyzed and compared with published results on participants free of prevalent cardiovascular disease from the Dallas Heart Study and Atherosclerosis Risk in Communities study, using random effects modeling. The association of NTproBNP levels, race, all-cause mortality, and cause-specific mortality in the REGARDS study was studied using appropriate modeling techniques. Data analysis was conducted from July 1, 2003, to March 31, 2016.. Racial differences in NTproBNP levels and association with all-cause mortality and cause-specific mortality.. Among the 1998 participants studied (972 women and 1026 men; median age, 63 years [interquartile range, 54-72 years]), median NTproBNP levels in black individuals were significantly lower than those in white individuals (46 pg/mL [interquartile range, 23-91] vs 60 pg/mL [interquartile range, 33-106]; P < .001). With multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals (β, -0.32; 95% CI, -0.40 to -0.24; P < .001) in the REGARDS study. In meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals. Among the REGARDS study participants, for every 1-SD higher log NTproBNP, there was a 31% increased risk of death in the multivariable-adjusted model (hazard ratio, 1.31; 95% CI, 1.11-1.54). This increase was driven primarily by association of NTproBNP with cardiovascular mortality (hazard ratio, 1.69; 95% CI, 1.19-2.41). No interaction between race and NTproBNP levels was observed with all-cause mortality and cause-specific mortality.. Plasma NTproBNP levels are significantly lower in black individuals as compared with white individuals in the REGARDS study and in pooled results from the REGARDS study, Dallas Heart Study, and Atherosclerosis Risk in Communities study. Higher NTproBNP levels were associated with higher incidence of all-cause mortality and cardiovascular mortality in healthy black and white individuals, and this association did not differ by race.

Topics: Aged; Black or African American; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Residence Characteristics; Stroke; United States; White People

Topics: Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Registries; Risk Factors; Sodium

Topics: Angiotensin II; Animals; Antihypertensive Agents; Apoptosis; Atrial Natriuretic Factor; bcl-2-Associated X Protein; Blood Pressure; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiotonic Agents; Caspase 3; Cell Line; Gallic Acid; Gene Expression Regulation; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Nitric Oxide Synthase; p300-CBP Transcription Factors; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Tumor Suppressor Protein p53

Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown.. In a knockout mouse model of TN-C, we investigated the effect of 10 weeks of pressure overload using transverse aortic constriction (TAC). Cardiac function was determined by magnetic resonance imaging. The expression of MMP-2 and MMP-9, CD147 as well as myocardial fibrosis were assessed by immunohistochemistry. The expression of TN-C was assessed by RT-qPCR and ELISA. TN-C knockout mice showed marked reduction in fibrosis (P < 0.001) and individual cardiomyocytes size (P < 0.01), in expression of MMP-2 (P < 0.05) and MMP-9 (P < 0.001) as well as preserved cardiac function (P < 0.01) in comparison with wild-type mice after 10 weeks of TAC. In addition, CD147 expression was markedly increased under pressure overload (P < 0.01), irrespectively of genotype. TN-C significantly increased the expression of the markers of hypertrophy such as ANP and BNP as well as MMP-2 in H9c2 cells (P < 0.05, respectively).. Our results are pointed toward a novel signaling mechanism that contributes to LV remodeling via MMPs upregulation, cardiomyocyte hypertrophy as well as myocardial fibrosis by TN-C under chronic pressure overload.

Topics: Animals; Basigin; Cardiac Output; Cell Line; Fibrosis; Genotype; Hypertension; Hypertrophy, Left Ventricular; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Signal Transduction; Tenascin; Ventricular Remodeling

Optimal blood pressure for prevention of cardiovascular (CV) events in patients with Type 2 diabetes mellitus (T2DM) remains uncertain and there is concern for increased risk with low diastolic blood pressure (DBP). This study analysed the association between blood pressure and CV outcomes in high-risk patients with T2DM.. Patients with T2DM and elevated CV risk were enrolled in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis in Myocardial Infarction 53 trial. Cardiovascular outcomes were compared in the biomarker subgroup (n = 12 175) after stratification by baseline systolic blood pressure (SBP) and DBP. Adjusted risk was calculated by blood pressure stratum using clinical covariates plus N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT). Trends were tested using linear and quadratic models. Adjusted risk of the composite endpoint of CV death, myocardial infarction (MI), or ischaemic stroke showed U-shaped relationships with baseline SBP and DBP (Pquadratic ≤ 0.01) with nadirs at SBP 130-140 or DBP 80-90 mmHg. Diastolic blood pressure <60 mmHg was associated with increased risk of MI (adjusted hazard ratio 2.30; 95% confidence interval 1.50-3.53) relative to DBP 80-90 mmHg. Adjusted odds of hsTnT concentration ≥14 ng/L showed U-shaped relationships with SBP and DBP (Pquadratic ≤ 0.01). The relationships between low DBP, elevated hsTnT, and increased MI remained after exclusion of patients with prior heart failure or NT-proBNP >median, suggesting that the relationship was not due to confounding from diagnosed or undiagnosed heart failure.. In patients with diabetes and elevated CV risk, even after extensive adjustment for underlying disease burden, there was a persistent association for low DBP with subclinical myocardial injury and risk of MI.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diastole; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Care Planning; Peptide Fragments; Stroke; Systole; Troponin T

Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy.. The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPβ, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis.. At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn't statistically significant difference between the SHR and intervention groups. Staining with Masson's trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPβ expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks.. This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPβ/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy.

Topics: Animals; Apoptosis; Atorvastatin; Atrial Natriuretic Factor; Blood Pressure; CCAAT-Enhancer-Binding Protein-beta; Echocardiography; Hypertension; Hypertrophy; Male; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Uncoupling Protein 3; Up-Regulation; Ventricular Remodeling

Analyzing the relationships between biomarkers representing distinct pathophysiologic pathways and microalbuminuria (MA) can strengthen the identifying ability for renal damage and illuminate previously unrecognized pathways for the pathogenesis of renal damage. The current analysis was to clarify the associations between biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), homocysteine and uric acid (UA), and MA in Chinese middle-aged and elderly from communities.. All 839 residents had complete set of these biomarkers and full assessment of MA.. Prevalence of participants with MA was 13.5% (113 participants). Levels of age, systolic blood pressure (SBP), fasting blood glucose (FBG), homocysteine and NT-proBNP and proportion of cigarette smoking in participants with MA significantly exceeded those in participants without MA (p < 0.05 for all). In single-marker and multi-marker models of linear and logistic regression analyses, homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) were statistically significant in relation to MA. Additionally, no matter which biomarker was directed at, levels of age, SBP and FBG and proportion of cigarette smoking had significant associations with MA. Homocysteine and NT-proBNP levels (p < 0.05 for all) rather than hsCRP and UA levels (p > 0.05 for all) had significant abilities to identify MA.. Both single-marker and multi-marker analyses confirmed that homocysteine and NT-proBNP were associated with MA in Chinese middle-aged and elderly from communities after adjustment for multiple confounders.

Topics: Aged; Aged, 80 and over; Albuminuria; Biomarkers; C-Reactive Protein; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Smoking; Uric Acid

Acute heart failure (AHF) is one of the most commonly seen clinical cases, with a high rate of re-hospitalization and mortality. AHF can be divided into two categories based on the systolic function of the left ventricle, which are heart failure with reduced ejection fraction (HFREF) and heart failure with preserved ejection fraction (HFPEF). Pathogenesis and treatment of the two are quite different. In this article we attempted to explore the value of combined use of clinical and laboratory indicators in the differential diagnosis of AHFREF and AHFPEF.. AHF patients ≥18 years old without valvular heart disease, acute myocardial infarction, renal dysfunction, ongoing hemodialysis or acute pulmonary embolism were chosen. Patients with left ventricular ejection fraction (LVEF) <0.5 fell into AHFREF group, and the remaining were placed in the AHFPEF group. Binary logistic regression analysis of age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), NT-proBNP, blood glucose, LVEF and cardiothoracic ratio (CTR) as covariates and AHF types as dependent variables.. 166 patients were enrolled and, among them, 66 cases (39.8%) were in the AHFREF group and 100 cases (60.2%) in the AHFPEF group. We chose age, SBP, DBP, HR and NT-pro BNP as covariates in the binary logistic regression analysis, and obtained the regression equation and the results were statistically significant (χ2=32.177, p<0.001). Hosmer-Lemeshow model test was (χ2=8.654, p=0.372). Samples were tested with the remaining approximately 30% of the subjects.. Combined application of clinical and laboratory indicators, such as age, blood pressure, HR and NT-proBNP play an important role in the differential diagnosis of AHFREF and AHFPEF.

Topics: Aged; Area Under Curve; Blood Glucose; Blood Pressure; Female; Heart Failure; Heart Rate; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ventricular Function, Left

Topics: Aortic Aneurysm; Aortic Dissection; Aortic Valve Insufficiency; Biomarkers; Blood Vessel Prosthesis Implantation; Dyspnea; Heart Failure, Diastolic; Heart Murmurs; Heart Valve Prosthesis Implantation; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Elevated plasma concentration of retinol-binding protein 4 (RBP4) has recently emerged as a potential new risk factor for cardiovascular diseases, including hypertension (HT) and coronary artery disease (CAD). Limited data suggest that RBP4 promotes inflammatory damage to cardiomyocytes and participates in the development of heart failure (HF). This study aimed to analyze the relationship between concentrations of plasma RBP4 and serum N-terminal proBNP (NT-proBNP), a powerful biomarker of left ventricle dysfunction, in the older Polish population.. The study sample consisted of 2,826 (1,487 men) participants of the PolSenior study, aged 65 years and older, including a subgroup hospitalized for HF (n = 282). In all subjects, plasma concentrations of RBP4, interleukin-6 (IL-6), serum level of NT-proBNP, and hs-CRP were measured. Additionally, BMI, estimated glomerular filtration rate (eGFR), and HOMA-IR were calculated. The prevalence of HT, CAD, atrial fibrillation (AF), and medication were considered as potential confounders.. Similar RBP4 levels were found in subjects with NT-proBNP < 125 and ≥125 ng/mL, with and without AF, and in the subgroups hospitalized for HF with and without AF. Regression analysis revealed no association between log10(NT-proBNP) and log10(RBP4). Plasma levels of RBP4 were increased by HT occurrence and diuretic therapy, while diminished with regard to female gender, age, eGFR values, AF, and IL-6 levels.. Our results show that RBP4 is affected by GFR but cannot be considered as an independent biomarker of heart muscle dysfunction.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Confounding Factors, Epidemiologic; Coronary Artery Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Retinol-Binding Proteins, Plasma; Ventricular Dysfunction, Left

Heart rate (HR) assessed by electrocardiogram (ECG-HR) and pulse rate (PR) measured in a physician's office (office-PR) are taken with subjects in different body positions-i.e., supine vs. sitting. Although analysis of HR differences according to body position could provide new practical insights, there have been few studies on the subject. We herein investigated whether the difference between office-PR and ECG-HR (delta HR) was associated with brain natriuretic peptide (BNP) levels and left ventricular mass (LVM).. Among the 4,310 patients with 1 or more cardiovascular risk factors recruited for the Japan Morning Surge-Home Blood Pressure study, we excluded those with atrial fibrillation or a prescribed β-blocker. We analyzed the 2,972 patients who had ECG-HR, office-PR, and BNP data and 1,061 patients with echocardiography data.. In the complete patient series, office-PR was significantly higher than ECG-HR (72.1 ± 10.3 vs. 66.6 ± 11.9 bpm, P < 0.001). When we divided patients into quintiles based on the delta HR, the BNP level and LVM index (LVMI) decreased across categories after adjustment for traditional cardiovascular risk factors (each P ≤ 0.001). In a multiple linear regression analysis, the delta HR was independently and significantly associated with both the log-transformed BNP level (β = -0.179, P < 0.001) and LVMI (β = -0.113, P = 0.001) adjusted for covariates.. A decreased delta HR was positively associated with the BNP level and LVMI. Without the requirement of a special technique, this evaluation might indicate potential cardiac overload and provide a clinical sign related to heart failure.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Disease Progression; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Office Visits; Predictive Value of Tests

Pulse pressure (PP) is a risk factor for cardiovascular diseases and is associated with increased afterload and myocardial oxygen demand. Brain natriuretic peptide (BNP) and heart-type fatty acid-binding protein (H-FABP) are known as biomarkers indicating ventricular wall stress and silent myocardial damage. However, the association between PP and ventricular wall stress and silent myocardial damage in the general population is unclear. The authors enrolled 3504 patients who participated in a community-based annual health check. Serum levels of BNP and H-FABP were measured as markers of ventricular wall stress and silent myocardial damage. Patients were divided into four groups according to the quartiles of PP. Patients in the highest PP group showed higher serum BNP and H-FABP levels than that of the other groups. Multivariate logistic analysis showed that high PP was independently associated with ventricular wall stress and silent myocardial damage on the basis of BNP and H-FABP levels. Compared with systolic blood pressure, diastolic blood pressure, and mean blood pressure, PP was superior in predicting ventricular wall stress and silent myocardial damage evaluated according to BNP and H-FABP levels, which was reflected by the receiver operating characteristic analysis. Screening of healthy patients revealed that high PP was related to high BNP and H-FABP levels, suggesting that an asymptomatic general population with high PP may be exposed to ventricular wall stress and myocardial damage and might be susceptible to silent heart failure.

Topics: Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Fatty Acid Binding Protein 3; Female; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; ROC Curve

Plasma brain natriuretic peptide (BNP), a diagnostic marker of cardiovascular diseases, has been previously linked to cerebrovascular diseases. Our goal was to determine whether plasma BNP level is helpful for identifying high-risk individuals who are likely to present with the 3 main subtypes of cerebral small vessel diseases (CSVDs), namely, white matter lesions, lacunar infarcts, and cerebral microbleeds, on magnetic resonance imaging (MRI) in patients with hypertension.Three hundred forty-six consecutive hypertensive patients presenting at our cardiology or neurology clinic were investigated. Plasma BNP level was measured by chemiluminescent microparticle immunoassay. The presence of CSVD was assessed by 1.5-T brain MRI. Multivariate linear regression was used to determine whether individual or combined MRI-defined CSVD subtypes were associated with BNP level, after adjustment for several covariates.The mean age of patients was 69.1 ± 9.8 years, and 44.2% were female. The highest quartile BNP group was positively associated with advanced age, female sex, clinically manifesting cardiac diseases, and ischemic CSVD (white matter lesions and lacunar infarcts) and no association with cerebral microbleeds. According to multivariate linear regression, white matter lesions [β = 0.722; 95% confidence interval (95% CI), 0.624-0.819] and lacunar infarcts (β = 0.635; 95% CI, 0.508-0.762) were independently associated with BNP level, even after controlling for vascular risk factors and clinically manifesting cardiac diseases. Combined white matter lesions and lacunar infarcts were more strongly associated with BNP level than each subtype alone. With the cutoff value of 106.4 pg/mL, BNP level had a sensitivity, a specificity, and an area under the curve of 95.2%, 64.9%, and 0.799, respectively, for white matter lesions, whereas the values were 143.0 pg/mL, 81.6%, 73.5%, and 0.848, respectively, for lacunar infarcts.Plasma BNP level, which is independently correlated with individual or combined white matter lesions and lacunar infarcts, is a useful molecular marker for identifying ischemic CSVD in patients with hypertension.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Cerebral Small Vessel Diseases; Female; Humans; Hypertension; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sex Factors; Stroke, Lacunar

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHR-TMAO group had lower plasma NH

Topics: Animals; Antihypertensive Agents; Blood Pressure; Fibrosis; Hypertension; Male; Methylamines; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Wistar; Vasopressins

Objective The management of blood pressure (BP) in hypertensive patients is the key to preventing a progression of organ damage. The brachial BP (bBP) has been used as the representative method for measuring the BP. The central BP (cBP), which is, different from the bBP due to the propagation and the reflection of the pulse wave in the arterial system, has recently received attention because it can now be estimated non-invasively. We examined the relationships between the difference in the central systolic BP (csBP) and the brachial systolic BP (bsBP) (Δ) and other factors in hypertensive patients. Methods The bsBP and csBP were measured in patients with essential hypertension and the relationships between the bsBP, csBP, or Δ and background factors including age, the brain natriuretic peptide (BNP) level, the estimated glomerular filtration rate (eGFR), flow-mediated vasodilation (an index of vascular endothelial function), the cardio-ankle vascular index (CAVI, an index of arteriosclerosis), and the carotid intima-media thickness (an index of atherosis) were investigated. Results The data of 191 patients were analyzed. Although there was no significant correlation between the CAVI and the bsBP; positive correlations were observed between the CAVI and the csBP (r=0.249, p=0.001). The Δ value showed significant positive correlations with age, and the BNP, eGFR, and CAVI values. Conclusion The csBP is more strongly associated with arteriosclerosis than the bsBP. Moreover, the Δ value is more strongly associated with cardiac function, renal function, and arteriosclerosis than the bsBP or csBP. These data suggested that the Δ value may have a greater prognostic value than the bsBP or csBP and may be worth calculating in the clinical setting.

Topics: Adult; Age Factors; Aged; Ankle Brachial Index; Arteriosclerosis; Blood Pressure; Blood Pressure Determination; Carotid Intima-Media Thickness; Essential Hypertension; Female; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Vasodilation

Elevated B-type natriuretic peptide (BNP) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the BNP gene (. A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45-64 years; 1987-1989), with follow-up visits occurring every 3 years (visit 2-visit 4, 1990-1999), followed by visit 5 (2011-2013). NT-proBNP levels were measured at visits 2, 4, and 5. At visit 2, the GG genotype (frequency 18%) was associated with a 41% higher mean plasma level of NT-proBNP compared with the AA genotype (frequency 34%), with intermediate values observed in AGs (. The rs198389 G allele in the

Topics: Black or African American; Blood Pressure; Chi-Square Distribution; Female; Genetic Predisposition to Disease; Humans; Hypertension; Kaplan-Meier Estimate; Linear Models; Longevity; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Phenotype; Polymorphism, Single Nucleotide; Predictive Value of Tests; Promoter Regions, Genetic; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; United States; Up-Regulation; White People

Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD. Sustained BNP production significantly reduced kidney weight, renal cystic indexes and fibrosis, in concert with suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic epithelial cell proliferation, suppressed fibrotic gene expression, and increased intracellular calcium. Together, our data demonstrate multifaceted effects of sustained activation of guanylyl cyclase A on polycystic kidney and liver disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel therapeutic strategy for hepatorenal fibrocystic diseases.

Topics: Animals; Cell Proliferation; Cyclic AMP; Cyclic GMP; Cysts; Disease Models, Animal; Disease Progression; Epithelial Cells; Female; Fibrosis; Genetic Vectors; Humans; Hypertension; Kidney; Liver; Liver Diseases; Male; Natriuretic Peptide, Brain; Parvovirinae; Polycystic Kidney, Autosomal Recessive; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Signal Transduction; Vasopressins

Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin-twin transfusion syndrome recipient's vascular architecture remains unknown.. We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age-matched controls; and (3) test the association of artery vein angle with recipient heart failure.. We compared 3 groups prospectively: twin-twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3-dimensional color-Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin-twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle.. Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long-term implications.

Topics: Adult; Amniotic Fluid; Female; Fetofetal Transfusion; Gestational Age; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Pregnancy; Prospective Studies; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal; Umbilical Arteries

The optimal therapy in patients with heart failure preserved ejection fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB), a major anti-hypertensive drugs in Japan, is also recommend as class IIa in patients with HFpEF. However, the difference between azelnidipine, an L type CCB, and cilnidipine, an N type CCB, is unclear. We investigated the difference between azelnidipine and cilnidipine in patients with HFpEF and HT.. Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013 to March 2015 were enrolled. Initially, cilnidipine was used, and then switched to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests, echocardiography, and cardiac-scintigraphy (. There was no statistically significant difference in BP. B type natriuretic peptides were significantly reduced (pre-state: 195.4 ± 209.7 pg/ml and post-state: 140.7 ± 136.4 pg/ml, p = 0.050). In echocardiography, the TEI index tended to be decreased (pre-state: 0.47 ± 0.15 and post-state: 0.42 ± 0.08, p = 0.057). As for MIBG, there was no significant change in the heart/mediastinum ratio. However, the washout rate was significantly reduced (pre-state: 44.7 ± 12.2 and post-state: 40.7 ± 12.1, p = 0.011). In addition, there was no statistically significant change, although HR tended to decrease by switching to azelnidipine (pre-state: 62.7 ± 11.6 and post-state: 61.8 ± 16.5, p = 0.373).. In patients with HT and HFpEF, azelnidipine improved the severity of HF and cardiac sympathetic nerve activity compared with cilnidipine.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Echocardiography; Female; Heart Failure; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Radionuclide Imaging; Renin-Angiotensin System; Stroke Volume

Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases.. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus.. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects.. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

Topics: Aged; Albuminuria; Biomarkers; Blood Pressure; Coronary Disease; Diabetes Mellitus; Female; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Stiffness

Natriuretic peptides (NP), ANP and BNP, are produced by cardiomyocytes when there is stretching of the ventricular and auricular walls in heart failure (HF). Their vasodilatator and natriuretic effect oppose to volume and pressure overload occurring in HF. Several studies have observed decreased levels of NP in obese and diabetic people and in patients with insulin resistance. This decrease could contribute to hypertension, frequently observed in obesity. NP have also a lipolytic action. Low levels of NP could promote obesity. Therefore in obese patients normal BNP levels cannot a priori exclude HF. Normal values must be adjusted according to obesity degree and heart failure stage.. Les peptides natriurétiques (PN) ANP

Topics: Diabetes Mellitus; Heart Failure; Humans; Hypertension; Insulin Resistance; Natriuretic Peptide, Brain; Obesity

Elevated B-type natriuretic peptide (BNP) is a hallmark in heart failure (HF). Diabetic patients with chronic HF seem to have higher BNP than nondiabetics. We studied, in acute HF, if BNP levels are different between diabetics and nondiabetics.. From a prospectively recruited population of acute HF patients, we selected a convenience sample. In pair-matched analysis, each diabetic patient was matched with a nondiabetic of the same age (±1 year), gender, and according to left ventricular systolic dysfunction. Diabetics and nondiabetics were compared. Cox-regression analysis was used to analyse the prognostic impact of diabetes.. We studied 328 patients, mean age: 78 years, 44.5% male. Diabetics were more often hypertensive and had ischemic HF; they had higher body mass index, lower haemoglobin, and worse renal function. Diabetics were more often discharged on ACE inhibitors/ARB, antiplatelet therapy, and statins. Neither admission nor discharge BNP values differed between diabetics and pair-matched nondiabetics. One-year mortality was also nondifferent between pairs of diabetics and nondiabetics: 44 (26.8%) and 46 (28.0%), respectively. HR for 1-year mortality in diabetics was 1.00 (95% CI: 0.82-1.24) compared with nondiabetics.. HF patients with diabetes have similar neurohumoral activation when compared with nondiabetics. One-year mortality is also nondifferent after matching for age, gender, and systolic function.

Topics: Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Prognosis

The volume state of dialysis patients is important in guiding the dialysis process. Volume overload in these patients is associated with inflammation. The objectives of the present study were to assess the body composition of patients on hemodialysis; to determine the concentrations of B-type natriuretic peptide (BNP) in plasma and evaluate the association of BNP concentrations with volume overload; to determine the concentrations of C-reactive protein (CRP), albumin and superoxide dismutase (SOD) activities as indicators of inflammatory or antioxidant processes. The study included 79 maintenance hemodialysis patients. Assessment of body compartments was carried out using a body composition monitor (BCM). After BCM measurements, blood samples were taken from the patients for laboratory tests. There were 40 (50.6%) volume-overloaded patients (relative overhydration >15%). These patients had a higher prevalence of arterial hypertension (P < 0.05), significantly higher concentrations of BNP (P = 0.01), lower body mass index (P < 0.05) and lower fat tissue index (P < 0.05). There was a positive correlation between plasma BNP and CRP concentrations (ρ = 0.231; P < 0.05), and a negative correlation between (log) BNP and albumin (r = -0.021; P < 0.05), as well as (log) CRP and albumin concentrations (r = -3; P < 0.01). SOD activity was positively correlated with albumin concentrations (r = 0.254; P < 0.05). The concentrations of BNP in this study were associated with volume overload and inflammatory markers. Patients with a higher albumin concentration had higher SOD activity.

Topics: Aged; Albumins; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Renal Insufficiency, Chronic; Superoxide Dismutase

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Proteins; Cross-Sectional Studies; Female; Galectin 3; Galectins; Heart Failure; Hospitalization; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Prognosis; Stroke Volume

Volume overload, frequently clinically asymptomatic is considered as a causative factor limiting the effectiveness of antihypertensive therapy in haemodialysis (HD) patients. Therefore, the aim of this study was to assess plasma levels of N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) and a C-terminal portion of the precursor of vasopressin (CT-proAVP, copeptin), surrogate markers of volume overload in HD patients in relation to the number of antihypertensive drugs used in the hypertension treatment.. One hundred and fifty adult HD patients (92 males) were enrolled into this study. Clinical data concerning blood pressure (BP) measurements prior haemodialysis session and pharmacotherapy were collected from all patients. In addition to routine laboratory parameters, plasma levels of NT-proBNP and CT-proAVP were measured, and daily sodium and water consumption were estimated with a portion-size food frequency questionnaire.. Among 145 (96.7%) hypertensive HD patients, 131 were receiving antihypertensive medication. Despite antihypertensive therapy, 31.0% had inadequate BP control. Plasma concentration of NT-proBNP was associated with systolic (R=0.19; p=0.02) but not diastolic BP values and with the number of received antihypertensive drugs (R=0.21; p=0.01). The highest NT-proBNP values were observed in patients receiving 3 or more antihypertensive drugs. In contrast, no significant correlation was found between plasma CT-proAVP concentrations and BP values as well as and the number of antihypertensive drugs. Receiver operator curve analysis showed that NT-proBNP values over 13,184 pg/mL predicted the use of at least 3 antihypertensive drugs in maximal doses in the therapy of hypertension, similar analyses performed for CT-proAVP showed much less specificity.. 1. Increased levels of NT-proBNP seems to be a better biomarker of multidrug antihypertensive therapy requirement than CT-proAVP. 2. Whether estimation of NT-proBNP in these patients will be also better biomarker than copeptin in the prediction of cardiovascular complications related to hypertension needs further investigations.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Cardiovascular Diseases; Female; Glycopeptides; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic

Topics: Atrial Natriuretic Factor; Blood Pressure; Genome-Wide Association Study; Humans; Hypertension; Natriuretic Peptide, Brain

To identify the most significant factor influencing blood levels of cytokines in patients at high and very high cardiovascular risk.. A patient base from the "Management of chronic patients with multiple diseases" project was analyzed. 523 patients (mean age, 87±17.8) were included. Plasma samples were analyzed for concentrations of sodium, creatinine, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, and NT-proBNP. GFR was calculated using the CKD-EPI formula. Time-related CHF progression was assessed in one year; the time-related progression was considered an increase in CHF stage. Salt consumption was determined using the Charlton: SaltScreener questionnaire at the baseline visit and at one year. Low-salt diet containing 5 g of salt per day was recommended to all patients; 3.5 g of salt per day was recommended to patients with a documented diagnosis of CHF. Statistical analysis was performed using the Statistica 10.0 software.. 52.2 % of included patients consumed 6-10 g of salt per day; 43.4 % of patients consumed 10 g of salt or more per day; and only 4.4 % of patients consumed 5 g of salt or less per day. 21 % of included patients were at high risk of cardiovascular complications whereas for the vast majority of patients (79 %), the risk was stratified as very high. Two clusters of patients were formed based on the grade of hypertension, one-year CHF progression, and plasma levels of IL-6, -8, and -18. The one-year progression of CHF most significantly influenced the levels of IL-18, -8, and -6. The IL-6 level was correlated with the NT-proBNP level; an approximately similar degree of correlation was found for NT-proBNP and BP.. Therefore, the performed statistical analysis determined correlations between the following factors: IL-6 level, NTproBNP level, and one-year CHF progression.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Creatinine; Heart Failure; Humans; Hypertension; Interleukins; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Factors

Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Blood Pressure; Carotid Intima-Media Thickness; Echocardiography; Female; Glomerular Filtration Rate; Humans; Hypertension; Japan; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Renal Insufficiency, Chronic; Renin; Renin-Angiotensin System; Sodium, Dietary

Excess pressure integral (XSPI) derived from reservoir-excess pressure analysis is proposed as a novel indicator of cardiovascular dysfunction in hypertensives. Our study investigated the prognostic value of XSPI for stable heart failure (HF) patients.. In total, 238 subjects (mean age 63 ± 18 years, 111 male), comprising 168 stable HF patients with either reduced (SHF; n = 64) left ventricular (LV) ejection fraction (EF) or isolated diastolic dysfunction (DHF, n = 104), and 70 healthy controls, were enrolled. Tonometry-derived carotid pressure waveforms were analyzed with the reservoir pressure theory. XSPI was calculated by subtracting the reservoir pressure from carotid pressure waveform.. XSPI in SHF and DHF (14.01 ± 5.16 and 13.90 ± 5.05 mm Hg•s) were significantly higher than that in controls (11.01 ± 3.67 mm Hg•s, both P < 0.001). During a median follow-up of 9.9 years, 56 deaths occurred. XSPI was a significant independent predictor of total mortality after adjusting for age, sex, left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (hazard ratio = 4.37 per 1 SD, 95% confidence interval, 1.31-14.58). In subgroup analysis by different baseline characteristics including age, gender, NT-proBNP, LVEF, and GFR, higher XSPI was consistently associated with greater risk of total mortality.. In patients with stable HF, XSPI, a novel maker of cardiovascular dysfunction, was associated with long-term risk of total mortality.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Blood Pressure; Carotid Arteries; Female; Heart Failure; Humans; Hypertension; Male; Manometry; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Sex Factors; Stroke Volume; Taiwan; Wavelet Analysis

Background The aims of this study were (a) to test the ability of N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect subclinical target organ damage (TOD) denoted by left ventricular hypertrophy (LVH), aortic stiffness or renal damage and (b) to test its reproducibility in two different conditions in an ancillary study. Methods The study included 837 patients (50.9% men) with hypertension aged 50 ± 24 years with a median 24-h ambulatory blood pressure (BP) of 148/90 mmHg. LVH was assessed by transthoracic echocardiography and echocardiography, aortic stiffness was assessed by carotid-femoral pulse wave (PWV) measurements and renal dysfunction by measurements of the estimated glomerular filtration rate (eGFR) and microalbuminuria. Results After the exclusion of patients with a history of heart failure, NT-proBNP was independently correlated with sex, systolic BP, primary hypertension, PWV, LVH and eGFR, but not with microalbuminuria. The median (interquartile range) NT-proBNP increased gradually according to the number of target organs damaged: 42 (24-70), 77 (39-151), 141 (81-250) and 334 (177-556) pg/mL, for damage to 0, 1, 2 and 3 target organs, respectively ( p < 0.001). . For the same number of target organs damaged, NT-proBNP was higher in women and for secondary hypertension. A threshold at 90 pg/mL for men and 142 pg/mL in women had a specificity of 95% to detect at least one TOD (areas under ROC curve 0.790 and 0.783, respectively). The reproducibility of NT-proBNP was fairly good in this setting ( r = 0.952, p < 0.001, N = 325) Conclusion This study demonstrates that NT-proBNP mirrors the harmful effect of high BP on TOD. NT-proBNP could be used as an integrative tool for risk stratification in hypertension.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Blood Pressure Determination; Cohort Studies; Disease Progression; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Linear Models; Male; Middle Aged; Monitoring, Physiologic; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Retrospective Studies; Severity of Illness Index; Vascular Stiffness

Increased plasma retinol-binding protein 4 (RBP4), a novel adipokine, has been associated in previous studies with obesity, type 2 diabetes, dyslipidemia, hypertension (HT), atherosclerosis, and coronary artery disease. This study aimed to analyze the relationship between HT occurrence and its treatment, and plasma RBP4 concentrations in the older polish population. The study sample consisted of 1728 (890 men and 838 women) PolSenior study participants aged 65 years and older with available plasma samples and NT-proBNP values below 2000 pg/mL. The analysis included body mass index, waist circumference, blood pressure, antihypertensive medication, estimated glomerular filtration rate, serum glucose and insulin (and the homeostatic model assessment of insulin resistance), and plasma RBP4 levels. RBP4 plasma concentrations were higher in hypertensive (N = 645) than normotensive (N = 236) men (43.4 [30.4-64.8] vs. 38.1 [27.1-54.4] ng/mL, respectively; P < .01) but not in women (44.6 [29.6-63.5] vs. 40.7 [29.1-58.1] ng/mL, respectively; P = .21). In the subanalysis, higher plasma RBP4 levels were observed in women with treated than untreated HT and in subjects taking four of more antihypertensive drugs. The linear regression shown that estimated glomerular filtration rate (β = -0.015), thiazide diuretics (β = 0.041), and α-blockers (β = 0.049) were explaining log

Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Glucose; Blood Pressure Determination; Body Mass Index; Cohort Studies; Female; Geriatric Assessment; Glomerular Filtration Rate; Humans; Hypertension; Insulin; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Retinol-Binding Proteins, Plasma; Sex Factors; Waist Circumference

Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ≥ 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF <50%). Both hsTnI (p < 0.01) and NT-proBNP (p < 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (≥highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (≥highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p < 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p < 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p < 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could not predict future HF phenotypes.

Topics: Aged; Aged, 80 and over; Biomarkers; Echocardiography, Doppler; Female; Heart Failure; Hospitalization; Humans; Hypertension; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Stroke Volume; Troponin I; Ventricular Function, Left

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort.. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF.. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF.. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Topics: Adult; Age Factors; Albuminuria; Aminopeptidases; Antihypertensive Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Blood Glucose; Body Mass Index; C-Reactive Protein; Cohort Studies; Creatinine; Cystatin C; Female; Genetic Predisposition to Disease; Glomerular Filtration Rate; Heart Rate; Homeobox Protein PITX2; Homeodomain Proteins; Humans; Hypertension; Hypolipidemic Agents; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Phosphotransferases (Phosphate Group Acceptor); Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Small-Conductance Calcium-Activated Potassium Channels; Transcription Factors

Increasing age predicts ominous prognosis in heart failure. Age influences the success of therapeutic approaches and interacts with other prognostic predictors. We aimed to study the impact of age in long-term survival in different age strata.. Patients were prospectively included in an acute heart failure registry; those with acute coronary syndromes and those with primary valvular disease were excluded. Outcome studied was all-cause mortality. Follow-up was 5 years. A receiver-operating characteristic curve was used to define the age cut-off for 5-year death prediction. A multivariate Cox regression analysis was used to study mortality predictors. Analysis was stratified according to the 75-year-age cut-off.. We studied 473 patients. Mean age was 75 ± 12 years, 48.4% were men and 68.7% had reduced ejection fraction. Older patients were more often women, with preserved ejection fraction, history of arterial hypertension and atrial fibrillation; they were discharged in higher NYHA classes and with lower haemoglobin. Older patients were less often discharged with evidence-based heart failure therapy. In 5 years, 339 (71.7%) patients died. Patients aged more than 75 years had a multivariate-adjusted hazard ratio of mortality of 1.87 (95% confidence interval 1.46-2.38). In older patients, there was a 5% mortality increase per each 1-year increase in age; 75 years or less, age had no prognostic impact; and P for interaction (age continuous and age dichotomized) was 0.01.. Age is a strong long-term prognostic determinant in acute heart failure. The prognostic impact of age was significantly different between age subgroups: it was an independent predictor of mortality in patients aged more than 75 years and had no impact in those aged 75 years or less.

Topics: Acute Disease; Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Portugal; Prognosis; Prospective Studies; Registries; Risk Factors; ROC Curve; Survival Analysis; Ventricular Dysfunction, Left

Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress.. Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography).. At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls.. 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension.

Topics: Animals; Body Weight; Female; Fetal Nutrition Disorders; Hemodynamics; Hormones; Hypertension; Male; Mothers; Myocardium; Natriuretic Peptide, Brain; Organ Size; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Risk Factors; Sex Characteristics; Time Factors

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Catheter Ablation; Female; Heart Atria; Heart Diseases; Humans; Hypertension; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Veins; Tomography, X-Ray Computed; Troponin T; Vascular Remodeling

Augmented blood pressure (BP) variability over various time periods has been recognized as a risk factor for cardiovascular diseases. Both atrial and B-type natriuretic peptides (ANP and BNP) are secreted in response to volume or pressure overload to the heart, exerting natriuretic and vasodilator actions. In this study, we examined the relationships between year-by-year BP variability and plasma levels of ANP and BNP in the general population. Study subjects were local residents receiving an annual heath checkup, who had an estimated glomerular filtration rate of >30 ml min

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Female; Humans; Hypertension; Japan; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Risk Factors; Time Factors; Up-Regulation

Several registries have described patients hospitalized with heart failure (HF), but only few looked at outpatients in the ambulatory setting mostly without long-term follow-up. We sought to determine the clinical characteristics, management, and 1-year outcomes of patients with chronic HF in Saudi Arabia.. Part of a prospective multicenter nationwide registry; HEart function Assessment Registry Trial in Saudi Arabia (HEARTS) and included chronic HF patients referred to four HFCs between September 2009 and December 2011.. We enrolled 685 patients with mean age 55.66±15.97years, 70.1% were men and 96.1% were Saudis. The main etiologies of HF were CAD (38.8%), dilated cardiomyopathy (36.5%), and hypertension (10.5%). Severe left ventricular dysfunction was present in 70.6% and median NT-proBNP was 2934.37pg/ml. The prescription rates of evidence based therapies (EBTs) before admission to HFC, at discharge from 1st clinic visit, and at 1-year follow up were 90%, 91% and 94% for beta-blockers, 79%, 80%, and 86% for ACEi/ARBs and 44%, 45%, and 42% for aldosterone antagonists; respectively. ICD was inserted in 21.9% and CRT in 6.6% at enrollment and increased to 29.1% and 8.8% after one year respectively. The all-cause mortality rate at 1year was 9% and 93.7% of which was cardiac-related. The all-cause one-year hospitalization rate was 39% and the total emergency room visit rate was 50%.. Chronic HF patients in Saudi Arabia are younger, commonly have severe LV systolic dysfunction and have relatively high annual mortality and re-hospitalization rates.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Chronic Disease; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Natriuretic Peptide, Brain; Outcome and Process Assessment, Health Care; Peptide Fragments; Registries; Saudi Arabia; Severity of Illness Index; Symptom Assessment; Ventricular Dysfunction, Left

To determine the pathogenic role of insulin resistance in the formation of involutive sarcopenia and chronic heart failure (CHF) were examined 88 elderly patients with arterial hypertension (AH) and 32 elderly patients without cardiovascular disease by methods of carbohydrate metabolism and the level of brain natriuretic peptide precursor evaluation, muscle mass and strength measuring, echocardiography, 6 minute walking test. It was found that in the group of hypertensive patients with low mass and muscle strength significantly increased indices of insulin resistance and more expressed signs of the left ventricle myocardial dysfunction and functional class of heart failure, probably as a result of disorders of energy homeostasis, resulting from the deterioration of glucose into the muscle cells of the heart and skeletal muscles.. Для определения патогенетической роли инсулинорезистентности и инволютивной саркопении в формировании миокардиальной дисфункции и хронической сердечной недостаточности (ХСН) при старении обследованы 88 больных пожилого возраста c артериальной гипертензией (АГ) и 32 пациента без сердечно-сосудистых заболеваний. Выполнена оценка показателей углеводного обмена, мышечной массы и силы, уровня предшественника мозгового натрийуретического пептида, эхокардиографического исследования, теста шестиминутной ходьбы. Установлено, что у больных АГ с низким содержанием мышечной ткани и силы мышц достоверно повышены показатели инсулинорезистентности, более выражены признаки дисфункции миокарда ЛЖ и ФК ХСН. Одной из вероятных причин указанных патологических состояний служат нарушения энергетического гомеостаза, обусловленные ухудшением поступления глюкозы в мышечные клетки сердца и скелетной мускулатуры.

Topics: Aged; Carbohydrate Metabolism; Echocardiography; Energy Metabolism; Female; Heart Failure; Humans; Hypertension; Insulin Resistance; Male; Muscle Strength; Muscle, Skeletal; Natriuretic Peptide, Brain; Sarcopenia; Statistics as Topic; Walk Test

Arterial hypertension is a main determinant of arterial remodelling and atherosclerosis. Coronary artery calcium score and carotid intima-media thickness are recognized indices of vascular remodelling. Established biohumoral markers for the diagnosis of atherosclerosis are still lacking in asymptomatic subjects with hypertension.. We aimed to test the association of plasma N-terminal pro B-type natriuretic peptide concentrations with either coronary artery calcium score or carotid intima-media thickness in asymptomatic hypertensive subjects.. We conducted a case-control study on 436 hypertensi.ve and 436 age/sex-matched normotensive subjects from the population of the Montignoso HEart and Lung Project, a community-based study of asymptomatic general population ≥45 years. Subjects underwent N-terminal pro B-type natriuretic peptide measurement, echocardiography and evaluation of coronary artery calcium score and carotid intima-media thickness.. Hypertensive subjects had higher median coronary artery calcium score (60 (interquartile range, 30-112) vs. 15 (interquartile range 3-70) Agatson units, p = 0.007), carotid intima-media thickness (8.6 (interquartile range 7.5-9.1) vs. 7.9 (7.1-8.4) µm, p < 0.001) and indexed left ventricular mass (101 (interquartile range 82-126) vs. 87 (63-91) mg/m2, p = 0.03) than controls, with no differences in left ventricular ejection fraction, diameters, E/E', left atrial area. N-terminal pro B-type natriuretic peptide concentrations were higher in hypertensive subjects with either coronary artery calcium score (p = 0.008) or carotid intima-media thickness >75th (p < 0.006) percentile and highest in combined coronary artery calcium score/carotid intima-media thickness >75th percentile (p = 0.021). In multivariable analysis, N-terminal pro B-type natriuretic peptide independently predicted either coronary artery calcium score or carotid intima-media thickness >75th percentile, but only in hypertensive subjects (odds ratio = 1.87, 95% confidence interval 1.30-2.74, p = 0.001 and odds ratio = 1.99, 95% confidence interval 1.43-2.76, p = 0.001).. In asymptomatic subjects with hypertension, N-terminal pro B-type natriuretic peptide is a marker of hypertension-mediated preclinical vascular disease.

Topics: Asymptomatic Diseases; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Case-Control Studies; Coronary Angiography; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography, Doppler; Vascular Calcification; Vascular Remodeling

Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing.. In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography.. LV mass index significantly correlated with IAD (r = 0.203, P < 0.05), but not with AHI. Multivariate linear regression analyses showed that IAD, brain natriuretic peptide (BNP), and age are independent variables affecting the LV mass index (β = 0.262, 0.237, and 0.173, respectively, P < 0.05). IAD was the one and only determinant among the indices of sleep-disordered breathing.. Nocturnal intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea.

Topics: Adult; Age Factors; Cross-Sectional Studies; Echocardiography; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypoxia; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Sleep Apnea, Obstructive

There is increasing evidence that left atrial dysfunction or cardiopathy is associated with ischemic stroke risk independently of atrial fibrillation. We aimed to determine the prevalence of atrial cardiopathy biomarkers in patients with cryptogenic stroke.. We included consecutive patients with ischemic stroke enrolled in the New York Columbia Collaborative Specialized Program of Translational Research in Acute Stroke registry between December 1, 2008, and April 30, 2012. Medical records were reviewed and patients with a diagnosis of cryptogenic stroke were identified. Atrial cardiopathy was defined as at least one of the following: serum N-terminal probrain natriuretic peptide (NT-proBNP) level greater than 250 pg/mL, P-wave terminal force velocity in lead V1 (PTFV1) on electrocardiogram (ECG) greater than 5000 µV⋅ms, or severe left atrial enlargement (LAE) on echocardiogram. We compared clinical, echocardiographic, and radiological characteristics between patients with and without atrial cardiopathy.. Among 40 patients with cryptogenic stroke, 63% had at least one of the biomarkers of atrial cardiopathy; 49% had elevated NT-proBNP levels, 20% had evidence of increased PTFV1 on ECG, and 5% had severe LAE. Patients with atrial cardiopathy were more likely to be older (76 versus 62 years, P = .012); have hypertension (96% versus 33%, P < .001), hyperlipidemia (60% versus 27%, P = .05), or coronary heart disease (28% versus 0%, P = .033); and less likely to have a patent foramen ovale (4% versus 40%, P = .007).. There is a high prevalence of biomarkers indicative of atrial cardiopathy in patients with cryptogenic stroke. Clinical trials are needed to determine whether these patients may benefit from anticoagulation to prevent stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Function, Left; Biomarkers; Brain Ischemia; Cardiomegaly; Comorbidity; Coronary Disease; Cross-Sectional Studies; Electrocardiography; Female; Foramen Ovale, Patent; Heart Diseases; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prevalence; Prospective Studies; Registries; Smoking; Ultrasonography; Young Adult

The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care.. NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 ± 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 ± 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction.. Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014).. NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

Topics: Age Factors; Aged; Asymptomatic Diseases; Biomarkers; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Primary Health Care; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Time Factors

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.. Among 8,402 participants without prevalent CVD at visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).. Over a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57-2.46]) and NTproBNP >125 pg/mL (1.61 [1.29-1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07-0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95-1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59-2.50] and 2.80 [2.34-3.35], respectively).. Abnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.

Topics: Atherosclerosis; Biomarkers; Diabetes Complications; Diabetes Mellitus; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Factors; Troponin T

Data about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited.. The records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use.. Eight hundred fifty eight patients [10.6%, 95% CI (10 to 11.3%)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0% vs. 0.9%, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6% vs. 3.2%, p = 0.001) and in-hospital mortality (30.8% vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates.. Inotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study.

Topics: Acute Disease; Administration, Intravenous; Aged; Cardiotonic Agents; Comorbidity; Creatine Kinase, MB Form; Disease Progression; Dyslipidemias; Female; Heart Arrest; Heart Failure; Hospital Mortality; Hospitalization; Humans; Hyperglycemia; Hypertension; Intra-Aortic Balloon Pumping; Intubation, Intratracheal; Length of Stay; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Percutaneous Coronary Intervention; Population Growth; Qatar; Registries; Renal Insufficiency, Chronic; Respiration, Artificial; Retrospective Studies; Tachycardia, Ventricular

Phase contrast (PC) cine-magnetic resonance imaging (MRI) of the coronary sinus allows for noninvasive evaluation of coronary flow reserve (CFR), which is an index of left ventricular microvascular function. The objective of this study was to investigate coronary flow reserve in patients with heart failure with preserved ejection fraction (HFpEF).. We studied 25 patients with HFpEF (mean and SD of age: 73±7 years), 13 with hypertensive left ventricular hypertrophy (LVH) (67±10 years), and 18 controls (65±15 years). Breath-hold PC cine-MRI images of the coronary sinus were obtained to assess blood flow at rest and during ATP infusion. CFR was calculated as coronary sinus blood flow during ATP infusion divided by coronary sinus blood flow at rest. Impairment of CFR was defined as CFR <2.5 according to a previous study. The majority (76%) of HFpEF patients had decreased CFR. CFR was significantly decreased in HFpEF patients in comparison to hypertensive LVH patients and control subjects (CFR: 2.21±0.55 in HFpEF vs 3.05±0.74 in hypertensive LVH, 3.83±0.73 in controls; P<0.001 by 1-way ANOVA). According to multivariable linear regression analysis, CFR independently and significantly correlated with serum brain natriuretic peptide level (β=-68.0; 95% CI, -116.2 to -19.7; P=0.007).. CFR was significantly lower in patients with HFpEF than in hypertensive LVH patients and controls. These results indicated that impairment of CFR might be a pathophysiological factor for HFpEF and might be related to HFpEF disease severity.

Topics: Adenosine Triphosphate; Aged; Aged, 80 and over; Biomarkers; Blood Flow Velocity; Breath Holding; Case-Control Studies; Chi-Square Distribution; Coronary Sinus; Female; Fractional Flow Reserve, Myocardial; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Magnetic Resonance Imaging, Cine; Male; Multivariate Analysis; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Regional Blood Flow; Severity of Illness Index; Stroke Volume; Vasodilator Agents; Ventricular Function, Left

It is important to determine the usage of anticoagulants by defining the actual risk of cardioembolic stroke in patients with old myocardial infarction. In the present study, we aimed to more precisely evaluate the risks of each segment associated with cardioembolic stroke using a 16-segment model. The usage of the plasma brain natriuretic peptide (BNP) associated with cardioembolic stroke was also evaluated in comparison with a left ventricle ejection fraction less than 40%.. There were a total of 190 ischemic stroke patients who had premorbid myocardial infarction. The study included a total of 143 ischemic stroke patients with old myocardial infarction who were available for evaluation and excluded patients with atrial fibrillation or acute myocardial infarction. Their left ventricle wall motion abnormality and the level of plasma BNP at their admission were analyzed.. Hypertension and a plasma BNP level of 206.9 pg/mL or higher, determined from the receiver operating characteristic curve, were independently associated with cardioembolic stroke (χ(2) = 35.6, R(2) = .30, P < .001). Adjusting for these factors, statistically independent high risk was observed at the basal-inferior, basal-inferolateral, mid-anterior, mid-anteroseptal, apical-anterior, and apical-septal left ventricles.. High plasma BNP levels and left ventricular wall motion abnormalities in the segments perfused with left anterior descending coronary artery or right coronary artery show a high risk for cardioembolic stroke in patients with old myocardial infarction. Considering these factors, it could be possible to more precisely define the risk of cardioembolic stroke and to perform appropriate antithrombotic treatments in old myocardial infarction patients.

Topics: Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Biomechanical Phenomena; Chi-Square Distribution; Cross-Sectional Studies; Decision Support Techniques; Echocardiography; Female; Humans; Hypertension; Intracranial Embolism; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; ROC Curve; Stroke; Stroke Volume; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left

Women with chronic kidney disease (CKD) and chronic hypertension (CHT) frequently develop superimposed pre-eclampsia, but distinction from pre-existing disease is challenging. Plasma placental growth factor (PlGF), B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and serum relaxin concentrations were quantified in a longitudinal prospective cohort of 121 women with CKD: 44 with chronic hypertension, and 79 healthy controls. Biomarker concentrations were compared with 32 women with pre-eclampsia without pre-existing disease. Test performance was evaluated for diagnosis of superimposed pre-eclampsia requiring delivery within 14 days of sampling. PlGF was evaluated as a promising marker in a validation cohort of women with suspected pre-eclampsia (29 with CKD; 94 with chronic hypertension; 29 with superimposed pre-eclampsia requiring delivery within 14 days) and compared with women without pre-existing disease (290 with no pre-eclampsia and 176 with pre-eclampsia requiring delivery within 14 days). From 20 and up to 42 weeks of gestation, lower maternal PlGF concentrations had high diagnostic accuracy for superimposed pre-eclampsia requiring delivery within 14 days (receiver operator characteristic 0.85) and confirmed in the validation cohort. The other plasma and serum biomarkers were not discriminatory. Thus, plasma PlGF concentrations could potentially help guide clinical decision making regarding admission and delivery for superimposed pre-eclampsia.

Topics: Acute Kidney Injury; Adult; Biomarkers; Case-Control Studies; Female; Gestational Age; Humans; Hypertension; Lipocalin-2; Longitudinal Studies; Natriuretic Peptide, Brain; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Relaxin; Renal Insufficiency, Chronic

Expression of miR-154 is upregulated in the diseased heart and was previously shown to be upregulated in the lungs of patients with pulmonary fibrosis. However, the role of miR-154 in a model of sustained pressure overload-induced cardiac hypertrophy and fibrosis had not been assessed. To examine the role of miR-154 in the diseased heart, adult male mice were subjected to transverse aortic constriction for four weeks, and echocardiography was performed to confirm left ventricular hypertrophy and cardiac dysfunction. Mice were then subcutaneously administered a locked nucleic acid antimiR-154 or control over three consecutive days (25 mg/kg/day) and cardiac function was assessed 8 weeks later. Here, we demonstrate that therapeutic inhibition of miR-154 in mice with pathological hypertrophy was able to protect against cardiac dysfunction and attenuate adverse cardiac remodelling. The improved cardiac phenotype was associated with attenuation of heart and cardiomyocyte size, less cardiac fibrosis, lower expression of atrial and B-type natriuretic peptide genes, attenuation of profibrotic markers, and increased expression of p15 (a miR-154 target and cell cycle inhibitor). In summary, this study suggests that miR-154 may represent a novel target for the treatment of cardiac pathologies associated with cardiac fibrosis, hypertrophy and dysfunction.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Cyclin-Dependent Kinase Inhibitor p15; Disease Models, Animal; Echocardiography; Hypertension; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Natriuretic Peptide, Brain; Oligonucleotides; Pulmonary Fibrosis; Ventricular Remodeling

Frailty, a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability, is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between frailty and hypertensive end-organ damage is not fully established.. We performed a cross-sectional study to investigate the association between frailty and end-organ damage in 1125 apparently healthy middle-aged to elderly subjects. We performed a simple frailty (SF) score that was easily obtainable in the office, in combination with low hand grip power and short one-leg standing (OLS) time. The association between SF score and hypertensive end-organ damage and other frailty-related parameters was evaluated. Odds ratio of SF score 1 to score 0 for the presence of hypertension was 1.9 [1.4-2.5, p<.0001] and that of SF score 2 was 3.3 [2.1-5.3, p<.0001]. SF score was also significantly associated with brachial-ankle pulse wave velocity (baPWV) and central pulse pressure (PP2). SF score was significantly associated with higher frailty index calculated from 21 parameters, lower cognitive test score, % vital capacity, skeletal muscle mass, and thigh muscle cross-sectional area. SF score was positively associated with stage of brain white matter hyperintenisty, plasma levels of B-type natriuretic peptide, and urinary protein excretion, even after correction for confounding parameters including baPWV and PP2.. These findings indicate that frailty is significantly associated with end-organ damage in elderly subjects. SF score may be a useful clinical tool to identify frail subjects and advanced end-organ damage in elderly subjects.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Cross-Sectional Studies; Female; Frail Elderly; Geriatric Assessment; Hand Strength; Humans; Hypertension; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Odds Ratio; Sarcopenia; White Matter

Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb-/-) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb-/- females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb-/- female. This study highlights BNP's vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis.

Topics: Animals; Blood Pressure; Female; Humans; Hypertension; Male; Mesenteric Arteries; Natriuretic Peptide, Brain; Polyarteritis Nodosa; Rats, Inbred Dahl; Sex Factors; Time Factors; Vascular Remodeling; Vasculitis

Compared with heart failure (HF) with reduced ejection fraction (HF-REF), the diagnosis of HF with preserved EF (HF-PEF) is more challenging. The aim of the study was to assess the prevalence of HF-PEF among patients hospitalized for HF, to evaluate the pertinence of HF-PEF diagnosis and to compare HF-PEF and HF-REF patients with respect to outcomes. The analysis included 661 Polish patients hospitalized for HF, selected from the European Society of Cardiology (ESC)-HF Long-Term Registry. Patients with an EF of ≥50% were included in the HF-PEF group and patients with an EF of <50% - in the HF-REF group. The primary end point was all-cause death at 1 year. The secondary end point was a composite of all-cause death and rehospitalization for HF at 1 year. HF-PEF was present in 187 patients (28%). Of those 187 patients, mitral inflow pattern was echocardiographically assessed in 116 patients (62%) and classified as restrictive/pseudonormal in 37 patients (20%). Compared with HF-REF subjects, patients with HF-PEF were older, more often female, and had a higher prevalence of hypertension, atrial fibrillation and sleep apnea. Despite lower B-type natriuretic peptide concentrations and lower prevalence of moderate-to-severe mitral regurgitation in patients with HF-PEF, congestive symptoms at admission were as severe as in patients with HF-REF. There were no significant differences in in-hospital mortality between the HF groups. One-year mortality was high in both groups (17% in HF-PEF vs 21% in HF-REF, p = 0.22). There was a trend toward a lower frequency of the secondary end point in the HF-PEF group (32% vs 40%, p = 0.07). In conclusion, in clinical practice, even easily obtainable echocardiographic indexes of diastolic dysfunction are relatively rarely acquired. One-year survival rate of patients with HF-PEF is not significantly better than that of patients with HF-REF.

Topics: Age Distribution; Aged; Aged, 80 and over; Atrial Fibrillation; Case-Control Studies; Comorbidity; Disease Progression; Echocardiography; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Poland; Prevalence; Prognosis; Registries; Severity of Illness Index; Sex Distribution; Sleep Apnea Syndromes; Stroke Volume

The purpose of this study was to describe the prevalence and prognosis of HF stages in the community; to evaluate if preclinical HF stages are characterized by elevation of pro-inflammatory (C-reactive protein), neurohormonal activation (B-type natriuretic peptide, renin and aldosterone), and cardiac stress biomarkers (high-sensitivity troponin I, ST-2, and growth differentiation factor-15).. The American Heart Association/American College of Cardiology heart failure (HF) classification has 3 stages. Knowledge regarding the community burden of HF stages is limited, and data on the biomarker profile associated with HF stages are scarce, although higher concentrations of certain biomarkers are associated with preclinical HF.. We evaluated 6,770 participants (mean age 51 years; 54% women) from the Framingham Study, defining 4 stages: 1) healthy: no risk factors; 2) stage A: presence of HF risk factors (hypertension, diabetes, obesity, coronary artery disease), no cardiac structural/functional abnormality; 3) stage B: presence of prior myocardial infarction, valvular disease, left ventricular (LV) systolic dysfunction, LV hypertrophy, regional wall motion abnormality, or LV enlargement; 4) stage C/D: prevalent HF.. The prevalence of HF stages A and B were 36.5% and 24.2%, respectively, rising with age (odds ratio: 1.70 [95% confidence interval: 1.64 to 1.77] per decade increment). In age- and sex-adjusted models, we observed a gradient of increasing biomarker levels across HF stages (p < 0.05; n = 3,416). Adjusting for age and sex, mortality rose across HF stages (232 deaths, mean follow-up 7 years), with 2- and 8-fold mortality risks for stages B and C/D, respectively, compared with healthy.. Approximately 60% of our sample has preclinical HF, and those in stage B had higher concentrations of HF biomarkers and experienced a substantial mortality risk.

Topics: Adult; Aged; Aldosterone; C-Reactive Protein; Coronary Artery Disease; Diabetes Mellitus; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Odds Ratio; Prevalence; Prognosis; Renin; Risk Factors; Severity of Illness Index; Troponin I; United States; Ventricular Dysfunction, Left

This multicenter study investigated the effect of renal denervation therapy (RDN) on the heart failure related biomarkers NT-proBNP, ST-2, galectin-3 and hs-TnI.. We included 157 patients with resistant hypertension undergoing RDN. Blood sampling was performed before and 6 months after RDN.. Six months after RDN systolic blood pressure (BP) was reduced by 24 mmHg. Biomarker concentrations were not changed after RDN, except a small increase of hs-TnI by 0.3 pg/ml. In individuals with high baseline BP, we observed a BP reduction of 45 mmHg and a decrease of hs-TnI concentrations by 1.2 pg/ml.. In this multicenter analysis RDN did significantly reduce systolic BP. However, NT-proBNP, ST-2, galectin-3 and hs-TnI did not correspond to BP reduction 6 months after RDN.

Topics: Aged; Biomarkers; Blood Pressure; Echocardiography; Female; Galectin 3; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Interleukin-1 Receptor-Like 1 Protein; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Troponin I

Black populations exhibit lower concentrations of the cardioprotective peptide, insulin-like growth factor-1 (IGF-1), and are more prone to develop hypertensive heart disease than whites. We therefore determined whether lower IGF-1 in black individuals relates to a marker of cardiac overload and systolic dysfunction, namely N-terminal prohormone B-type natriuretic peptide (NT-proBNP).. We included 160 black and 195 white nondiabetic South African men and women (aged 44·4 ± 9·81 years) and measured ambulatory blood pressure, NT-proBNP, IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3).. Although the black group presented elevated ambulatory blood pressure accompanied by lower IGF-1 compared to the white group (all P < 0·001), we found similar NT-proBNP concentrations (P = 0·72). Furthermore, in blacks we found a link between NT-proBNP and systolic blood pressure (SBP) (R(2) = 0·37; β = 0·28; P < 0·001), but not with IGF-1. In the white group, NT-proBNP was inversely associated with IGF-1 (R(2) = 0·39; β = -0·22; P < 0·001) after adjusting for covariates and potential confounders. As IGF-1 is attenuated in diabetes, we added the initially excluded patients with diabetes (n = 38), and the aforementioned associations remained robust.. Contrary to the white group, we found no association between NT-proBNP and IGF-1 in black adults. Our findings suggest that SBP and other factors may play a greater contributory role in cardiac pathology in blacks.

Topics: Adult; Black People; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; South Africa; White People

Cardiac allograft vasculopathy (CAV) still remains to be one of the most important limiting factors for heart transplant recipients' long-term survival. The aim of our study was to identify the perioperative risk factors impacting the occurrence of CAV during the long-term follow-up.. We retrospectively analysed the data from 198 consecutive adult patients, who underwent heart transplantation between 2007 and 2012, in whom at least one routine coronarography (CAG) was performed. CAV onset was defined as any lesion seen at least at one routine CAG.. The average follow-up was 63.6 ± 14.7 months. The frequency of CAV in the analysed population was 36 (18.1%). Multivariate stepwise logistic regression analysis confirmed that NT-proBNP plasma concentration directly before heart transplant [logNT-proBNP OR = 16.455 (4.587-31.036), P < .0001], fibrinogen plasma concentration a month after heart transplant [OR = 1.022 (1.009-1.035), P < .001] and occurrence of diabetes [OR = 12.355 (1.417-35.750), P < .001], were independent predictors of CAV. Area under the ROC curves (AUC) indicated a well discriminatory power of plasma fibrinogen [AUC 0.9278, P < .001] and plasma NTproBNP concentration [AUC 0.9514, P < .001] in CAV prediction. The optimal cut-off value of fibrinogen was 509 mg/dL, and of NT-proBNP was 10080 pg/mL.. Our data show that NT-proBNP and fibrinogen plasma concentrations as well as occurence of diabetes, both preexisting and new onset after heart transplant can be used to identify patients at risk of developing CAV.

Topics: Allografts; Diabetic Angiopathies; Female; Follow-Up Studies; Graft Rejection; Heart Diseases; Heart Transplantation; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Risk Factors; Time Factors; Transplantation, Homologous; Treatment Outcome

Natriuretic peptide (NP) levels are routinely employed as useful diagnostic and prognostic tools in the evaluation of patients with heart failure (HF). As hospitalization is the major consumer of healthcare resources, the prognostic power of admission NPs with regard to the duration of hospitalization deserves further investigation.. We assessed retrospectively the association between NP values sampled shortly following unplanned admission and the duration of hospitalization in 2978 patients admitted to a cardiology department. Duration of hospitalization (hours) and survival were determined by interrogation of the electronic medical records system. Associations with peptide levels were estimated using regression models and receiver operating characteristic (ROC) analysis. The results demonstrate a significant positive relationship between NP levels and the duration of hospitalization, after adjusting for age (P < 0.001). The median duration of hospitalization for the lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and 236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and 390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78% and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive of all-cause mortality.. The results quantify the strong relationship between NP levels taken following an unplanned admission to a cardiology department and the duration of hospitalization. This information permits improved identification of a patient population likely to require a prolonged hospital stay and consume more healthcare resources. Such patients may require a more aggressive diagnostic, treatment, and management strategy.

Topics: Aged; Arrhythmias, Cardiac; Cardiology Service, Hospital; Cardiomyopathies; Female; Heart Failure; Hospitalization; Hospitals, University; Humans; Hypertension; Length of Stay; Linear Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Proportional Hazards Models; Respiratory Tract Infections; Retrospective Studies; ROC Curve

Topics: Biomarkers; Cardiovascular Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

There are few data comparing the patient characteristics and outcomes of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) in Asian cohorts. We aimed to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian HFpEF cohort in comparison to an HFrEF cohort. We conducted a retrospective observational study of 1,978 patients discharged from Changi General Hospital, Singapore with a primary diagnosis of HF from 2009 to 2013. About 29% of discharges had HFpEF. Patients with HFpEF were more likely to be women, older age, and have a higher prevalence of hypertension. There were no significant differences in the absolute rates of 30-day outcomes between the 2 groups. The absolute rate of death at 1 year was similar in HFrEF and HFpEF at 17% and 15%, respectively (p = 0.3). After multivariate adjustment, there was no difference in the outcomes of the 2 groups. Atrial fibrillation at baseline was a predictor of death or HF hospitalization in HFpEF but not HFrEF (interaction p = 0.003). In conclusion, in this study of a Southeast Asian population with well-defined HF, we found that the clinical profile of patients with HF was similar to that in the West and 30-day and 1-year mortality and morbidity were not significantly different between cohorts.

Topics: Aged; Aged, 80 and over; Asia, Southeastern; Asian People; Atrial Fibrillation; Cause of Death; Cohort Studies; Comorbidity; Echocardiography; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Sex Factors; Singapore; Stroke Volume

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with cardiovascular morbidity and mortality, which can be improved by using continuous positive airway pressure (CPAP) therapy. However, the pathophysiological links between the two kinds of disease and the mechanism of the CPAP effect remain incompletely understood. We aimed to inquire into the myocardial involvement in this relationship. We suggested that serum brain natriuretic peptide (BNP) is sensitive enough to detect myocardial stress caused by OSAHS.. Sixty-four subjects without cardiovascular disease (21 controls, 24 normotensive OSAHS patients, and 19 hypertensive OSAHS patients) were analyzed for serum BNP at baseline and serially over 6 months. CPAP was applied to 23 patients with severe OSAHS.. At baseline, the serum BNP levels were significantly higher (p=0.0001) in the OSAHS group (22.3±14.79 pg/ml) than in the control group (9.2±6.75 pg/ml). Increased serum BNP levels were significantly associated with mean transcutaneous oxygen saturation (SpO2) (p<0.0001), minimal SpO2 (p=0.002), oxygen desaturation index (p=0.001), and total sleep time spent with SpO2 lower than 90% (p=0.002). All patients with elevated BNP levels (≥37 pg/ml) had moderate or severe OSAHS (11/43 OSAHS patients). The more severe the OSAHS, the higher the BNP levels were. However, only the difference between severe and mild OSAHS was statistically significant (p=0.029). Hypertensive OSAHS patients had the highest baseline BNP levels (27.7±16.74 pg/ml). They were significantly higher (p=0.001) than in normotensive OSAHS patients (18±11.72 pg/ml) (p=0.039) and the controls (9.2±6.75 pg/ml). As compared with baseline, treatment with CPAP significantly decreased BNP levels in both hypertensive and normotensive OSAHS patients (respectively, from 36±16.10 to 29.7±14.29 pg/ml, p<0.001, and from 20±10.09 to 16±8.98 pg/ml, p<0.001). In contrast, the BNP levels slightly increased in the controls (from 9.2±6.75 to 9.5±7.02 pg/ml, p=0.029), but there was no statistically significant difference in comparison with the baseline value. The effect of CPAP on BNP levels was more marked in patients with higher baseline BNP levels and those with the most prolonged nocturnal desaturation (p=0.001, r=0.65). It was also more marked in hypertensive OSHAS patients (p=0.015, r=0.72) in comparison with normotensive OSAHS patients (p=0.03, r=0.62).. BNP seems to be sensitive enough to detect myocardial stress caused by OSAHS. As such, it is a potential marker for screening of preclinical cardiovascular damage in patients with untreated OSAHS. Application of CPAP decreases levels significantly in normotensive and particularly in hypertensive OSAHS. These findings are consistent with previous results suggesting the potential benefits of CPAP on cardiovascular outcome in OSAHS patients.

Topics: Adult; Cardiovascular Diseases; Continuous Positive Airway Pressure; Cross-Sectional Studies; Early Diagnosis; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive

The circulating concentration of cardiac troponin I (cTnI) is an index of subclinical myocardial injury in several patient populations and in the general population. Erectile dysfunction is associated with greater risk for cardiovascular events, but the association with subclinical myocardial injury is not known. We aimed to test the hypothesis that the presence and severity of erectile dysfunction is associated with greater concentrations of cTnI in the general population. The presence and severity of erectile dysfunction was assessed by administering the International Index of Erectile Function 5 (IIEF-5) questionnaire to 260 men aged 30 to 65 years recruited from a population-based study. Concentrations of cTnI were determined by a high-sensitivity (hs) assay. Hs-cTnI levels were significantly higher in subjects with than in those without erectile dysfunction (median 2.9 vs 1.6 ng/l; p <0.001). Men with erectile dysfunction (i.e., IIEF-5 sum score <22) were also significantly older; had a higher systolic blood pressure, lower estimated glomerular filtration rate, higher augmentation index and N-terminal pro-B-type natriuretic peptide; and had a higher prevalence of hypertension, diabetes mellitus, and previous coronary artery disease than subjects without erectile dysfunction. These covariates were adjusted for in a multivariate linear regression model, yet the IIEF-5 sum score remained significantly negatively associated with the hs-cTnI concentration (standardized β -0.206; p <0.001). In conclusion, the presence and severity of erectile dysfunction is associated with circulating concentrations of hs-cTnI, indicating subclinical myocardial injury independently of cardiovascular risk factors, endothelial dysfunction and heart failure biomarkers.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Diabetes Mellitus; Erectile Dysfunction; Glomerular Filtration Rate; Heart Diseases; Humans; Hypertension; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Severity of Illness Index; Surveys and Questionnaires; Troponin I

To study the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with several brain MRI markers of brain vascular disease in a sample of participants free of stroke and dementia.. NT-proBNP plasma level was determined by means of a sandwich immunoassay method in a cohort study comprising 278 hypertensive patients. The presence of silent brain infarcts, brain microbleeds, enlarged perivascular spaces, and white matter hyperintensity volumes was assessed by brain MRI. We performed univariate and multivariate analyses to determine whether NT-proBNP was independently associated with these imaging markers, individually or combined.. Median age was 63 years, and 41.4% were women. NT-proBNP remained independently associated with silent brain infarcts (odds ratio [OR] per 1-SD increase in NT-proBNP 2.11, 95% confidence interval [CI] 1.44-3.10), brain microbleeds (OR 1.79, 95% CI 1.15-2.78), basal ganglia enlarged perivascular spaces (OR 1.55, 95% CI 1.12-2.15), and white matter hyperintensity volumes (β 1.60, 95% CI 0.47-2.74), even after controlling for vascular risk factors, cardiovascular risk, atrial fibrillation, previous heart disease, duration of hypertension, and preventive treatments. A score combining several imaging markers was also related to NT-proBNP levels (common OR per 1-SD increase 1.74, 95% CI 1.21-2.50).. NT-proBNP is independently associated with silent cerebrovascular lesions and could be a surrogate marker of vascular brain damage in hypertension.

Topics: Aged; Biomarkers; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors

The aim of this study was to evaluate the association of NT-proBNP with clinical and hemodynamic assessment in 156 patients with arterial hypertension. NT-proBNP correlated positively with, i.e. age (r=0.310, p=0.00008), mean blood pressure (MBP; r=0.199, p=0.0136), Heather index (HI; r=0.375, p<0.00001) and negatively with thoracic fluid content (TFC; r=-0.300, p=0.0002). The patients with higher NT-proBNP were older (46.1 versus 40.6 years, p=0.001), with higher MBP (102.6 versus 98.5 mm Hg, p=0.0043), HI (14.54 versus 11.93 Ohm s2, p=0.009) and lower TFC (27.5 versus 29.4 1/kOhm, p=0.0032). The independent predictors of higher NT-proBNP were: age, MBP and HI.

Topics: Adult; Biomarkers; Cardiography, Impedance; Disease Progression; Echocardiography; Essential Hypertension; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Retrospective Studies; Severity of Illness Index

To measure the plasma concentrations of adrenomedullin (ADM),atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP), and investigate their pathophysiological functions in patients with primary aldosteronism (PA). Between June 2006 and December 2012, we recruited 25 patients with untreated PA, 30 patients with untreated low-renin essential hypertension (EH), and 35 healthy control subjects. The plasma concentrations of ADM, ANP, and BNP were measured in all the subjects. After 4 weeks of effective antihypertensive therapy with slow-release nifedipine, the three peptides were measured again in the PA and low-renin EH subjects. Unilateral laparoscopic adrenalectomy was performed in all the PA patients; 2 weeks after surgery, the three peptides were measured again. The PA patients had significantly higher plasma concentrations of ADM, ANP, and BNP than the low-renin EH and control subjects. The low-renin EH and control subjects significantly differed in the concentrations of the three peptides between low-renin EH and control subjects. ADM was the most important peptide associated with aldosterone or blood pressure in the PA patients. Plasma ADM concentration was not only correlated with plasma aldosterone concentrations, but also with systolic and diastolic blood pressures, and plasma ANP and BNP concentrations in the PA patients. By contrast, ADM concentration was not related to blood urea nitrogen levels, serum creatinine levels, and glomerular filtration rates. After antihypertensive treatment, the concentrations of the three peptides significantly decreased in the low-renin EH patients, but remained unchanged in the PA subjects. However, these concentrations significantly decreased 2 weeks after laparoscopic adrenalectomy in the PA subjects. ADM, ANP, and BNP possibly participate in the mechanisms counteracting further elevation of blood pressure or plasma volume expansion resulting from aldosterone hypersecretion in PA patients. An ADM/aldosterone local regulatory mechanism may be involved in regulating adrenal adenoma functions.

Topics: Adrenalectomy; Adrenomedullin; Adult; Atrial Natriuretic Factor; Essential Hypertension; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nifedipine; Vasodilator Agents

Both metabolic syndrome (MetS) and N-amino terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared with subjects who met none of the defining criteria of the MetS.. A case-cohort study from the non-diabetic population-based Casale Monferrato study was performed, after exclusion of all subjects with established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2)], and CRP values ≥3 mg/L. Cases (n = 161) with MetS were compared with all subjects within the cohort (n = 124) who were completely free of any component of the MetS. Serum NT-proBNP was centrally measured by immunoenzymatic assay.. NT-proBNP levels were significantly higher in cases than in control subjects [35.4 (15.5-98.2) vs 24.4 (11.7-49.6) pg/mL, p = 0.014]. In logistic regression analysis, compared with NT-proBNP values in the lower quartiles (≤49.64 pg/mL), higher values conferred odds ratio 4.17 (1.30-13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP, eGFR, and central obesity. This association was evident even after the exclusion of hypertensive subjects. Further adjustment for log-HOMA and diastolic blood pressure did not modify the strength of the association, while central obesity was a negative confounder.. Compared with people without any component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor diabetes, had increased NT-proBNP values, even if they were normotensive and although absolute values were still in the low range. The insulin resistance state did not mediate this association, while central obesity was a negative confounder.

Topics: Aged; Body Mass Index; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Hypertension; Insulin Resistance; Italy; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity, Abdominal; Overweight; Peptide Fragments; Prediabetic State; Prevalence; Severity of Illness Index; Up-Regulation; Waist Circumference

Recent reports have characterized virological and clinical features of the novel reassortant avian-origin influenza A (H7N9) virus. However, cardiovascular involvement during H7N9 infection is still unclear. In this study, we evaluate cardiac injury among H7N9-infected patients.. A total of 40 patients who were laboratory-confirmed with H7N9 infection were retrospectively included and grouped by Acute Physiology and Chronic Health Evaluation II (APACHE II) score into four subgroups I(0-10), II(11-20), III(21-30) and IV(31-71). Cardiovascular complications and markers of cardiac injury including creatinine kinase (CK), CK iso-enzyme (CK-MB), cardiac troponin I (cTNI) and brain natriuretic peptide (BNP) were assessed. Electrocardiogram (ECG) and echocardiography (ECHO) were also performed.. Half of patients manifested with cardiovascular complications, with hypotension (47.5%) and heart failure (40.0%) the most prevalent. CK, CK-MB and cTNI showed marked increase with H7N9 virus infection but significantly decreased after H7N9 viral tests turned negative. More than half of patients presented with an abnormal ECG, but most of them are benign changes. ECHO examination showed different degree of impairment of cardiac function. Pulmonary artery systolic pressure was increased in all groups. Cardiac damage was more evident in patients with higher APACHE II score.. H7N9 virus exerts a transient impairment on the cardiovascular system. Patients with a higher APACHE II score are more susceptible to cardiac damage.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Creatine Kinase; Echocardiography; Electrocardiography; Female; Heart Diseases; Humans; Hypertension; Influenza A Virus, H7N9 Subtype; Influenza, Human; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Partial Pressure; Retrospective Studies; Troponin I; Young Adult

In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading.. We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m(2)) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large-volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre-operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6-month visit, N-terminal pro-atrial NP (Nt-proANP) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre-operative visit (P<0.001). The rise in Nt-pro-ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for BNP and Nt-proBNP; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure (P=0.004) and heart rate (P<0.001), and an increase in mitral annular diastolic velocity (P=0.02).. In obese individuals, weight loss is associated with a substantial increase in the "setpoint" of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Echocardiography, Doppler; Enzyme-Linked Immunosorbent Assay; Female; Gastric Bypass; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Obesity, Morbid; Peptide Fragments; Postoperative Care; Preoperative Care; Prognosis; Sodium Chloride; Weight Loss

Although obtaining multiple home blood pressure (HBP) measurements on a single occasion was recommended in European and Japanese hypertension guidelines, the clinical implications of the differences in BP measurements on a single occasion have been uncertain.. Here, 4,149 patients with cardiovascular risk factors were enrolled. We asked the patients to measure their HBP 3 times on a single occasion each day over a 2-week period. We evaluated the target organ damage (TOD) indicators left ventricular mass index (LVMI), urinary albumin creatinine ratio, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro BNP), high-sensitive cardiac troponin, brachial-ankle pulse wave velocity (ba PWV), intima-media thickness, and estimated glomerular filtration rate (eGFR). The associations between TOD and the difference between the first home systolic BP (SBP) value and the average of the second and third home SBP values were assessed by multiple regression analyses with adjustment for covariates.. Compared to the quintile median, the TOD of the first-quintile patients (i.e., those with elevated the second and third home SBP values compared to the first value) were significantly higher BNP, higher NT-pro BNP, higher ba PWV, and lower eGFR. In a univariate analysis of variance, compared to the median quintile, the first-quintile patients had independently and significantly higher BNP, higher NT-pro BNP, and lower eGFR.. The patients with elevated the second and third home SBP values compared to the first value taken on a single occasion were likely to have deteriorated BNP, NT-pro BNP, and eGFR.

Topics: Aged; Biomarkers; Blood Pressure; Blood Pressure Determination; Disease Progression; Female; Glomerular Filtration Rate; Heart Diseases; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Risk Factors; Self Care

The role of the natriuretic peptides (NPs) in hypertension is complex. Thus, a higher blood NP concentration is a robust marker of pressure-induced cardiac damage in patients with hypertension, whereas genetically elevated NP concentrations are associated with a reduced risk of hypertension and overweight individuals presumably at high risk of hypertension have lower NP concentrations.. To investigate the associations between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), used as a surrogate marker for active BNP, and prevalent as well as 5-year incident hypertension in a Danish general population sample.. Cross-sectional and prospective population-based study.. At baseline, among 5,307 participants (51.3% women, mean age 46.0±7.9 years) with a complete set of data, we recorded 1,979 cases with prevalent hypertension (PHT). Among 2,389 normotensive participants at baseline with a complete set of data, we recorded 324 cases with incident hypertension (IHT) on follow-up 5 years later. In models adjusted for age, sex, lifestyle, social, dietary, anthropometric, pulmonic, lipid, metabolic and renal risk factors, as well as heart rate and baseline blood pressure (only incident model), one standard deviation increase in baseline log-transformed NT-proBNP concentrations was on one side associated with a 21% higher risk of PHT (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.13-1.30], P<0.001), and on the other side with a 14% lower risk of IHT (OR: 0.86 [95%CI:0.76-0.98], P = 0.020).. Higher serum concentrations of NT-proBNP associate with PHT whereas lower concentrations associate with IHT. This suggests that a lower amount of circulating BNP, resulting in diminished vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.

Topics: Adult; Blood Pressure; Cross-Sectional Studies; Denmark; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prospective Studies; Risk Factors

The study aimed to identify early echocardiographic and circulating biomarkers of heart failure (HF) in hypertensive patients with normal resting echocardiography. Echocardiography at rest and during exercise, and selected biomarkers were assessed in control group, dyspnea group, and HF group. On exercise dyspnea patients had lower early diastolic (E') and systolic (S') mitral annular velocity (12.8 ± 1.0 vs 14.9 ± 3.0 cm/sec and 9.3 ± 2.0 vs 10.9 ± 2.0 cm/sec, respectively), and higher E/E' ratio compared to control group (6.7 ± 1.0 vs 5.9 ± 1.0) (p < 0.05 for all comparisons). The level of N-terminal propeptide of procollagen type III (PIIINP) was significantly higher in dyspnea group than in controls (p = 0.01). Control and dyspnea patients had lower levels of cardiotrophin-1, cystatin C, syndecan-4, and N terminal-probrain natriuretic peptide than HF patients (all p ≤ 0.01). In multivariate analysis PIIINP (unadjusted odds ratio [OR] = 8.2, 95% confidence interval [Cl] 1.7-40.6; p = 0.001; adjusted OR = 8.7; 95%CI: 1.5-48.3; p = 0.001) and E/E' ratio on exercise (unadjusted OR = 1.8, 95%CI: 0.8-4.0; p = 0.033; adjusted OR = 2.0; 95%CI: 0.8-4.8; p = 0.012) were the only factors significantly associated with the presence of dyspnea. PIIINP is the first early biomarker for the HF development in patients with HA and normal resting echocardiography. Exertional echocardiography may indicate patients with incipient HF with preserved ejection fraction.

Topics: Aged; Biomarkers; Cytokines; Echocardiography; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is released by the heart in response to ventricular and auricular wall stress. Release of BNP is traditionally considered part of the body's protective mechanism against pressure overload by inducing vasodilatation and diuresis. More recent evidence demonstrates that BNP also promotes vessel wall stress and preliminary studies suggest that chronic increased levels may increase risk of hypertension. This study aimed to evaluate the prospective association of N-terminal BNP (NT-proBNP), a cleavage product of BNP, with risk of hypertension in the Atherosclerosis Risk in Communities cohort study.. We conducted a prospective analysis of 3,798 middle-aged participants in the ARIC study without hypertension at baseline (1996-1998). Using Cox proportional hazards models, we characterized the association between NT-proBNP at baseline and newly diagnosed hypertension for a maximum of 14 years of follow-up (median = 9 years).. We observed 2,113 new hypertension cases over the follow-up period. Higher baseline NT-proBNP was independently associated with an increased risk of hypertension. Adjusted hazard ratios for incident hypertension in the highest quartile compared to the lowest quartile of NT-proBNP at baseline was 1.24 (95% CI: 1.08-1.42). Each log-unit increase in NT-proBNP was associated with an 8% increased risk of hypertension (95% CI: 1.03-1.13).. Persons with elevated NT-proBNP, even with normal blood pressure at baseline, were at increased risk of developing hypertension. Our results suggest that elevated circulating BNP might contribute to the development of hypertension in previously normotensive individuals.

Topics: Cohort Studies; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; United States

Topics: Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments

Longitudinal associations between the aminoterminal pro-B-type natriuretic peptide (NT-proBNP) and incident hypertension are lacking.. We tested associations between baseline NT-proBNP (bNT-proBNP) and change in NT-proBNP (ΔNT-proBNP) (visit 3 NT-proBNP - bNT-proBNP, 3.2 years apart) with incident hypertension (SBP ≥ 140 and/or DBP ≥90 mmHg or taking antihypertensive medications). Incident hypertension was evaluated in 5596 individuals in the Multi-Ethnic Study of Atherosclerosis without hypertension at baseline (53% women, age range 45-84 years without overt cardiovascular disease) and follow-up for 9.5 years and in a subgroup (1550) who had bNT-proBNP less than 100 pg/ml and no hypertension at visit 3. Incident hypertension was regressed (proportional hazards) on quintiles of bNT-proBNP (range) (reference <19.2, 19.3-40.8, 40.9-70.9, 71-135.2, and >135.5) and also on ΔNT-proBNP categories (reference <-10, -10 to 10, >10 to 50, and >50 pg/ml). Hazard ratios were adjusted for age, race, sex, education, diabetes, obesity, left ventricle mass/height, SBP and DBP, interleukin-6, salt intake, estimated glomerular filtration rate, and exercise.. Compared with the reference category, hazard ratios (95% confidence interval) for incident hypertension compared with the first quintile of bNT-proBNP were 1.47 (1.13-1.93), 1.57 (1.18-2.09), 1.52 (1.12-2.06), and 2.36 (1.62-3.41). Hazard ratios for incident hypertension by categories of ΔNT-proBNP from 3.2 to 9.5 years follow-up were 0.98 (0.62-1.56), 1.13 (0.72-1.79), and 1.82 (1.07-3.12).. The development of hypertension tended to be preceded by elevated levels of bNT-proBNP or a substantial positive ΔNT-proBNP.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors

Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission.

Topics: Animals; Calcium Signaling; Cells, Cultured; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Cyclic Nucleotide Phosphodiesterases, Type 2; Heart Conduction System; Heart Rate; Hypertension; Isatin; Male; Natriuretic Peptide, Brain; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Recombinant Fusion Proteins; Second Messenger Systems; Stellate Ganglion; Sympathetic Nervous System; Synaptic Transmission

Topics: Animals; Cyclic Nucleotide Phosphodiesterases, Type 2; Heart Conduction System; Hypertension; Male; Natriuretic Peptide, Brain; Sympathetic Nervous System

To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA.. We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA.. A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055).. Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Topics: Aged; Angioplasty; Diabetes Mellitus; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Function Tests; Male; Natriuretic Peptide, Brain; Renal Artery; Renal Artery Obstruction; Renal Insufficiency; Risk Factors

Cardiovascular remodeling, as a hallmark of hypertension-induced pathophysiology, causes substantial cardiovascular morbidity and mortality. There is increasing evidence that has demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and cardiovascular diseases. In this study, 180- to 200-g SD rats treated with DOCA (120 mg/week sc with 1% NaCl and 0.2% KCl in drinking water) and GSP (150, 240, 384 mg/kg) or amlodipine (ALM) (5 mg/kg) for 4 weeks were recruited. The protective effects of GSP on blood pressure and cardiovascular remodeling in rats with DOCA-salt-induced hypertension were investigated. Our results indicated that DOCA-salt could induce hypertension, cardiovascular remodeling and dysfunction, oxidative stress and the release of endothelin-1 (ET-1) and could increase JNK1/2 and p38MAPK phosphorylation. GSP or ALM treatments significantly improved hypertension, cardiovascular remodeling and dysfunction and oxidative stress, restrained the release of ET-1 and down-regulated the JNK1/2 and p38MAPK phosphorylation. These findings demonstrate that GSP has protective effects against increase of blood pressure induced by DOCA-salt hypertension and cardiovascular remodeling by inhibiting the reactive oxygen species/mitogen-activated protein kinase pathway via restraining the release of ET-1.

Topics: Animals; Blood Pressure; Cardiovascular System; Desoxycorticosterone Acetate; Endothelin-1; Grape Seed Extract; Hydroxyproline; Hypertension; Male; Malondialdehyde; Natriuretic Peptide, Brain; Nitric Oxide; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac failure. Reduction of LVH has beneficial effects on the heart. LVH is associated with shift in energy substrate preference from fatty acid to glucose, mediated by down regulation of peroxisome proliferator-activated receptor-alpha (PPAR-α). As long-term dependence on glucose can promote adverse cardiac remodeling, it was hypothesized that, prevention of metabolic shift by averting down regulation of PPAR-α can reduce cardiac remodeling in spontaneously hypertensive rat (SHR). Cardiac response to stimulation of PPAR-α presumably depends on the type of ligand used. Therefore, the study was carried out in SHR, using two different PPAR-α ligands. SHR were treated with either fenofibrate (100 mg/kg/day) or medium-chain triglyceride (MCT) Tricaprylin (5% of diet) for 4 months. Expression of PPAR-α and medium-chain acylCoA dehydrogenase served as markers, for stimulation of PPAR-α. Both ligands stimulated PPAR-α. Decrease of blood pressure was observed only with fenofibrate. LVH was assessed from heart-weight/body weight ratio, histology and brain natriuretic peptide expression. As oxidative stress is linked with hypertrophy, serum and cardiac malondialdehyde and cardiac 3-nitrotyrosine levels were determined. Compared to untreated SHR, LVH and oxidative stress were lower on supplementation with MCT, but higher on treatment with fenofibrate. The observations indicate that reduction of blood pressure is not essentially accompanied by reduction of LVH, and that, progressive cardiac remodeling can be prevented with decrease in oxidative stress. Contrary to the notion that reactivation of PPAR-α is detrimental; the study substantiates that cardiac response to stimulation of PPAR-α is ligand specific.

Topics: Acyl-CoA Dehydrogenase; Animals; Blood Pressure; Cardiomegaly; Fenofibrate; Gene Expression; Hypertension; Ligands; Male; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; PPAR alpha; Procollagen; Rats, Inbred SHR

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC)=0.873) and TGF-β (AUC=0.878). On the basis of ROC curve analysis we found that CT-1>152 pg/mL, TGF-β<7.7 ng/mL, syndecan>2.3 ng/mL, NT-proBNP>332.5 pg/mL, CysC>1 mg/L and NGAL>39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF-NT-proBNP, TGF-β, CT-1, CysC-compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.

Topics: Acute-Phase Proteins; Aged; Biomarkers; Cystatin C; Cytokines; Female; Galectin 3; Heart Failure; Humans; Hypertension; Lipocalin-2; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Protein Precursors; Proto-Oncogene Proteins; Receptors, Interleukin-1 Type I; Syndecan-4; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking.. We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP.. African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population.

Topics: Atherosclerosis; Black or African American; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Residence Characteristics; Risk Factors; White People

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood.

Topics: Age of Onset; Animals; Compliance; Death, Sudden, Cardiac; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Gene Knockout Techniques; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Glomerulus; Long QT Syndrome; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Phenotype; Rats; Rats, Inbred Dahl; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Signal Transduction

The purpose of this study was to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels differ according to race/ethnicity.. Natriuretic peptides (NP) are hormones with natriuretic, diuretic, and vasodilatory effects. Experimental NP deficiency promotes salt-sensitive hypertension and cardiac hypertrophy, conditions that are more common among black individuals.. We examined plasma NT-proBNP levels according to race/ethnicity in 3,148 individuals (51% black, 31% white, 18% Hispanic) free of prevalent cardiovascular disease in the Dallas Heart Study. NT-proBNP values in the bottom sex-specific quartile were defined as low. Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates and magnetic resonance imaging measurements of cardiac structure and function.. Hypertension was present in 41%, 25%, and 16% of black, white, and Hispanic individuals, respectively. Unadjusted NT-proBNP levels were lowest in black (median: 24 pg/ml; interquartile range [IQR]: 10 to 52 pg/ml) as compared with Hispanic (30 pg/ml; IQR: 14 to 59 pg/ml) and white individuals (32 pg/ml; IQR: 16 to 62 pg/ml), p < 0.0001. In multivariable-adjusted models, black individuals still had significantly lower NT-proBNP levels (-39% [95% confidence interval: -46% to -31%]; p < 0.0001) and greater odds of having low NT-proBNP (odds ratio: 2.46 [95% confidence interval: 1.86 to 3.26]), compared with white individuals. In contrast, NT-proBNP levels did not significantly differ between Hispanic and white individuals (p = 0.28). The finding of lower NT-proBNP levels in black individuals was similar when analyses were restricted to healthy participants without cardiovascular risk factors.. In this multiethnic cohort, NT-proBNP levels differ substantially according to race/ethnicity. Despite a higher prevalence of hypertension, black individuals had significantly lower NP levels than white and Hispanic individuals. A relative NP "deficiency" among black individuals may lead to greater susceptibility to salt retention and hypertension.

Topics: Adult; Black or African American; Female; Healthy Volunteers; Hispanic or Latino; Humans; Hypertension; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; White People

Runners with exercise-induced high blood pressure have recently been reported to exhibit higher levels of cardiac markers, vasoconstrictors, and inflammation. The authors attempted to identify correlations between exercise-related personal characteristics and the levels of biochemical/cardiac markers in marathon runners in this study. Forty healthy runners were enrolled. Blood samples were taken both before and after finishing a full marathon. The change in each cardiac/biochemical marker over the course of the marathon was determined. All markers were significantly (P<.001) increased immediately after the marathon (creatine kinase-MB [CK-MB]: 7.9 ± 2.7 ng/mL, cardiac troponin I (cTnI): 0.06 ± 0.10 ng/mL, N-terminal pro-B-type natriuretic peptide (NT-proBNP): 95.7 ± 76.4, endothelin-1: 2.7 ± 1.16, high-sensitivity C-reactive protein [hs-CRP]: 0.1 ± 0.09, creatine kinase [CK]: 315.7 ± 94.0, lactate dehydrogenase [LDH]: 552.8 ± 130.3) compared with their premarathon values (CK-MB: 4.3 ± 1.3, cTnI: 0.01 ± 0.003, NT-proBNP: 27.6 ± 31.1, endothelin-1: 1.11 ± 0.5, hs-CRP: 0.06 ± 0.07, CK: 149.2 ± 66.0, LDH: 399 ± 75.1). In middle-aged marathon runners, factors related to increased blood pressure were correlated with marathon-induced increases in cTnI, NT-proBNP, endothelin-1, and hs-CRP. These correlations were observed independent of running history, records of finishing, and peak oxygen uptake.

Topics: Biomarkers; Blood Pressure; Blood Pressure Determination; C-Reactive Protein; Creatine Kinase; Endothelin-1; Heart; Humans; Hypertension; L-Lactate Dehydrogenase; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Running; Troponin I; Troponin T

Left-ventricular hypertrophy and interstitial fibrosis are the main pathophysiological factors of heart failure with preserved ejection fraction. Blockade of the serotonin 5-HT2B receptor (5-HT2BR) has been shown to reduce cardiac hypertrophy, oxidative stress, and extracellular cell matrix activation. In this study, we evaluated the effects of the 5-HT2BR blockade, on hemodynamic and cardiac remodeling, in spontaneously hypertensive rats (SHRs) that display a diastolic dysfunction with preserved ejection fraction.. Thirty-seven-week-old SHRs were randomized in four groups receiving either saline, the selective 5-HT2BR antagonist RS-127445 (1 mg/kg per day), a calcium channel blocker nicardipine (6 mg/kg per day), or RS-127445 + nicardipine. During the 14 weeks of treatment period, cardiac function and blood pressure were monitored by echocardiography and tail-cuff. Finally, electrocardiograms and invasive hemodynamics were obtained before blood collection. Heart was analyzed for morphology and mRNA expression. A complementary study evaluated the cardiac and vascular effects of serotonin on wild-type and mice knockout for the 5-HT2BR (Htr2B) and/or the 5-HT2AR (Htr2A).. Despite the left ventricular 5-HT2BR overexpression, 5-HT2BR blockade by RS-127445 did not affect left ventricular hypertrophy and fibrosis in SHRs. This antagonist did not improve diastolic dysfunction, neither alone nor in combination with nicardipine, although it induced plasma brain natriuretic peptide decrease. Moreover, RS-127445 amplified subendocardial fibrosis and favored left ventricular dilatation. Finally, a subendocardial left ventricular fibrosis was induced by chronic serotonin in wild-type mice, which was increased in Htr2B animals, but prevented in Htr2A and Htr2A/2B mice, and could be explained by a contribution of the endothelial 5-HT2BRs to coronary vasodilatation.. This work is the first to identify a cardioprotective function of the 5-HT2BR in an integrated model of diastolic dysfunction with preserved ejection fraction.

Topics: Animals; Blood Pressure; Echocardiography; Heart Failure; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Male; Mice; Mice, Knockout; Natriuretic Peptide, Brain; Pyrimidines; Rats; Rats, Inbred SHR; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Serotonin; Serotonin Antagonists; Ventricular Dysfunction, Left

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.. In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.. Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m(2); female > 78 g/m(2)). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).. In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiomyopathy, Hypertrophic; Case-Control Studies; Collagen; Echocardiography, Doppler; Female; Fibrosis; Humans; Hypertension; Hypertrophy, Left Ventricular; Image Interpretation, Computer-Assisted; London; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Stroke Volume; Tertiary Care Centers; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the "lowLVEF" group) and the 90 patients showing LVEF values ≥ 40% (the "highLVEF" group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = -0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84-0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.

Topics: Aged; C-Reactive Protein; Cathepsin K; Echocardiography; Extracellular Matrix; Female; Heart Failure; Humans; Hypertension; Lipoproteins; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; Troponin I; Ventricular Dysfunction, Left

Apelin is an endogenous ligand for the G protein-coupled receptor APJ. The association between apelin and cardiac modeling has been reported. However, if serum apelin affect the left ventricular hypertrophy (LVH) prevalence in hypertensive patients remains unknown.. We enrolled 344 untreated hypertensive patients. The presence of LVH was determined by echocardiography. The blood was drawn from these patients and serum apelin level was detected. To study the direct effect of apelin on cardiac hypertrophy, cardiomyocytes were cultured and were transfected with apelin gene. Morphometric analysis and measurement of protein contain per cell were then performed.. We observed a significantly lower serum apelin level in hypertensive patients with LVH compared with those without LVH. Receiver operating characteristic analyses shows that serum apelin level is robust in discriminating patients with LVH from those without. Our in vitro study showed that cellular protein content and cellular size was increased by Ang II treatment, which can be markedly inhibited by the apelin over-expression in cultured cardiomyocytes.. Our clinical date established a link between apelin and LVH, suggesting serum apelin may be used as a predicator for LVH prevalence in hypertensive patients. The direct evidence in vitro suggest apelin pathway is involved in the cardiomyocyte adaption to hypertrophic stimuli.

Topics: Adult; Angiotensin II; Animals; Apelin; Apelin Receptors; Blood Pressure; C-Reactive Protein; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Intercellular Signaling Peptides and Proteins; Ligands; Male; Middle Aged; Myocytes, Cardiac; Natriuretic Peptide, Brain; Prevalence; Rats; Receptors, G-Protein-Coupled; ROC Curve; Transfection

We investigated the association between left ventricular (LV) torsional deformation and vascular dysfunction, fibrosis, neurohumoral activation, and exercise capacity in patients with normal ejection fraction. In 320 newly-diagnosed untreated hypertensive patients and 160 controls, we measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler echocardiography; global longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw - UtwMVO ), at peak (%dpTw - UtwPEF ), and the end of early LV diastolic filling (%dpTw - UtwEDF ) by speckle tracking imaging; transforming growth factor (TGFb-1), metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloptoteinase-1(TIMP-1), markers of collagen synthesis, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Oxygen consumption (VO2 ), measured by means of cardiopulmonary exercise test, was assessed in a subset of 80 patients. The PWV, CFR, longitudinal strain and strain rate, %dpTw-UtwMVO , %dpTw-UtwPEF , and %dpTw-UtwEDF were impaired in hypertensive patients compared with controls. In multivariable analysis, CFR, PWV, LV mass, and systolic blood pressure were independent determinants of longitudinal strain, strain rate, and untwisting markers (P < 0.05). Increased TGFb-1 was related with increased collagen synthesis markers, TIMP-1 and MMP-9 and these biomarkers were associated with impaired longitudinal systolic strain rate, untwisting markers, CFR and PWV (P < 0.05). Delayed untwisting as assessed by reduced %dpTw - UtwEDF was related with increased NT-proBNP and reduced VO2 (P < 0.05).. Impaired LV untwisting is associated with increased arterial stiffness and coronary microcirculatory dysfunction, and is linked to reduced exercise capacity and neurohumoral activation in hypertensive heart disease. A fibrotic process may be the common link between vascular dysfunction and abnormal myocardial deformation.

Topics: Biomarkers; Blood Pressure; Echocardiography; Female; Heart Diseases; Heart Ventricles; Humans; Hypertension; Male; Matrix Metalloproteinase 9; Middle Aged; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta

Detecting left ventricular (LV) dysfunction at an early stage is key in addressing the heart failure epidemic. In proteome profiling experiments in mice subjected either to aortic banding or sham, the circulating CXCR3 ligands monokine induced by interferon-γ (MIG) and interferon-γ inducible protein 10 (IP10) were 5 to 40 fold up-regulated at eight weeks. We assessed the diagnostic value of circulating NT-pro BNP and CXCR3 ligands (MIG, IP10, Interferon-inducible T-cell alpha chemo-attractant [I-TAC]) in patients with hypertension (≥140/90 mm Hg) associated with subclinical (n = 19) or symptomatic (n = 16) diastolic LV dysfunction on echocardiography and healthy controls. NT-pro BNP, MIG, IP10, I-TAC all increased (p ≤ 0.014) across the categories of worsening left ventricular dysfunction. In patients with symptomatic disease, MIG, IP10, and I-TAC increased 210% (p = 0.015), 140% (p = 0.007) and 120% (p = 0.035) more than NT-pro BNP. The optimal discrimination limits, obtained by maximizing Youden's index were 246 pmol/L, 65 pg/mL, 93 pg/mL, and 24 pg/mL, respectively. The odds ratios associated with the four biomarkers were significant (p ≤ 0.010), ranging from 4.00 for IP10 to 9.69 for MIG. With adjustment for NT-pro BNP, the CXCR3 ligands retained significance (p ≤ 0.028). Adding optimized thresholds for the CXCR3 ligands to NT-pro BNP enhanced (p ≤ 0.014) the integrated discrimination improvement and the net reclassification improvement. In conclusion, congruent with the concept that inflammation plays a key role in the pathogenesis of LV dysfunction, MIG, IP10 and I-TAC add diagnostic accuracy over and beyond NT-pro BNP.

Topics: Animals; Blood Pressure; Chemokine CXCL10; Chemokine CXCL11; Chemokine CXCL9; Female; Humans; Hypertension; Inflammation; Ligands; Male; Mice; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, CXCR3; Ventricular Dysfunction, Left

The present study was designed to evaluate the antihypertensive and cardiorenal protective effects of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, in Dahl salt-sensitive hypertensive rats (DS rats), and to compare the effects with spironolactone and eplerenone. DS rats were fed a control diet (0.3% NaCl) or high salt diet (8% NaCl) from 7 weeks of age. CS-3150 (0.25-2mg/kg), spironolactone (10-100mg/kg) or eplerenone (10-100mg/kg) were orally administered once a day to DS rats fed a high salt diet for 7 weeks. The high salt diet significantly increased systolic blood pressure, which was prevented by treatment with CS-3150 in a dose-dependent manner with no hyperkalemia (>5.5mEq/L). The antihypertensive effect of CS-3150 (0.5mg/kg) was equivalent to that of spironolactone (100mg/kg) and eplerenone (100mg/kg). CS-3150 also suppressed proteinuria and renal hypertrophy induced by the high salt diet. Histopathological examination of kidneys showed that CS-3150 markedly ameliorated glomerulosclerosis, tubular injury and tubulointerstitial fibrosis. In addition, CS-3150 inhibited left ventricular hypertrophy and elevation of plasma brain natriuretic peptide level. In contrast, the cardiorenal protective effects of spironolactone or eplerenone were partial, and the dose-dependency was not clear, especially in eplerenone-treated rats. These results indicate that chronic treatment with CS-3150 exerts antihypertensive and cardiorenal protective effects in a DS hypertensive rat model, and its potency is much superior to that of spironolactone or eplerenone. Thus, CS-3150 could be a promising agent for the treatment of hypertension and cardiorenal disorders.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cytoprotection; Heart; Hypertension; Kidney; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Organ Size; Potassium; Pyrroles; Rats; Rats, Inbred Dahl; Receptors, Mineralocorticoid; Safety; Sulfones

To distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on a morphological examination is often challenging. Growth differentiation factor 15 (GDF-15) is a novel diagnostic and prognostic biomarker for several cardiovascular diseases. In patients with LVH, GDF-15 promises to be a useful biomarker to distinguish between HCM and H-LVH. We evaluated 93 patients with H-LVH, 28 with HCM, and 28 disease control individuals. Serum GDF-15 concentrations were measured with an enzyme-linked immunosorbent assay. Circulating GDF-15 levels were significantly higher in patients with H-LVH than with HCM (P = 0.003). On the other hand, values for plasma B-type natriuretic peptide (BNP) levels were significantly lower in patients with H-LVH than with HCM (P = 0.004). Serum GDF-15 and plasma BNP levels positively correlated in patients with H-LVH but not with HCM. Multivariate logistic regression analysis revealed GDF-15 (odds ratio 12.06, confidence interval 1.85-78.77, P < 0.01) as an independent predictor of H-LVH among patients with LVH. In receiver-operating characteristic analysis, GDF-15 achieved an area under the curve of 0.70 for the identification of H-LVH. We found that GDF-15 might be a useful biomarker for discriminating HCM from H-LVH. Understanding serum GDF-15 values may have clinical utility for patients with LVH because the therapeutic strategies for treating HCM and H-LVH differ.

Topics: Aged; Area Under Curve; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diagnosis, Differential; Female; Growth Differentiation Factor 15; Humans; Hypertension; Hypertrophy, Left Ventricular; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Prognosis; ROC Curve

N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts cardiovascular events and mortality in hypertensive patients. Relationship between NT-proBNP level and left ventricular (LV) hypertrophy is well known in hypertensive patients. However, the studies investigating relationship between LV geometric patterns and serum NT-proBNP level have conflicting results and are in a limited number. The goal of the present study is to investigate relation between NT-proBNP and abnormal LV geometric patterns in untreated hypertensive patients. Measurements were obtained from 273 patients with untreated essential hypertension (mean age = 51.7 ± 5.8 years) and 44 healthy control subjects (mean age; 51.3 ± 4.7). Four different geometric patterns (NG: normal geometry; CR: concentric remodelling; EH: eccentric hypertrophy; CH: concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness. NT-proBNP and other biochemical markers were measured in all subjects. The highest NT-proBNP levels were determined in the CH group compared with the control group and other geometric patterns (p < 0.05). NT-proBNP levels of all geometric patterns were higher than the control group (p < 0.05, for all). NT-proBNP levels were similar between CR and NG groups (p > 0.05). NT-proBNP was independently associated with LV geometry (β = 0.304, p = 0.003) and LVMI (β = 0.266, p = 0.007) in multiple linear regression analysis. Serum NT-proBNP level was independently associated with LVMI and LV geometry in untreated hypertensive patients with preserved ejection fraction.

Topics: Adult; Aged; Biomarkers; Essential Hypertension; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Ventricular Function, Left

N-terminal pro-brain natriuretic peptide (NT-proBNP) is an excellent biomarker to diagnose left ventricular (LV) dysfunction. LV myocardial performance index (MPI-Tei index) is commonly used as a measure of combined systolic and diastolic function. We aimed to investigate the relationship between NT-proBNP and tissue Doppler derived MPI in newly diagnosed hypertensive patients with preserved LV ejection fraction (LVEF). We studied 236 patients with newly diagnosed HT (mean age; 52.9 ± 5.2 years). Echocardiographic examination was performed in all patients. LV mass index (LVMI) was calculated. Conventional Doppler indices (E and A waves) were recorded. The MPI value was obtained from the tissue Doppler derived ejection time, isovolumic contraction and relaxation times. The patients were divided into two groups according to the median NT-proBNP value (NT-proBNPlow group <114 pg/ml and NT-proBNPhigh group ≥114 pg/ml). Patients with NT-proBNPhigh were older and had higher levels of glucose and creatinine, lower E/A ratio and higher LVMI and MPI values than patients with NT-proBNPlow. However, LVEF were similar among the groups. Multiple linear regression analysis showed that NT-proBNP was independently associated with age, LVMI, MPI and E/A ratio. Increased NT-proBNP level was independently associated with impaired myocardial performance index in newly diagnosed hypertensive patients with preserved LVEF.

Topics: Adult; Aged; Biomarkers; Echocardiography, Doppler; Female; Heart; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left; Ventricular Function, Left

Primary aldosteronism (PA) is the most frequent form of secondary hypertension, but diagnostic tools for this disease still lack optimal accuracy. The heart is one important target tissue for damage due to excess aldosterone, and the role of natriuretic peptides is well recognized in diagnosing heart failure. We hypothesized that measuring the NT-proBNP could improve the diagnostic evaluation of PA. We enrolled 132 hypertensive patients, who underwent aldosterone to renin ratio (ARR) screening, and 81 underwent an intravenous saline loading test (ivSLT) because of a high ARR. The NT-proBNP level positively correlated with the ARR and inversely correlated with the renin level. The NT-proBNP level was higher in patients with a high ARR than in those with a low ARR and higher in patients with a positive ivSLT than in those with a negative ivSLT. After logistic regression analysis, an NT-proBNP value above the median and male gender were predictors of a positive ivSLT. The proportion of patients with a positive ivSLT ranged from only 23 % in females with a low NT-proBNP to 93 % in males with a high NT-proBNP. NT-proBNP and gender are predictors of a positive PA confirmatory test. These findings highlight the possibility of using NT-proBNP to identify which patients with a high ARR should receive a complete PA diagnostic evaluation.

Topics: Adult; Aldosterone; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Renin; Sex Factors; Sodium Chloride

The aim of this study was to compare the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP), electrocardiographic (ECG) criteria and transthoracic echocardiography (TTE) versus cardiac magnetic resonance imaging in detecting left ventricular hypertrophy (LVH). The study included 42 hypertensive subjects with mean±s.d. age 48.1±12.3 years, 57.1% men, 24-h ambulatory blood pressure 144/89 mm Hg, left ventricular ejection fraction >50%, without symptoms of heart failure, and not taking any drugs that interfere with hormonal regulation. The accuracies of the methods in detecting LVH were compared at two diagnostic LVH cutoffs: low, 83 g m(-2) in men and 67 g m(-2) in women; and high, 96 g m(-2) in men and 81 g m(-2) in women. With the low and high LVH cutoffs, the areas under the receiver-operating characteristic curves and the optimal values for NT-proBNP were 0.761, 0.849, 200 and 421 pg ml(-1), respectively. An NT-proBNP level under 30 pg ml(-1) ruled out LVH with 100% sensitivity. The optimal values and literature-based values of NT-proBNP allowed a correct classification of 73-81% of the subjects. In 80-90% of the cases, the diagnostic accuracy of NT-proBNP was close to that of ECG criteria but lower than that of TTE criteria. Interestingly, combining ECG criteria and NT-proBNP level improved the diagnostic performance to be at least comparable to that of TTE: the percentages of correctly classified subjects were 73-95% vs. 67-86%, respectively. Of note, the range considers both diagnostic LVH cutoffs. The simultaneous use of ECG criteria and NT-proBNP plasma levels seemed to be powerful enough to detect LVH in most hypertensive subjects.

Topics: Adult; Blood Pressure Monitoring, Ambulatory; Echocardiography; Electrocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity

Blood pressure control is closely related to target organ damage in elderly patients with hypertension. The aim of this study was to determine the relationship between ambulatory blood pressure monitoring (ABPM) indices and cardiac damage in elderly male patients with treated essential hypertension (EH).. This study included 998 Chinese men (mean age, 78.44 ± 12.02 years) with EH. Participants underwent cardiac function assessment, laboratory testing, and ABPM, including ABP, BP variability, BP circadian rhythms, and hypertensive or hypotensive time indices. The relationships between ABPM indices and cardiac damage (expressed by shape and function) were assessed using ridge regression analysis.. Ridge regression analysis revealed the following after adjustments for age, common cardiovascular risk factors, disease, and medications: N-terminal fragment pro-B-type natriuretic peptide was negatively correlated with the diastolic blood pressure nocturnal fall rate; the peak early/atrial velocity (E/A) ratio E/A ratio was negatively correlated with the 24 h mean systolic blood pressure (24 hmSBP), daytime SBP (dSBP), and nocturnal SBP (nSBP); and ejection fraction (EF) was negatively correlated with 24 h SBP percent time of elevation (24 hSBP PTE %) and 24 h DBP percent time of elevation (24 hDBP PTE %). Left ventricular mass (LVM) was positively correlated with the 24 hmSBP, dSBP, nSBP, 24 h mean pulse pressure (24 hmPP), day mean pulse pressure, and nocturnal mean arterial pressure, whereas LVM was negatively correlated with the NDBPF.. Our study showed that the ABPM indices associated with cardiac damage may be regarded as an early predictive marker for cardiac function impairment in elderly male patients with EH.

Topics: Aged; Aged, 80 and over; Asian People; Blood Pressure; Blood Pressure Monitoring, Ambulatory; China; Circadian Rhythm; Cross-Sectional Studies; Essential Hypertension; Heart; Heart Function Tests; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Stroke Volume

Karolinska Rennes (KaRen) is a prospective observational study to characterize heart failure patients with preserved ejection fraction (HFpEF) and to identify prognostic factors for long-term mortality and morbidity.. To report characteristics and echocardiography at entry and after 4-8 weeks of follow-up.. Patients were included following an acute heart failure presentation with B-type natriuretic peptide (BNP)>100 ng/L or N-terminal pro-BNP (NT-proBNP)>300 ng/L and left ventricular ejection fraction (LVEF)>45%.. The mean ± SD age of 539 included patients was 77 ± 9 years and 56% were women. Patient history included hypertension (78%), atrial tachyarrhythmia (44%), prior heart failure (40%) and anemia (37%), but left bundle branch block was rare (3.8%). Median NT-proBNP was 2448 ng/L (n=438), and median BNP 429 ng/L (n=101). Overall, 101 patients did not return for the follow-up visit, including 13 patients who died (2.4%). Apart from older age (80 ± 9 vs. 76 ± 9 years; P=0.006), there were no significant differences in baseline characteristics between patients who did and did not return for follow-up. Mean LVEF was lower at entry than follow-up (56% vs. 62%; P<0.001). At follow-up, mean E/e' was 12.9 ± 6.1, left atrial volume index 49.4±17.8mL/m(2). Mean global left ventricular longitudinal strain was -14.6 ± 3.9%; LV mass index was 126.6 ± 36.2g/m(2).. Patients in KaRen were old with slight female dominance and hypertension as the most prevalent etiological factor. LVEF was preserved, but with increased LV mass and depressed LV diastolic and longitudinal systolic functions. Few patients had signs of electrical dyssynchrony (ClinicalTrials.gov.- NCT00774709).

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Comorbidity; Echocardiography; Electrocardiography; Female; France; Heart Failure; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Prospective Studies; Registries; Risk Factors; Sex Factors; Stroke Volume; Sweden; Time Factors; Ventricular Function, Left

Few reports have examined the utility of plasma B-type natriuretic peptide (BNP) testing for cardiovascular (CV) risk stratification in real-world hypertensive subjects. Subjects of the study were community-based hypertensive patients (n = 5,865). The CV event rate within each BNP quartile was estimated, and a Cox regression model was used to determine the relative hazard ratio (HR) among the quartiles. Furthermore, to determine the usefulness of BNP as a biomarker in combination with the Framingham risk score (FRS), the predictive abilities in terms of area under the curve of receiver operating characteristic analysis, net reclassification improvement, and integrated discrimination improvement indices were determined. The mean follow-up duration was 5.6 years. The highest quartile showed a significantly higher rate of CV events compared with the lower quartiles (p <0.001). After adjustment for established CV risk factors, the HR for CV events increased significantly according to the quartile (p value for trend <0.03), and the HR for the highest quartile was significantly elevated compared with the lowest quartile (HR 1.59, 95% confidence interval 1.16 to 2.19). The predictive abilities of BNP in terms of sensitivity and specificity for CV events were comparable with those of FRS. When BNP was added to an FRS-only model, the predictive abilities in terms of area under receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement were significantly increased (all; p <0.001). Elevated BNP levels are thus a useful biomarker for CV risk stratification in unselected real-world hypertensive subjects. Adding BNP to an established CV risk score improves the predictive ability in this cohort.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cohort Studies; Follow-Up Studies; Humans; Hypertension; Japan; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Assessment; ROC Curve; Survival Analysis

Soluble ST2 is a biomarker of cardiomyocyte stretch that is useful in the diagnosis and prognosis of coronary artery disease. Its role in the field of hypertension and hypertensive heart failure (HHF) has not yet been well investigated. We studied the effect of left ventricular remodelling on the concentration of soluble ST2 in a cohort of 210 subjects with hypertension (HT). Left ventricular hypertrophy (LVH) was considered present when echocardiographic left ventricular mass indexed for height in metres (m) was greater than 46.2 g m(-1 2.7) in women and 49.2 g m(-1 2.7) in men. Subjects were subdivided into three groups: those without LVH (HT, n = 83); those with LVH (hypertension with left ventricular hypertrophy (HTLVH), n = 50) and those with HHF, n=77). Plasma ST2 and NT-pro BNP were measured using electrochemiluminescence type immunoassay. Subjects with HHF had higher plasma ST2 concentrations compared to HTLVH (134.7 ± 57.3 ng ml(-1) versus 23.0 ± 8.3 ng ml(-1), P < 0.001) and those with HT (134.7 ± 57.3 ng ml(-1) versus 14.5 ± 4.9 ng ml(-1), P < 0.0001). NT-pro BNP levels were similar when HTLVH was compared with HT (P = 0.68), but subjects with HHF had significantly higher NT-pro BNP compared to HTLVH (P < 0.0002). Soluble ST2 had strong correlation with clinical and echocardiograhic parameters, and correlated well with NT-pro BNP (r = 0.41, P < 0.0001). Plasma ST2 is a useful biomarker in not only differentiating HHF from HT with or without LVH, but also distinguishes hypertensive LVH from HT without LVH.

Topics: Adult; Aged; Cohort Studies; Echocardiography; Humans; Hypertension; Hypertrophy, Left Ventricular; Interleukin-1 Receptor-Like 1 Protein; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptors, Cell Surface; Ventricular Remodeling

We assessed the prognostic implications of low triiodothyronine (T3) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in critically ill patients with acute heart failure. We acquired data for 144 critical care patients with acute decompensated heart failure, of which 106 were included in this study. Plasma thyroid hormones and NT-proBNP levels were determined within 48 hours of admission. We assessed these measures for predicting all-cause and cardiac mortalities. At a mean follow-up period of 25 ± 31 months, the all-cause mortality rate was 51% (54 of 106) and the cardiac mortality rate was 70% (38 of 54). A multivariate Cox regression model showed that log-transformed NT-proBNP levels (log NT-proBNP; hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.38 to 6.08, p = 0.005) and T3 levels (HR 0.98, 95% CI 0.96 to 0.99, p = 0.008) were associated with all-cause mortality, and log NT-proBNP (HR 3.70, 95% CI 1.28 to 10.71, p = 0.02) and T3 (HR 0.98, 95% CI 0.96 to 0.99, p = 0.01) were associated with cardiac mortality. Based on cut-off values for NT-proBNP (10,685 pg/ml) and T3 (52.3 ng/dl), Kaplan-Meier analyses provided significant prognostic information with the highest risk for all-cause mortality in the low T3 (≤52.3 ng/dl)/high NT-proBNP (>10,685 pg/ml) group (HR 8.54, 95% CI 4.19 to 17.40, p <0.0001). In conclusion, T3 levels appear to be independent predictors for both all-cause and cardiac mortalities among critical ill patients with heart failure, and high NT-proBNP and low T3 levels predict a worse long-term outcome.

Topics: Aged; Aged, 80 and over; Comorbidity; Coronary Artery Disease; Critical Illness; Diabetic Angiopathies; Euthyroid Sick Syndromes; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Regression Analysis; ROC Curve; Survivors; Triiodothyronine

Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems.

Topics: Acromegaly; Angiotensin-Converting Enzyme 2; Animals; Blood Pressure; Body Composition; Body Weight; Cattle; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Glucose; Glucose Tolerance Test; Growth Hormone; Homeostasis; Hypertension; Insulin; Kidney Glomerulus; Male; Mice; Mice, Transgenic; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Renin-Angiotensin System; Systole; Time Factors

Even a slight decrease in the glomerular filtration rate (GFR) is an independent risk factor for cardiovascular disease. Arterial stiffness, left ventricular hypertrophy and N-terminal pro-brain natriuretic peptide (NT-proBNP) are independent risk factors for cardiovascular disease, which are particularly common in end-stage renal disease. We aimed to evaluate the association between GFR with arterial stiffness, left ventricle mass (LVM) and NT-proBNP in hypertensive subjects with normal to mildly impaired renal function. The study population consisted of 285 newly diagnosed hypertensive patients (mean age; 49.9 ± 11.8 years). GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Pulse wave velocity (PWV) and augmentation index (AIx), which reflects arterial stiffness, were calculated using the single-point method via the Mobil-O-Graph® ARCsolver algorithm. LVM was obtained by echocardiography. Plasma NT-proBNP was measured by electrochemiluminescence. The patients were divided into two groups according to the median eGFR value (eGFRlow group <101 ml/min/1.73 m(2) and eGFRhigh group ≥ 101 ml/min/1.73 m(2)). LVM and NT-proBNP values were higher in eGFRlow group compared with eGFRhigh group (p<0.05). Pulse wave velocity and augmentation index values were higher in eGFRlow group compared with eGFRhigh group (p<0.05, for all). Multiple linear regression analysis showed that eGFR was independently associated with PWV (β=-0.422, p<0.001) and NT-proBNP (β=-0.404, p<0.001). Present study showed that eGFR was independently associated with PWV and NT-proBNP values. Importantly, these findings may explain, in part, the increase in cardiovascular risk in with slightly impaired renal function.

Topics: Adult; Algorithms; Cardiovascular Diseases; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Regression Analysis; Risk Factors; Vascular Stiffness

Kidney function and cardiovascular disease are closely connected and albuminuria is a proven marker of cardiovascular risk. The present study investigated the prevalence and characteristics of albuminuria in patients with hypertension. Outpatients with essential hypertension under medical treatment were enrolled in this study (n = 350, 70.0 ± 11.4 years old). Urine samples were collected for the measurement of albumin concentration, which are expressed as the ratio of urine albumin to creatinine concentration (mg/g Cr). Cross-sectional analyses were also performed of the relationships between urinary albumin and other variables. Urinary albumin was detected in 88.3% of patients, while only 35.4% showed abnormal albuminuria (≥30 mg/g Cr). The presence of abnormal albuminuria was independently correlated with systolic blood pressure, B-type natriuretic peptide, and C-reactive protein by multivariate analysis (P < 0.05). Furthermore, multivariate regression analysis identified systolic blood pressure, serum creatinine, B-type natriuretic peptide, and C-reactive protein as the only factors showing independent correlation with urinary albumin (P < 0.05). Thus, approximately 35% of hypertensive patients had abnormal albuminuria. Urinary albumin was closely associated with blood pressure, C-reactive protein, and B-type natriuretic peptide, indicating that the severity of albuminuria parallels that of systemic inflammation, cardiac load, and blood pressure.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Albuminuria; Biomarkers; Blood Pressure; C-Reactive Protein; Creatinine; Cross-Sectional Studies; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Insufficiency; Risk Factors; Young Adult

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community.. NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.. DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.. Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.. A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Topics: Aged; Amino Acid Substitution; Atrial Natriuretic Factor; Diastole; Echocardiography, Doppler; Female; Gene Frequency; Genotype; Heart; Humans; Hypertension; Linear Models; Logistic Models; Male; Middle Aged; Minnesota; Multivariate Analysis; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Prevalence; Receptors, Atrial Natriuretic Factor; Ventricular Dysfunction, Left

Several guidelines recommend that home blood pressure (HBP) be measured both in the morning and in the evening. However, there have been fewer reports about the clinical significance of morning HBP than about the clinical significance of evening HBP.. Our study included 4,310 patients recruited for the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We measured morning and evening HBP, urinary albumin-creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima media thickness (IMT), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (Hs-cTnT).. The correlation coefficients for the associations between morning systolic BP (SBP) and log-transformed baPWV, NT-proBNP, or Hs-cTnT were significantly greater than the corresponding relationships for evening SBP (all P < 0.01). The goodness-of-fit of the associations between morning home SBP and UACR (P < 0.05) or baPWV (P < 0.01) was improved by adding evening home SBP to the SBP measurement. In contrast, the goodness-of-fit values of the associations between evening SBP and UACR (P < 0.001), LVMI (P < 0.05), baPWV (P < 0.001), NT-proBNP (P < 0.001), and Hs-cTnT (P < 0.001) were improved by adding morning home SBP to the SBP measurement.. Morning BP and evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted the stand-alone predictive ability of morning BP.

Topics: Aged; Albuminuria; Ankle Brachial Index; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Carotid Intima-Media Thickness; Circadian Rhythm; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Topics: Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment

A fall in blood pressure is the most common complication of outpatient hemodialysis. Several factors have been implicated, including serum sodium to dialysate gradient, ultrafiltration rate, and the amount of fluid to be removed during dialysis.. We prospectively audited 400 adult patients attending for their routine midweek hemodialysis session, and recorded changes in mean arterial blood pressure (MAP).. Mean age 58.4 ± 16.6 years, 60.9% male, 30.7% diabetic, 36.8% Caucasoid, single pool Kt/V 1.57 ± 0.4, and median percentage change in MAP -6.7% (-14.1 to + 2.8). The percentage fall in MAP was greatest for those starting with higher MAPs (β 0.448 , F 67.5, p<0.001), greater serum sodium to dialysate sodium gradient (β 0.676, F 5.59, p = 0.019), and age (β 0.163, F 5.15, p = 0.024). In addition, the percentage fall in MAP was greater in those with the lowest segmental extracellular water/total body water (ECW/TBW) ratios in the right arm prior to dialysis (β -477.5, F 7.11, p = 0.008).. Falls in blood pressure are common during dialysis, and greater for those starting dialysis with the highest systolic pressures, greater dialysate to serum sodium concentration gradient, and also those with the least ECW in the arm. As such, segmental bioimpedance may be useful in highlighting patients at greatest risk for a fall in blood pressure with dialysis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Blood Pressure Determination; Dialysis Solutions; Electric Impedance; Female; Hemoglobins; Humans; Hypertension; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Retrospective Studies; Serum Albumin; Sodium; Water-Electrolyte Imbalance

Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling.. Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured. sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters.. Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.

Topics: Adult; Angiotensin-Converting Enzyme 2; Biomarkers; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptidyl-Dipeptidase A; Renin-Angiotensin System; Stroke Volume; Systole; Ultrasonography; Ventricular Remodeling

To evaluate the switching from an angiotensin receptor blocker (ARB) to a drug combination containing an ARB and a diuretic drug in terms of effects on hypertension, cardiac load, and cardiac function.. In a study conducted on 82 patients with a history of heart failure and hypertension who had been treated with an ARB but failed to reach the target blood pressure, ongoing oral ARB treatment was switched to a drug combination of losartan and hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM), the variations in blood pressure and the effects on cardiac load and cardiac function were evaluated before and after treatment.. Comparison of the ABPM findings before and after switching treatment showed significant improvements in mean systolic and diastolic blood pressure, improvements in systolic and diastolic blood pressure 1 hour before getting out of bed, and improvements in the plasma levels of human brain natriuretic peptide as an indicator of cardiac load.. The drug combination of losartan and hydrochlorothiazide showed a stronger antihypertensive effect than that of the conventional ARB and improved heart function.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; Blood Pressure; Diuretics; Drug Substitution; Drug Therapy, Combination; Female; Heart Failure; Heart Function Tests; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Compliance; Treatment Outcome

It has been shown that metabolic syndrome is associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. However, there is no study about the association between Nt-proBNP and metabolic syndrome in hypertensive patients.. : To elucidate the relationship between Nt-proBNP and components of metabolic syndrome in hypertensive patients.. Fasting blood samples were obtained from 74 hypertensive patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.. Forty-four hypertensive patients met the criteria for metabolic syndrome. We found that plasma Nt-proBNP levels were lower in hypertensive patients with metabolic syndrome attributable to inverse relationships between Nt-proBNP and albumin, triglyceride, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). We further performed a multivariable linear regression analysis. The result showed that HOMA-IR is the independent predictor of plasma Nt-proBNP levels in hypertensive patients.. Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in hypertensive patients. HOMA-IR is the independent predictor of Nt-proBNP in hypertensive patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Female; Homeostasis; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

Hypertension is a highly prevalent disease associated with cardiovascular morbidity and mortality. Recent studies suggest that patients with hypertension also have a deficiency of certain cardiac peptides. Previously we demonstrated that a single intravenous injection of the myocardium-tropic adeno-associated virus (AAV) 9-based vector encoding for proBNP prevented the development of hypertensive heart disease (HHD) in spontaneously hypertensive rats (SHRs). The current study was designed to determine the duration of cardiac transduction after a single AAV9 injection and to determine whether cardiac BNP overexpression can delay the progression of previously established HHD, and improve survival in aged SHRs with overt HHD.. To evaluate the duration of cardiac transduction induced by the AAV9 vector, we used four week old SHRs. Effective long-term selective cardiac transduction was determined by luciferase expression. A single intravenous administration of a luciferase-expressing AAV9 vector resulted in efficient cardiac gene delivery for up to 18-months. In aged SHRs (9-months of age), echocardiographic studies demonstrated progression of HHD in untreated controls, while AAV9-BNP vector treatment arrested the deterioration of cardiac function at six months post-injection (15-months of age). Aged SHRs with established overt HHD were further monitored to investigate survival. A single intravenous injection of the AAV9-vector encoding rat proBNP was associated with significantly prolonged survival in the treated SHRs (613?38 days, up to 669 days) compared to the untreated rats (480±69 days, up to 545 days)(p<0.05).. A single intravenous injection of AAV9 vector elicited prolonged cardiac transduction (up to 18 months post-injection). AAV9 induced cardiac BNP overexpression prevented development of congestive heart failure, and significantly prolonged the survival of aged SHRs with previously established overt HHD. These findings support the beneficial effects of chronic supplementation of BNP in a frequent and highly morbid condition such as HHD.

Topics: Adenoviridae; Animals; Genetic Therapy; Genetic Vectors; Heart Diseases; Hypertension; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Transduction, Genetic

The aim of this study was to investigate the correlation between the natriuretic peptide precursor B (NPPB) gene single nucleotide polymorphism (SNP) c.-1298 G/T and pulse pressure (PP) of the Chinese Han population and the association between genotype and clinical indicators of hypertension. Peripheral blood was collected from 180 unrelated patients with hypertension and 540 healthy volunteers (control group), and DNA was extracted to amplify the 5'-flanking region and 2 exons of the NPPB gene by polymerase chain reaction; the fragment was sequenced after purification. The clinical data of all subjects were recorded, the distribution of the NPPB gene c.-1298 G/T polymorphism was determined, and differences in clinical indicators between the two groups were evaluated. The mean arterial pressure PP, and creatinine levels were significantly higher in the hypertension group than in the control group (P<0.05), but no other clinical indicators differed between the groups. There were no significant differences in genotype frequency and distribution of the NPPB gene c.-1298 G/T polymorphism between the hypertension group and the control group (P>0.05); in the control group, the mean PP of individuals with the SNP c.-1298 GG genotype was greater than that of individuals with the GT+TT genotype (P<0.05). In conclusion, there was no significant correlation between the NPPB gene c.-1298 G/T polymorphism and the incidence of essential hypertension in the Han population; however, the PP of the SNP c.-1298 GG genotype was greater than that of the GT+TT genotype in the control group.

Topics: Aged; Blood Pressure; Essential Hypertension; Female; Genetic Association Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Promoter Regions, Genetic

Vascular diseases are the most prevalent diseases worldwide. This study intended to analyze peripheral blood miRNA levels and their correlation with NT-pro-BNP and cTN-I in patients with atherosclerosis or pre-atherosclerotic conditions to build a dynamic correlation between vascular diseases and their biomarkers. Serum NT-pro-BNP and cTN-I levels were measured by their respective ELISA kits. The miRNA levels were assayed by quantitative PCR. Unique miRNA signatures were identified for both atherosclerosis and pre-atherosclerosis. The levels of miR-92a, 126, 130a, 222, and 370 levels were decreased in the peripheral blood of pre-atherosclerotic subjects. In atherosclerosis, miR-21, 122, 130a, and 211 were significantly increased whereas miR-92a, 126, and 222 were markedly decreased. Serum levels of NT-pro-BNP and cTN-I correlated with each other and increased with the progression of atherosclerosis. Moreover, the levels of cTN-I and NT-pro-BNP were positively correlated with miR-21 and negatively correlated with miR-126. Integrating specific pattern of miRNA levels with NT-pro-BNP and/or cardiac troponin may improve the diagnosis of cardiovascular diseases.

Topics: Atherosclerosis; Biomarkers; Case-Control Studies; Chronic Disease; Diabetes Mellitus; Disease Progression; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Real-Time Polymerase Chain Reaction; ROC Curve; Troponin T

A pathological connection between the heart and kidney is well recognized as a cardiorenal syndrome, but the underlying mechanism remains undetermined. We hypothesized that this connection is attributable to central haemodynamic alterations.. In 386 patients with hypertension, the radial, carotid and femoral pressure waveforms were recorded with applanation tonometry to estimate the aortic pressure and pulse wave velocity (PWV). The plasma B-type natriuretic peptide (BNP) concentration and urinary albumin/creatinine ratio (UACR), cardiac and renal damage biomarkers, respectively, were also measured for each patient.. The BNP was correlated positively with UACR, aortic pulse pressure and PWV, but inversely with the estimated glomerular filtration rate (eGFR, P < 0.001). The aortic pulse pressure tended to more closely correlate with BNP than the brachial pulse pressure. The presence of (micro)albuminuria (UACR ≥30 mg/g) was associated with BNP elevation (≥50 pg/ml) independently of age, BMI, mean arterial pressure, eGFR and β-blocker treatment (odds ratio: 2.41; P = 0.04). However, further adjustment for the aortic pulse pressure or PWV rendered this albuminuria-BNP relationship insignificant (P = 0.25) and, instead, the aortic pulse pressure emerged as the strongest determinant of BNP elevation (odds ratio: 1.51 per 10mmHg; P = 0.001). Differently from albuminuria, lower eGFR was consistently related to higher plasma BNP, even after controlling for the aortic pressure and PWV.. Concomitant plasma BNP elevation with (micro)albuminuria can be explained by increases in aortic pulse pressure and PWV. This finding suggests that the altered central haemodynamics causes simultaneous damage/dysfunction in the heart and kidney, which could then contribute to cardiorenal syndrome in hypertension.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Creatinine; Glomerular Filtration Rate; Humans; Hypertension; Middle Aged; Natriuretic Peptide, Brain

We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension.. Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5±11.5 years, BMI 33±5kg/m(2) and ambulatory blood pressure 157±16/87±13mmHg with 4.2±1.5 anti-hypertensive treatment.. We did not observe intra-operative or early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20±15 (P<0.001) and 10±13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5±14.9mmHg (P=0.027) for SBP and of 10.5±9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4±3mm (P=0.031), Sokolow index of 3±3mm (P=0.205), Cornell voltage criterion of 9±7mm (P=0.027) and Cornell product of 1310±1104 (P=0.027).. Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe.

Topics: Aged; Biomarkers; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Denervation; Essential Hypertension; Female; Follow-Up Studies; France; Hospitals, University; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Artery; Risk Factors; Treatment Outcome

The present study investigated whether brachial and central blood pressures have differential impact on the cardiovascular system in the general population.. The study included 706 subjects (59 ± 10 years) who visited our hospital for a physical check-up. Brachial blood pressure and radial artery pressure waveforms were recorded using an automated device, and the pressure corresponding to the radial late systolic peak (SBP2) was taken as central blood pressure. The concentration of B-type natriuretic peptide and the intima-media thickness of the carotid artery were measured and a cross-sectional analysis was performed.. Brachial blood pressure was 128 ± 18/74 ± 12 (mean blood pressure, 92 ± 13) mmHg and SBP2 was 120 ± 19 mmHg. Although both brachial systolic blood pressure and SBP2 correlated with B-type natriuretic peptide in a univariate analysis, only SBP2 independently correlated with B-type natriuretic peptide after adjustment for possible factors. In contrast, brachial systolic blood pressure, but not SBP2, independently correlated with carotid artery intima-media thickness.. Central blood pressure is more closely associated with left ventricular load than brachial blood pressure, while brachial blood pressure is more strongly associated with vascular damage than central blood pressure.

Topics: Aged; Blood Pressure; Blood Pressure Determination; Brachial Artery; Carotid Arteries; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function

Topics: Albuminuria; Aorta; Blood Pressure; Cardio-Renal Syndrome; Humans; Hypertension; Natriuretic Peptide, Brain

Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1(Ser473), glycogen synthase kinase (GSK)-3β(Ser9), forkhead transcription factor (FKHR)(Ser256), mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2(Thr183-Tyr185), Akt-1(Ser473), GSK-3β(Ser9), FKHR(Ser256), and PKC ε(Ser729) and the level of Hsp90 were increased, while the activity of PKC α/βII(Thr638/641), ζ/λ(410/403) were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling.

Topics: Animals; Blood Pressure; Extracellular Signal-Regulated MAP Kinases; Forkhead Transcription Factors; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart Failure; HSP90 Heat-Shock Proteins; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Phosphorylation; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Protein Kinase C; Proto-Oncogene Proteins c-akt; Quinazolines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction

Arterial stiffness is an independent predictor for vascular diseases. Cardio-ankle vascular index (CAVI) is a new index of arterial stiffness. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong prognostic marker in advanced stage of coronary heart disease (CHD). In the present study, we investigated the relationship between CAVI and NT-proBNP in hypertension and CHD subjects. Five hundred one subjects (male/female, 209/292) from Vascular Medicine of Peking University Shougang Hospital were divided into four groups: healthy group (n = 186), hypertension group (n = 159), CHD group (n = 45), and hypertension with CHD group (n = 111). CAVI was measured using VS-1000 apparatus. Our results showed that CAVI was significantly higher in hypertension subjects with CHD than in healthy and hypertension group, respectively (8.42 ± 1.51 vs. 7.77 ± 1.19; 8.42 ± 1.51 vs. 7.92 ± 1.11; both P < .05). NT-proBNP was significantly higher in hypertension subjects with CHD than in healthy, hypertension, and CHD group, respectively (422.48 ± 761.60 vs. 174.29 ± 415.48; 422.48 ± 761.60 vs. 196.14 ± 299.16; 422.48 ± 761.60 vs. 209.66 ± 242.66; all P < .05). And after log transformation of NT-proBNP, this phenomenon also exists (2.32 ± 0.47 vs. 2.03 ± 0.40; 2.32 ± 0.47 vs. 2.09 ± 0.44; 2.32 ± 0.47 vs. 2.12 ± 0.42; all P < .05). There was positive correlation between log NT-proBNP and CAVI in the entire study group, healthy group, and nonhealthy group (r = 0.235, P < .001; r = 0.184, P = .023; r = 0.237, P < .001; respectively). Multivariate analysis showed that NT-proBNP was an independent associating factor of CAVI in all subjects (β = 0.150, P = .021). Our present study showed that CAVI and NT-proBNP were significantly higher in hypertension subjects with CHD compared with healthy and hypertension groups. There was significant correlation between NT-proBNP and CAVI, which indicates the relationship between arterial stiffness and biomarkers in vascular-related diseases.

Topics: Aged; Ankle; Biomarkers; Blood Pressure; Coronary Artery Disease; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Retrospective Studies; Vascular Stiffness

An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure.. A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients.. Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level.. An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients.

Topics: Aged; Atrial Fibrillation; Body Mass Index; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Vitamin D deficiency has been associated with cardiovascular dysfunction. We evaluated the role of the vitamin D receptor (VDR) in vascular endothelial function, a marker of cardiovascular health, at baseline and in the presence of angiotensin II, using an endothelial-specific knockout of the murine VDR gene. In the absence of endothelial VDR, acetylcholine-induced aortic relaxation was significantly impaired (maximal relaxation, endothelial-specific VDR knockout=58% versus control=73%; P<0.05). This was accompanied by a reduction in endothelial NO synthase expression and phospho-vasodilator-stimulated phosphoprotein levels in aortae from the endothelial-specific VDR knockout versus control mice. Although blood pressure levels at baseline were comparable at 12 and 24 weeks of age, the endothelial VDR knockout mice demonstrated increased sensitivity to the hypertensive effects of angiotensin II compared with control mice (after 1-week infusion: knockout=155±15 mm Hg versus control=133±7 mm Hg; P<0.01; after 2-week infusion: knockout=164±9 mm Hg versus control=152±13 mm Hg; P<0.05). By the end of 2 weeks, angiotensin II infusion-induced, hypertrophy-sensitive myocardial gene expression was higher in endothelial-specific VDR knockout mice (fold change compared with saline-infused control mice, type-A natriuretic peptide: knockout mice=3.12 versus control=1.7; P<0.05; type-B natriuretic peptide: knockout mice=4.72 versus control=2.68; P<0.05). These results suggest that endothelial VDR plays an important role in endothelial cell function and blood pressure control and imply a potential role for VDR agonists in the management of cardiovascular disease associated with endothelial dysfunction.

Topics: Acetylcholine; Angiotensin II; Animals; Aorta; Blood Pressure; Blotting, Western; Disease Models, Animal; DNA; Endothelial Cells; Endothelium, Vascular; Gene Expression Regulation; Humans; Hypertension; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Natriuretic Peptide, Brain; Rats; Receptors, Calcitriol; Vasodilation

Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome.. We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were also studied.. In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function.. Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Comorbidity; Creatinine; Cyclosporine; Erythrocyte Count; Female; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Tacrolimus

Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus.. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated.. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker.. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus.

Topics: Aged; Aged, 80 and over; Aldosterone; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Renin-Angiotensin System; Sympathetic Nervous System

Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored.. We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes.. The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th-75th IQR: 197-909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05).. 3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Echocardiography, Doppler; Echocardiography, Three-Dimensional; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function

The α2-isoform of the Na,K-ATPase (α2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system and is thought to play a critical role in the regulation of cardiovascular hemodynamics. However, the organ system/cell type expressing α2 that is required for this regulation has not been fully defined. The present study uses a heart-specific knockout of α2 to further define the tissue-specific role of α2 in the regulation of cardiovascular hemodynamics. To accomplish this, we developed a mouse model using the Cre/loxP system to generate a tissue-specific knockout of α2 in the heart using β-myosin heavy chain Cre. We have achieved a 90% knockout of α2 expression in the heart of the knockout mice. Interestingly, the heart-specific knockout mice exhibit normal basal cardiac function and systolic blood pressure, and in addition, these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice. Surprisingly, the heart-specific knockout mice display delayed onset of cardiac dysfunction compared with control mice in response to pressure overload induced by transverse aortic constriction; however, the heart-specific knockout mice deteriorated to control levels by 9 wk post-transverse aortic constriction. These results suggest that heart expression of α2 does not play a role in the regulation of basal cardiovascular function or blood pressure; however, heart expression of α2 plays a role in the hypertrophic response to pressure overload. This study further emphasizes that the tissue localization of α2 determines its unique roles in the regulation of cardiovascular function.

Topics: Adrenocorticotropic Hormone; Animals; Atrial Natriuretic Factor; Blood Pressure; Gene Knockout Techniques; Hypertension; Hypertrophy, Left Ventricular; Integrases; Mice; Mice, Knockout; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Ultrasonography; Vasoconstriction; Ventricular Dysfunction, Left

The aim of the present study was to determine the changes in cardiac makers and endothelin-1 (ET-1) in marathoners with exercise induced hypertension compared to normotensive controls before and after running a marathon. Among a total of 70 volunteers, 10 marathoners with systolic blood pressure (SBP) greater than 210 mmHg during a treadmill exercise stress test were selected as an exercise-induced hypertension group (EIH) and 10 marathoners with normal SBP were selected as a control group (CON). Blood was collected from all volunteers 2 h before and immediately after a marathon: creatinine kinase (CK), CK-MB, cardiac tropoin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and endothelin-1(ET-1). Cardiac markers, CK, CK-MB, and CK-MB/CK ratio significantly increased in both EIH and CON; significance was not observed between the groups. Significant increases were not observed in high sensitive-C reactive protein (hs-CRP) after the race nor between the groups. Significant increases in cTnI and NT-proBNP were observed after the race in both groups. In addition, EIH showed greater increase than CON after the race. In conclusion, increased vascular tone in EIH during a marathon increased blood pressure and myocardial burden which in turn increased myocardial cell membrane permeability to further increase myocardial tension to the point of cTnI release.

Topics: Adult; Biomarkers; Blood Pressure; Case-Control Studies; Cell Membrane Permeability; Endothelin-1; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Running; Troponin I

Topics: Acute Disease; Atrial Fibrillation; Cardiomegaly; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hemorrhage; Humans; Hydrostatic Pressure; Hypertension; Leukocytosis; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Sleep Apnea Syndromes; Smoking; Tomography, X-Ray Computed; Ultrasonography

To study relationships of 24-hour heart rate (HR) profile with involvement of the heart and kidney in women with arterial hypertension (AH).. We examined women (n=273) aged 40-70 years with essential 2-3 degree AH.. Blood pressure (BP) measurements (8 times in a week), electrocardiography, echocardiography, ambulatory BP monitoring, complex laboratory diagnostics.. Less than 10% HR lowering was registered in 22.7% of patients. Compared with the group with normal HR profile this group was characterized by high levels of clinical systolic and diastolic BP (SBP, DBP), mean 24-hour BP, nocturnal BP, SBP time index, as well as low levels of 24-hour SBP, HR, and HR variability. Same group had also significantly greater left atrial dimensions, and higher values of NT-proBNP and total risk according to SCORE (Systematic Coronary Risk Estimation). Correlation analysis revealed significant reverse association between 24-hour HR index which reflected circadian character of cardiac rhythm, left atrial dimension (r=-0.212) and NT-proBNP (r=-0.346). Flat HR profile was not statistically significant for detection of cardiac pathology (odds ratio 1.19; 95% confidence interval from 0.67 to 2.14).. Insufficient nocturnal HR lowering in women with AH was not associated with significant changes of the myocardium and kidney and clear cat links with dyslipidemia, obesity, and smoking.

Topics: Adult; Aged; Circadian Rhythm; Echocardiography; Electrocardiography, Ambulatory; Female; Heart Atria; Heart Rate; Humans; Hypertension; Kidney Function Tests; Middle Aged; Natriuretic Peptide, Brain; Organ Dysfunction Scores; Organ Size; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors

Although RAS is a relatively uncommon cause of hypertension, it is the most common form of correctable hypertension. There are clinical clues to be gained in identifying the small subset of individuals in whom directed evaluation for RAS may be useful. But its diagnostic accuracy is still poor.. The aim of the present study is to determine the usefulness of N-terminal pro-brain natriuretic peptide (NT-pro BNP) levels in helping improved diagnostic accuracy of a significant renal artery stenosis (RAS) in medically refractory hypertensive patients.. The present study included 40 patients with medical refractory hypertension in whom RAS was suspected and who were undergoing magnetic resonance angiogram (MRA) of renal artery and/or renal angiogram. Twenty consecutive patients with a significant RAS by MRA or renal angiogram (RAS group) compared with 20 consecutive patients in whom RAS was suspected but whose MRA/renal angiogram was normal or non-significant (normal group). Baseline clinical characteristics, number of antihypertensive medications before the procedure and NT-pro BNP were obtained from both groups.. Age, gender glomerular filtration rate (GFR) and LV function did not differ significantly between the two groups. NT-pro BNP level was significantly higher in RAS group (1,243 ng/ml, range 156-10,628 ng/ml) compared to normal group (129 ng/ml, range 61-3,457 ng/ml), p = 0.009. NT-proBNP level > or = 600 ng/ml has sensitivity and specificity of 80% and 95%, respectively, in diagnosis of significantRAS.. In medical refractory hypertensive patients, NT-pro BNP level increased in patients with significant RAS and was an aid in separating a significant RAS from non-significant/normal renal artery.

Topics: Biomarkers; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Artery Obstruction

B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Calcium; Cell Line, Tumor; Chemokine CCL2; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Monocytes; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor; Receptors, CCR2; rhoA GTP-Binding Protein; Signal Transduction; Time Factors

miRNAs play an important role in the pathogenesis of cardiac hypertrophy and dysfunction. However, little is known about how miR-30a regulates cardiomyocyte hypertrophy. In the study, Male C57BL/6 mice were subjected to thoracic aortic constriction, and hearts were harvested at 3 weeks. We assayed miR-30a expression level by real-time PCR and defined the molecular mechanisms of miR-30a-mediated cardiomyocyte hypertrophy. We found that myocardial expression of miR-30a was decreased in mouse models of hypertrophy and in H9c2 cells treated with phenylephrine. MiR-30a inhibition markedly increased mRNA expression of cardiac hypertrophy markers such as atrial natriuretic factor and brain natriuretic peptide in H9c2, and cell size was increased after miR-30a inhibitor treatment. Downregulated miR-30a activated autophagy by inhibiting beclin-1 expression in H9c2 cell. More important, autophagy inhibition suppressed miR-30a inhibitor-induced cardiomyocyte hypertrophy. Together, our data demonstrated that downregulated miR-30a aggravates pressure overload-induced cardiomyocyte hypertrophy by activating autophagy, thus offering a new target for the therapy of cardiomyocyte hypertrophy.

Topics: 3' Untranslated Regions; Animals; Atrial Natriuretic Factor; Autophagy; Cardiomegaly; Cell Line; Cell Size; Down-Regulation; Gene Expression Regulation; HEK293 Cells; Humans; Hypertension; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats

The multimarker approach using Luminex technology represents a new tool for studying the pathogenesis of cardiovascular disease. Although many cardiac biomarkers in heart failure have been well established, the role and significance of their measurement in hypertensive patients is still questionable. The aim of our study was to evaluate the relationship of selected biomarkers in L-NAME-induced hypertension to the left ventricular remodeling in the two different periods of hypertension development. Four groups of 3-month-old male Wistar rats were investigated: (1) control 4 (placebo for 4 weeks), (2) control 7 (placebo for 7 weeks), (3) L-NAME 4 (40 mg/kg/day for 4 weeks), and (4) L-NAME 7 (40 mg/kg/day for 7 weeks). BNP, cTnI, TNF-α, and VEGF were measured using Rat CVD Panel 1 Kit (Milliplex® MAP). Cardiac troponin T was determined using Elecsys® Troponin T high sensitive immunoassay (Roche, Switzerland). Although the systolic blood pressure increases about 50% in L-NAME-induced hypertension in rat, both hypertrophy and fibrosis were expressed only slightly in this experiment. The levels of BNP, TNF-α, or VEGF did not differ significantly among groups. However, cardiac troponin T measured by high sensitive ELISA was significantly (P<0.05) increased in L-NAME 4 (0.229 μg/l versus 0.034 μg/l) and L-NAME-7 groups (0.366 μg/l versus 0.06 μg/l) in comparison with the controls. We conclude that the slightly increased cTnT levels could indicate ischemic damage of L-NAME-hypertensive heart. Importantly, to our best knowledge, this is the first study indicating that CVD rat panel may be a useful methodological tool in experimental cardiology.

Topics: Animals; Biomarkers; Blood Pressure; Enzyme Inhibitors; Hypertension; Immunoassay; Male; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Wistar; Troponin I; Troponin T; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

The brain natriuretic peptides (BNP, NT-proBNP) are useful diagnostic markers of heart failure (HF), as exemplified by the ESC Heart Failure guidelines. The PolSenior project was an epidemiological study carried out to examine medical, psychological and socioeconomic aspects of aging in Poland. The aim of this study is an epidemiological description of HF based on elderly population from the PolSenior Study, stratified by NT-pro-BNP concentration values.. The research sample included 4979 respondents (2567 males and 2412 females) split into six equally sized age groups of elderly individuals. The study consisted of three visits performed by trained nurses and included a questionnaire survey, comprehensive geriatric assessment and blood and urine sampling with more than 50 biochemical parameters measured. Serum NT-pro-BNP was measured by electrochemiluminescence method (ECLIA).. The prevalence of chronic kidney disease (CKD) (77.8%) and atrial fibrillation (39.5%), number of hospitalizations (23.7%) and number of patients treated with HF drugs were highest in NT-proBNP > 2000 pg/ml group and least frequent in NT-proBNP < 400 pg/ml group. Obese patients had significantly more frequently NT-proBNP values < 400 pg/ml (73.0%) and less frequently NT-proBNP values >2000 pg/ml (2.8%). Age over 70 years and male gender were associated with the increased NT-pro-BNP (> 400 pg/ml) (OR 1.41; CI 1.20-1.65 for male gender).. We conclude that CKD and atrial fibrillation are associated with the occurrence of increased NT-pro-BNP, the surrogate for HF in elderly population. On the contrary, overweight or obesity is associated with lower prevalence of HF in elderly.

Topics: Aged; Aged, 80 and over; Aging; Antihypertensive Agents; Atrial Fibrillation; Biomarkers; Diabetes Mellitus; Drug Utilization; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Poland; Prevalence; Renal Insufficiency, Chronic; Sex Characteristics

Topics: Aged; Biomarkers; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Precision Medicine; Ventricular Dysfunction, Left

The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.

Topics: Antihypertensive Agents; Biomarkers; Body Water; Echocardiography; Electric Impedance; Fluid Shifts; Hemodynamics; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Volume; Renal Dialysis; Vena Cava, Inferior

In experimental heart failure animal models, remodeling of skeletal and cardiac muscle ryanodine receptors (RyR), including phosphorylation, S-nitrosylation and oxidation, have been reported to contribute to pathologic Ca2+ release, impaired muscle function and fatigue. However, it is not known whether similar remodeling of RyR1 in skeletal muscle occurs in patients with heart failure, and if this is associated with impairment of physical activity.. We studied 8 sedentary patients with New York Heart Association (NYHA) Class III heart failure and 7 age-matched, healthy, but sedentary controls. All heart failure patients had NYHA Class III and peak VO2, echocardiography and NT-proBNP data consistent with moderate to severe heart failure. The age-matched controls included were allowed hypertension but sub-clinical heart failure was to have been ruled out by normal peak VO2, echocardiography and NT-proBNP.. Exercise capacity (VO2max) differed by almost 2-fold between heart failure patients and age-matched controls. Compared with controls, skeletal muscle RyR1 in heart failure patients was excessively phosphorylated, S-nitrosylated and oxidized. Furthermore, RyR1 from heart failure patients was depleted of its stabilizing protein FK 506-binding protein 12 (FKBP12, or calstabin1).. For the first time we show that skeletal muscle RyR1 from human heart failure is post-translationally modified, which corroborates previous data from experimental animal studies. This indicates pathologic Ca2+ release as a potential mechanism behind skeletal muscle weakness and impaired exercise tolerance in patients with heart failure and suggests a potential target for pharmacologic intervention.

Topics: Aged; Biopsy; Case-Control Studies; Comorbidity; Echocardiography; Exercise Tolerance; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Ryanodine Receptor Calcium Release Channel; Severity of Illness Index

Cardiovascular mortality in primary hyperparathyroidism (PHPT) is attributed to myocardial and endothelial dysfunction. In this prospective, case-control study we assessed cardiovascular dysfunction in patients with symptomatic PHPT and its reversal after successful parathyroidectomy.. Fifty-six patients with symptomatic PHPT underwent two-dimensional echocardiography, tissue Doppler (diastolic function assessment), serum N-terminal pro-brain natriuretic peptide (s-NTproBNP, a myocardial damage marker), and endothelial- and smooth muscle-dependent vasodilatory response (vascular dysfunction) studies before, 3, and 6 months after parathyroidectomy; 25 age-matched controls were studied similarly.. Patients had greater left ventricular mass (192 ± 70 vs. 149 ± 44 g; P = .006), interventricular septal thickness (10.8 ± 2.5 vs. 9.0 ± 1.6 mm; P = .001), posterior wall thickness (9.9 ± 2.0 vs. 8.6 ± 2.2 mm; P = .004), and diastolic dysfunction (lower E/A trans-mitral flow velocity ratio [1.0 ± 0.4 vs. 1.3 ± 0.4; P = .01). Patients had greater s-NTproBNP (4,625 ± 1,130 vs. 58 ± 49 pg/mL; P = .002) and lower endothelial-mediated vasodilation (9.3 ± 8.6 vs. 11.7 ± 6.3%; P = .03) and smooth muscle-mediated vasodilation (20.1 ± 17.9 vs. 23.8 ± 11.2%; P = .01). Improvements in left ventricular mass, systolic and diastolic function, and smooth muscle-mediated vasodilation were noted from 3 to 6 months after parathyroidectomy. Endothelial-mediated vasodilation did not improve significantly. S-NTproBNP levels mirrored echocardiographic changes with a substantial, sustained decrease. Results were similar in hypertensive and normotensive patients.. Symptomatic PHPT patients have substantial cardiac and vascular dysfunction, which improve by 6 months after parathyroidectomy. Objective cardiovascular evaluation may improve outcomes in symptomatic PHPT patients.

Topics: Adult; Cardiovascular System; Case-Control Studies; Humans; Hyperparathyroidism, Primary; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Parathyroidectomy; Peptide Fragments; Prospective Studies; Ventricular Dysfunction, Left

Identification of patients with arterial hypertension and a possible onset of heart failure by determining the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) enables timely intensification of treatment and allows clinicians to prescribe and implement optimal and appropriate care. The aim of this study was to evaluate NT-proBNP in patients with longstanding hypertension and in patients with signs of hypertensive cardiomyopathy.. The study involved 3 groups, with 50 subjects each: "healthy" persons (control group), patients with hypertension and normal left ventricular systolic function (group 1) and patients with longstanding hypertension and signs of hypertensive cardiomyopathy with impaired left ventricular systolic function (group 2). We measured levels of NT-proBNP, C-reactive protein and creatinine according to the manufacturer's instructions. All the patients were clinically examined including physical examination of the heart with blood pressure, pulse rate, electrocardiogram (ECG) and echocardiogram.. Our results showed that the determined parameters generally differed significantly (Student's t-test) among the groups. The mean (+/- SD) values of NT-proBNP in the control group, group 1 and group 2 were: 2.794 (+/- 1.515) pmol/L, 9.575 (+/- 5.449) pmol/L and 204.60 (84,93) pmol/L, respectively. NT-proBNP correlated significantly with the determined parameters both in the group 1 and the group 2. In the group 1, the highest correlation was obtained with C-reactive protein (r = 0.8424). In the group 2, the highest correlation was obtained with ejection fraction (r = -0.9111). NT-proBNP showed progressive increase in proportion to the New York Heart Association (NYHA) classification. The patients in the- group 2 who belonged to the II and III NYHA class had significantly higher levels of NT-proBNP than those in the NYHA class I (ANOVA test, p = 0.001).. The obtained results suggest that NT-proBNP is a useful biomarker in the treatment of patients with longstanding hypertension who are at risk for heart failure.

Topics: Biomarkers; C-Reactive Protein; Creatinine; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Factors; Severity of Illness Index; Ventricular Dysfunction, Left

Presence of left ventricular (LV) hypertrophy significantly increases cardiovascular risk in patients suffering from hypertension. Diagnostics of LV hypertrophy in hypertensive patients is not easy and there is still no method of enabling a simple and sufficiently sensitive dia-gnosis across a large patient population. The golden standard in LV hypertrophy diagnostics is echocardiography, and there are adverse opinions regarding the use of natriuretic peptides BNP and NT proBNP (NP) to diagnose LV hypertrophy.. We examined through echocardiography 173 hypertensive patients with signs of metabolic syndrome and a moderate increase in blood pressure (130- 159/ 85- 99 mm Hg) with an average age of 54.8 ± 13.54 years, i.e. 119 men and 54 women, who were divided into 2 groups; 1 with BMI > 30 (group A with a severe obesity) and the other without obesity, BMI < 30 (group B). Both groups were examined for BNP and NT proBNP levels.. We found a positive correlation between NP and LVMi, both for BNP (r = 0.169; p = 0.033) and for NT proBNP (r = 0.240; p = 0.002). NT proBNP statistically significantly predicts the given LV hypertrophy LK in people with BMI < 30 but not in obese people (BMI > 30).. Obese patients suffer from a higher occurrence of left ventricular hypertrophy and paradoxically a lower NP value than patients with a metabolic syndrome (MS) who are not obese. Natriuretic peptides have a limited diagnostic value when assessing left ventricular hypertrophy. They are only of value in patients who are not obese and whose kidney function and systolic myocardial function have not been impaired.

Topics: Adult; Aged; Body Mass Index; Comorbidity; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Referral and Consultation

The increased prognostic accuracy of the high-sensitivity cardiac troponin T (hs-cTnT) assay vs the conventional cTnT assay has recently been reported in hypertensive patients. The authors aimed to investigate the significance of serum hs-cTnT marker for prediction of nondipper hypertension (HTN) in hypertensive patients. A total of 317 patients with newly diagnosed HTN were studied. The patients were divided into two groups: 198 dipper hypertensive patients (mean age, 51.7 ± 5.1 years) and 119 nondipper hypertensive patients (mean age, 53.4 ± 7.6 years). Hs-cTnT and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in all patients. hs-cTnT and NT-proBNP were independent predictors for nondipper HTN (P<.05 for all). The cutoff value of hs-cTnT obtained by the receiver operator curve analysis was 7.55 ng/L for the prediction of nondipper HTN (sensitivity: 79%, specificity: 70%; 95% confidence interval, 0.769-0.860; P<.001). In patients with HTN, higher serum concentration of hs-cTnT even within normal range is an independent predictor of nondipper HTN.

Topics: Biomarkers; Circadian Rhythm; Diagnosis, Differential; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Troponin T

Left ventricular (LV) hypertrophy (LVH) is classified according to geometric pattern into 4 types: concentric hypertrophy, eccentric hypertrophy, concentric remodeling, and normal geometry. Prevalence of death and cardiovascular complications associated with hypertension depend on the geometric pattern. Although soluble ST2 levels, a novel cardiac biomarker of mechanical strain is increased in hypertension, the relationship with hypertensive LV geometric patterns has not been studied. The authors investigated the relationship between soluble ST2 levels and LV geometric patterns in a cohort of hypertensive patients. LVH was considered present when echocardiographic LV mass index exceeded 49.2 g/m(2.7) in men and 46.2 g/m(2.7) in women. Patients with concentric hypertrophy had higher soluble ST2 levels compared with patients with normal geometry (20.4±8.4 ng/mL vs 14.3±5.4 ng/mL, P<.002). Therefore, soluble ST2 level is not only affected by hypertensive LV, but may be a future biomarker in differentiating concentric hypertrophy from normal geometry in hypertension.

Topics: Adult; Biomarkers; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Receptors, Cell Surface

Topics: Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Metabolic Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients.. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1.. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction.. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Topics: Adult; Aged; Arginine; Biomarkers; Diastole; Female; Humans; Hypertension; Kidney Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic

The purpose of this study was to document the incidence and extent of cardiovascular toxicity among advanced renal cell carcinoma patients treated with newer targeted cancer agents.. The potential for targeted cancer agents to induce cardiovascular toxicity has been increasingly recognized, but the overall incidence and extent of toxicity have not been well characterized. Early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.. The incidence of hypertension, left ventricular dysfunction, and heart failure was assessed for all advanced renal cell carcinoma patients treated with targeted therapies at our institution between 2004 and 2011. Grading was performed according to the Common Terminology Criteria for Adverse Events version 4.0.. Cardiovascular toxicity developed in 116 of 159 patients (73%), including 52 of 159 patients (33%) when hypertension was excluded. Toxicity varied from occurrences of asymptomatic drops in left ventricular ejection fraction to rises in N-terminal-pro-B-type natriuretic peptide to severe heart failure. The tyrosine kinase inhibitor sunitinib was the agent most frequently used, with 66 of 101 sunitinib-treated patients (65%) developing a form of cardiovascular toxicity, including 32 of 101 patients (32%), excluding hypertension. Other VEGF inhibitors such as bevacizumab, sorafenib, and pazopanib also elicited significant cardiovascular toxicity with incidences ranging from 51% to 68%.. The frequency and severity of cardiovascular toxicity in advanced renal cell carcinoma patients treated with targeted cancer therapies are high.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers; Carcinoma, Renal Cell; Cardiovascular Diseases; Female; Heart Failure; Humans; Hypertension; Kidney Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Peptide Fragments; Protein-Tyrosine Kinases; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left

To study the relationship between C-type natriuretic peptide (NT-proCNP) and other natriuretic peptides, such as pro-atrial natriuretic peptide [proANP(1-98)] and N-terminal pro-brain natriuretic peptide (NT-proBNP), in the elderly, investigating also their correlation with other traditional clinical markers of the hypertensive condition.. NT-proCNP, NT-proBNP and proANP(1-98) were measured in 57 elderly patients. They were hypertensive patients (n = 36) and normotensive controls (n = 21). Their anthropometric parameters, including Winsor's index and total and high-density lipoprotein cholesterol, were determined.. A diagnostic role of NT-proBNP in hypertensive patients was detected by a model of logistic regression, which gave a significant result [odds ratio (OR) 1.0115, P = 0.0184]. By this model the area (AUC) under the receiver-operating characteristic (ROC) curve was 0.69 ± 0.071 (P = 0.0075). On the basis of the ROC curve, the calculated serum NT-proBNP cut-off for the prediction of hypertension was greater than 164 pmol/l - the value being provided with a sensitivity of 89% coupled with a specificity of 55%. NT-proCNP and proANP(1-98) did not predict the hypertensive condition, although significant correlations were detected with serum lipid profile and creatinine levels.. By using the logistic regression analysis, NT-proBNP was identified as a significant predictor of hypertension, whereas NT-proCNP and proANP circulating levels were not shown to reliably predict the hypertensive condition. Further validation by means of larger cohort studies is undoubtedly needed to assess the use of all three peptides to increase the performance of a possible test for the prediction of the hypertensive condition in humans.

Topics: Aged; Aged, 80 and over; Anthropometry; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cholesterol; Creatinine; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Peptide Fragments; Sensitivity and Specificity

Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000-2004]) participants of the Jackson Heart Study (mean age, 47±12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005-2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0±0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage.

Topics: Adult; Aged; Black or African American; Blood Pressure; Disease Progression; Female; Humans; Hypertension; Incidence; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors

Topics: Atrial Natriuretic Factor; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain

To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension.. LV diastolic function was estimated by the ratio of early diastolic velocities (E) from transmitral inflow to early diastolic velocities (E') of tissue Doppler at mitral annulus (septal corner); NT-proBNP was measured in 207 hypertensive patients (mean age 56±14 years). The subjects were classified into 3 groups: E/E'≤10 group (n = 48), 1015 group (n = 50). The renal function was estimated by glomerular filtration rate (GFR) with (99m)Tc-DTPA. GFR from 30 to 59 ml/min/1.73 m(2) was defined as Stage 3 chronic kidney disease (CKD). GFR was also estimated using the modified MDRD equation. Albuminuria was defined by urinary albumin/creatinine ratio (UACR).. GFR was lower and UACR was higher in E/E' >15 group than in 10< E/E' ≤15 group or E/E' ≤10 group (p<0.0001), GFR was significantly negative and UACR was positive correlated with E/E' and NT-proBNP (p<0.0001). In multivariate stepwise linear analysis, GFR had significant correlation with age (p = 0.001), gender (p = 0.003), E/E' (p = 0.03), lgNT-proBNP (p = 0.001) and lgUACR (p = 0.01), while eGFR had no significant correlation with E/E' or lgNT-proBNP. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that participants in E/E'>15 group were more likely to have Stage 3 CKD compared with those in E/E'≤10 group with an adjusted odds ratio of 8.31 (p = 0.0036).. LV diastolic function, assessed with E/E' and NT-proBNP is associated with renal function in essential hypertension.

Topics: Adult; Diastole; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Factors; Ventricular Dysfunction, Left

Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease.. In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression.. Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Captopril; Disease Models, Animal; Disease Progression; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Heart Failure; Hypertension; Male; MicroRNAs; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Sodium Chloride; Treatment Outcome

Early recognition of left ventricular hypertrophy is important because antihypertensive treatment decreases morbidity and mortality. The ideal screening method for left ventricular hypertrophy in hypertensive emergency department (ED) patients has not been identified. Our objective was to determine the diagnostic accuracies of electrocardiogram (ECG) and N-terminal Pro-B-type natriuretic peptide (pro-BNP) for left ventricular hypertrophy individually and in combination in hypertensive ED patients.. Prospective diagnostic study in an academic urban tertiary care hospital ED with annual census of 65,000 visits. Inclusion criteria are as follows: adult ED patients with systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 100 mm Hg on 2 or more measurements taken 60 minutes apart. Exclusion criteria are as follows: patients with heart failure, renal insufficiency/failure, acute myocardial infarction, or without recent or scheduled echocardiograms. All patients received echocardiograms and had pro-BNP levels measured using a RAMP point-of-care device (Response Biomedical, Vancouver, BC, Canada). We calculated diagnostic test characteristics with 95% confidence intervals (CIs).. A total of 49 patients were enrolled. The average age was 57.9 years, 26.5% were male, and 63.3% were African American. Thirty-two patients (65%) had left ventricular hypertrophy by echocardiogram. Twenty-one (43%) had ECG evidence of left ventricular hypertrophy. Median pro-BNP level was 268 pg/mL. The combination of the 2 tests provided the greatest specificity (94%; 95% CI, 69%-99.7%) and positive predictive value (94%; 95% CI, (68%-99.7%).. The combination of ECG and pro-BNP is a promising screening algorithm for identification of hypertensive ED patients with left ventricular hypertrophy.

Topics: Blood Pressure; Electrocardiography; Emergency Service, Hospital; Female; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Ventricular Dysfunction, Left

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI.. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001).. Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Topics: Age Factors; Aged; Aldosterone; Angioplasty, Balloon, Coronary; Body Mass Index; Brain Ischemia; C-Reactive Protein; Coronary Artery Disease; Creatinine; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Stroke; Stroke Volume; Ventricular Function, Left

Losartan/hydrochlorothiazide (HCTZ) (Preminent®) is a fixed-dose combination of angiotensin II receptor blocker (ARB) and the thiazide diuretic HCTZ that has consistently been shown to be more effective than either losartan or HCTZ. Little is known about the relationship between losartan/HCTZ and blood levels of brain natriuretic peptide (BNP).. In this study, 44 patients with hypertension who were being treated with ARB were enrolled. The ARB was changed to losartan/HCTZ because of uncontrolled hypertension. Blood pressure (BP), pulse rate (PR), plasma levels of BNP and other biochemical parameters were analyzed at baseline and 6 and 12 months after the change from ARB. Of the total 44 patients, 33 (75%) achieved the target BP at 12 months. While there was no significant change in PR, systolic and diastolic BP were significantly reduced (-23 ± 3 mmHg and -10 ± 2 mmHg, respectively) during this period. Although there were no significant changes in biochemical parameters, plasma levels of BNP were significantly decreased, especially in patients who had higher levels of BNP at baseline, during this period.. Losartan/HCTZ therapy significantly reduced not only BP but also plasma levels of BNP in patients with hypertension. These findings suggest that losartan/HCTZ might have cardioprotective effects in patients with higher levels of BNP.

Topics: Aged; Blood Pressure; Body Weight; Diastole; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Natriuretic Peptide, Brain; Systole

Brain natriuretic peptide (BNP) has been reported to be a powerful predictor of peritoneal dialysis patient survival. However, it is unclear as to whether this is related to cardiac dysfunction or chronic volume overload.. To investigate the relationship between BNP, cardiac function and fluid volume overload, we reviewed multifrequency bioimpedance, transthoracic echocardiography and serum N-terminal probrain-type natriuretic peptide (NTproBNP) in 115 stable peritoneal dialysis outpatients attending for assessment of peritoneal dialysis and transport status.. In this cross-sectional study, the median NTproBNP was 251 (118-605) pmol/L. On simple univariate analysis, NTproBNP was associated with markers of residual renal function, volume overload, hypertension and hypertensive cardiac disease and inflammation [reduced serum albumin and raised C-reactive protein]. However, on multivariate logistical regression analysis, the strongest association for log NTproBNP was with the estimated right ventricular end-systolic pressure (β = 0.02, F = 11.5, P = 0.001), followed by log 24-h urine volume (β = -0.19, F = 10.7, P = 0.002), extracellular/total body water ratio (β = 13.5, F = 6.1, P = 0.017) and the number of different antihypertensive medications prescribed (β = 0.15, F = 8.7, P = 0.005).. In this cross-sectional study, although NTproBNP was associated with residual renal function, cardiac hypertrophy, volume overload and inflammation on simple univariate analysis, on further examination NTproBNP was predominantly affected by factors associated with volume overload, and these results require confirmation in a prospective study.

Topics: Adult; Biomarkers; Body Water; Cross-Sectional Studies; Echocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Inflammation; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Dialysis; Prognosis

Kidney donors are a chronic kidney disease (CKD) cohort virtually guaranteed to have a low risk of CKD progression, as they are screened for CKD risk factors beforehand. However, there has been no evidence of cardiovascular disease (CVD), which is an outcome of CKD, for these donors. In this study, the conditions of CKD in kidney donors were investigated and the risk of CVD was estimated using nephrectomy patients, who are thought to have a crude risk of CKD progression, as a model. In 86 kidney donors, estimated glomerular filtration rates (eGFR) were measured, and they were classified according to the CKD stage. Plasma brain natriuretic peptide (BNP) concentrations and urinary albumin (mg/g Cre) levels were also measured as markers for cardiovascular evaluation. A total of 200 nephrectomy patients were similarly classified according to the CKD stage. A multivariate regression analysis was carried out to evaluate the risk factors of CVD. Among the kidney donors, 4.9% were CKD stage 1, 24.6% stage 2 and 70.5% stage 3. Among the nephrectomy patients, 20.5% were CKD stage 2, 66.6% stage 3, 9.5% stage 4 and 3.4% stage 5. Plasma BNP concentrations of the donors were significantly higher compared to those of healthy volunteers (24.5±24.9 vs. 8.6±7.6 pg/ml, p<0.0001). In addition, approximately 16% of the donors had microalbuminuria and 4% had overt proteinuria. The prevalence of new-onset CVD was 2.3% for the donors and 10% for the nephrectomy patients (p=0.0281). By logistic regression analysis of the nephrectomy patients, proteinuria, age and hypertension were significantly independent risk factors for new-onset CVD. Our findings suggest that the risks of CVD may be increased in kidney donors. In our analysis of new-onset CVD in nephrectomy patients, proteinuria, age and hypertension were significantly related factors. This suggests that in the follow-up of kidney donors, those who present these conditions from before or during follow-up should be carefully monitored.

Topics: Adult; Age Factors; Albuminuria; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nephrectomy; Odds Ratio; Prevalence; Proteinuria; Risk Factors; Serum Albumin; Tissue Donors

Pulse pressure (an indirect measure of arterial stiffness) is a robust predictor of cardiovascular events, but its pathophysiology remains poorly understood. To gain insight into the pathophysiology of arterial stiffness we conducted an exploratory investigation of the associations of 47 circulating biomarkers in etiologic pathways of arteriosclerosis with brachial artery pulse pressure.. Participants included 1,193 African-Americans and 1,145 non-Hispanic whites belonging to hypertensive sibships. Blood pressure (BP) was measured with a random-zero sphygmomanometer. Multivariable linear regression was employed to assess the associations of biomarkers with pulse pressure after adjustment for age, sex, conventional risk factors, mean arterial pressure, heart rate, and use of aspirin, statins, estrogens, and antihypertensives. Statistical significance was set at P ≤ 0.001 (Bonferroni correction for multiple testing).. Log N-terminal probrain natriuretic peptide (NT-proBNP) (African-Americans: β = 2.11 ± 0.52, non-Hispanic whites: β = 2.65 ± 0.55), log midregional proatrial natriuretic peptide (African-Americans: β = 4.83 ± 0.70, non-Hispanic whites: β = 3.70 ± 0.67), and log osteoprotegerin (African-Americans: β = 4.64 ± 1.02, non-Hispanic whites: β = 4.19 ± 0.99) were independently associated with pulse pressure (P < 0.001 for all) in both ethnicities. Log C-reactive protein (CRP) (β = 1.56 ± 0.35), log midregional proadrenomedullin (MR-proADM) (β = 5.53 ± 1.19) and log matrix metalloproteinase-2 (β = 3.89 ± 1.06) were associated with greater pulse pressure in African-Americans only (P ≤ 0.001 for all), whereas higher fibrinogen was associated with pulse pressure in non-Hispanic whites only (β = 0.02 ± 0.004. P < 0.001).. Our results suggest that hemodynamic stress, vascular inflammation and calcification, and matrix remodeling may have a role in the pathogenesis and/or adverse consequences of increased pulse pressure.

Topics: Adrenomedullin; Aged; Arteriosclerosis; Atrial Natriuretic Factor; Biomarkers; Black People; Blood Pressure; C-Reactive Protein; Female; Fibrinogen; Humans; Hypertension; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Vascular Stiffness; White People

Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population.. This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples.. We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality.. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L(-1) and median galectin-3 was 10.9 ng mL(-1) [interquartile range (IQR) 9.0-13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL(-1) , IQR 9.1-13.4 vs. men (n = 3967) 10.7 ng mL(-1) , IQR 8.9-12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01-1.19; P = 0.036), but not CV and cancer mortality separately.. Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.

Topics: Adult; Age Factors; Aged; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Confounding Factors, Epidemiologic; Female; Fibrosis; Galectin 3; Humans; Hypertension; Kaplan-Meier Estimate; Kidney; Lipids; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neoplasms; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Sex Factors

Plasma brain natriuteric peptide (BNP) is an established marker of cardiovascular events in individuals without heart failure. Although the cardio-ankle vascular index (CAVI) is clinically used as a parameter of arterial stiffness, its usefulness for predicting cardiovascular events has not been fully examined. This study aimed to evaluate the association among CAVIs, plasma BNP levels and left ventricular (LV) hypertrophy and dysfunction in hypertensive patients.. We enrolled 136 hypertensive patients (69±10 years) who had been taking antihypertensive medications for at least one year. Echocardiography was performed to evaluate LV hypertrophy and function. Plasma BNP levels and CAVIs were also measured simultaneously.. CAVI was correlated with plasma BNP (r =0.245, p =0.004). Multiple linear regression analysis revealed three independent determinants of CAVI: age (β =0.568, p <0.001), diameter of ascending aorta (β =0.289, p <0.001), and diabetes (β =0.207, p =0.003). In addition, multiple linear regression analysis revealed two independent determinants of the plasma BNP level: left atrial diameter (β =0.334, p <0.001) and CAVI (β =0.256, p =0.002).. The present study indicates that increased CAVI is independently associated with elevated plasma BNP produced by increased LV afterload, that is, arterial stiffness, in hypertensive patients. Moreover, the present study raises the possibility that CAVI may be as useful as the plasma BNP level for predicting the risk of cardiovascular events in hypertensive patients.

Topics: Adult; Aged; Aged, 80 and over; Ankle; Ankle Brachial Index; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Vascular Resistance

Left ventricular hypertrophy (LVH) is predictive of cardiovascular disease. The vasodilator, natriuretic and diuretic actions of atrial natriuretic peptide (ANP) support a role in the pathophysiology of hypertension. Measuring the redundant precursor fragment mid-regional portion of pro-atrial natriuretic peptide (MRproANP) overcomes the technical difficulties of quantifying the bioactive ANP. This study sought to investigate the diagnostic and prognostic utility of MRproANP in a hypertensive Caucasian patient population. A total of 194 hypertensive patients (39 patients with LVH, 69±7.82 years of age, 74% female vs 155 patients without LVH, 68±6.51 years of age, 71% female) were derived from a screening study. Plasma MRproANP concentrations were quantified using immunoluminometric assays. Hypertensive patients with LVH had higher MRproANP concentrations than those without LVH (103.04 (50.58) vs 84.11 pmol l(-1) (44.82); P=0.014). Independent predictors of left ventricular mass index were LogMRproANP (P=0.022), male gender (P<0.001), body mass index (P=0.001) and history of angina or myocardial infarction (P=0.009). The receiver operating curve for MRproANP for the detection of LVH was limited, yielding an area under the curve of only 0.628 (confidence interval 0.523-0.733; P=0.014). Therefore, the role of MRproANP may not lie in the diagnosis of LVH but in monitoring the response to therapy. A nonsignificant trend towards greater mortality in patients with above-median MRproANP levels compared with below-median levels (P=0.167) was observed. Larger studies are required to assess its prognostic utility further.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Comorbidity; Confidence Intervals; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; ROC Curve; Survival Rate; White People

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension.. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study.. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value.. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Creatinine; Drug Combinations; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Hyperuricemia; Japan; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Uric Acid; Young Adult

Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment.. Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (± thiazide-diuretics).. During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P < 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P < 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P < 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. -32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P < 0.05).. HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment.

Topics: Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

This study aimed to investigate effects of a 100-km ultramarathon on cardiac markers of exercise-induced-hypertensive marathoners. 10 marathoners with exercise-induced hypertension and 10 normal marathoners participated in the study. Their blood samples were collected before starting, at 50 km, and after finishing the course (100 km). Creatinine kinase was more significantly increased in the exercise-induced-hypertensive group than in the normal group at 100 km (P<0.05). N-terminal pro-brain nutriuretic peptide was significantly increased in the exercise-induced-hypertensive group at 50 km and 10  km (P<0.05) which was significant being doubled compared to the normal group (P<0.05). Exercise-induced-hypertensive marathoners showed a significant triple-increase in C-Reactive protein at 100 km (P<0.05). In conclusion, although the exercise-induced-hypertensive runners did not have myocardial damage during the 100 km ultramarathon, they had higher myocardial stress and more damage in active muscles due to a bloodstream disability.

Topics: Adult; Biomarkers; C-Reactive Protein; Creatine Kinase; Exercise; Exercise Test; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Physical Endurance; Running

The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited.. 220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP.. This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients.

Topics: Aged; Cytokines; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Receptors, Cytokine; Regression Analysis

Asleep blood pressure (BP) has been shown to better reflect cardiovascular risk than awake BP in hypertensive patients. This study investigated the correlation of brain natriuretic peptide (BNP) to asleep BP during antihypertensive treatment.. In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which was an open-label multicenter trial to compare bedtime or awakening dosing of candesartan (+ diuretics as needed) among individuals with home SBP higher than 135  mmHg, we evaluated 254 hypertensive patients who underwent ambulatory BP monitoring, and measured their BNP at baseline and after 6th month of treatment.. At follow-up, the decrease in log-transformed BNP was significantly related to the decrease in asleep SBP (r = 0.27, P < 0.001); the relationship remained significant (β = 0.20, P = 0.002) even after adjusting for the decrease in the awake SBP (β = 0.001, P = 0.991). When we divided participants by their time of candesartan administration, the relationship between the decrease in log-transformed BNP and asleep SBP was still significant in both the awakening-dosing group (β = 0.21, P = 0.028) and the bedtime-dosing group (β = 0.21, P = 0.029). Furthermore, this relationship was strong in the participants who were receiving diuretics.. The decrease in BNP is associated with asleep BP reduction by candesartan (+ diuretics as needed) over and above the awake BP reduction, regardless of the time of administration.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Female; Humans; Hypertension; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Sleep; Tetrazoles; Time Factors

Overaggressive fluid resuscitation in elderly patients requiring pancreatectomy can delay recovery and increase morbidity. Despite advancements, no accurate and reproducible methods exist to evaluate effective intravascular volume status in the postoperative setting. We hypothesized that sequential measurement of currently available serum proteins will indicate fluid balance.. Clinicopathologic (n = 44) and echocardiogram (echo) data (n = 18) were collected on patients receiving pancreatectomy or diagnostic laparoscopy (n = 5). Measured fluid balance, serum BUN, creatinine (CR), and brain natriuretic peptide (BNP) levels were recorded on postoperative days (POD) 1 to 7 (only POD1 for diagnostic laparoscopy). ANOVA and bivariate random effect models examined the correlation between BNP and BUN/CR and fluid balance. Linear mixed-effect models examined the correlation between factors associated with vascular stiffness and BNP, BUN/CR, and fluid balance.. On POD1 after diagnostic laparoscopy, the fluid balance was positive by 3,265 mL and was accompanied by a >300-point increase in BNP (p = 0.0083). After pancreatectomy, a similar increase in BNP (250 pg/mL) and fluid balance (4,492 mL) on POD1 was observed. During the return to euvolemia, the change in serum BNP levels correlated with fluid balance changes during POD 1 to 3 (p = 0.039), and BUN/CR levels correlated with fluid balance during POD 4 to 7. Patients with risk factors associated with cardiovascular stiffness or echo evidence of poor compliance experienced higher BNP during the postoperative period.. Fluid loading at surgery is accompanied by an increase in serum BNP, and return to a balanced fluid state after pancreatectomy is paralleled by changes in BNP and BUN/CR levels.

Topics: Aged; Analysis of Variance; Cardiomegaly; Elasticity; Environmental Monitoring; Female; Heart Atria; Humans; Hypertension; Laparoscopy; Length of Stay; Male; Middle Aged; Models, Biological; Natriuretic Peptide, Brain; Pancreatectomy; Postoperative Care; Postoperative Complications; Retrospective Studies; Ultrasonography; Water-Electrolyte Balance

Topics: Humans; Hypertension; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain

Topics: Antihypertensive Agents; Blood Pressure; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Sleep

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women ≥65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 ± 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults.

Topics: Aged; Atrial Fibrillation; C-Reactive Protein; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Lipoproteins, HDL; Lipoproteins, LDL; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Sex Factors; Triglycerides; United States

Evidence has shown that endoplasmic reticulum stress (ERS) is associated with the pathogenesis of cardiac hypertrophy. The aim of this study was to investigate whether direct alleviation of ER stress by 4-phenylbutyric acid (PBA), a known chemical chaperone drug, could attenuate pressure-overload cardiac hypertrophy in mice. The effects of orally administered PBA (100mg/kg body weight daily for a week) were examined using mice undergoing transverse aortic constriction (TAC-mice), an animal model to produce pressure overload. TAC application for 1 week led to a 1.8-fold increase in the ratio of the heart weight over body weight (HW/BW) and up-regulation of the hypertrophy markers ANF and BNF accompanied by up-regulation of ERS markers (GRP78, p-PERK, and p-elF2α). The oral administration of PBA to the TAC-mice reduced hypertrophy (19%) and severely downregulated the fibrosis-related genes (transforming growth factor-β1, phospho-smad2, and pro-collagen isoforms). We conclude that ERS is induced as a consequence of remodeling during pathological hypertrophy and that PBA may help to relieve ERS and play a protective role against cardiac hypertrophy and possibly heart failure. We suggest PBA as a novel therapeutic agent for cardiac hypertrophy and fibrosis.

Topics: Administration, Oral; Animals; Aorta; Apoptosis; Atrial Natriuretic Factor; Biomarkers; Cardiomegaly; Disease Models, Animal; DNA-Binding Proteins; eIF-2 Kinase; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Hypertension; Mice; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phenylbutyrates; Pressure; Transcription Factors; Unfolded Protein Response

The renin-angiotensin-aldosterone system is involved in the arterial hypertension-associated cardiovascular remodeling. In this context, the development of cardiac fibrosis results from an imbalance between profibrotic and antifibrotic pathways, in which the role of aldosterone is yet not established. To determine the role of intracardiac aldosterone in the development of myocardial fibrosis during hypertension, we used a double transgenic model (AS-Ren) of cardiac hyperaldosteronism (AS) and systemic hypertension (Ren). The 9-month-old hypertensive mice had cardiac fibrosis, and hyperaldosteronism enhanced the fibrotic level. The mRNA levels of connective tissue growth factor and transforming growth factor-β1 were similarly increased in Ren and AS-Ren mice compared with wild-type and AS mice, respectively. Hyperaldosteronism combined with hypertension favored the macrophage infiltration (CD68(+) cells) in heart, and enhanced the mRNA level of monocyte chemoattractant protein 1, osteopontin, and galectin 3. Interestingly, in AS-Ren mice the hypertension-induced increase in bone morphogenetic protein 4 mRNA and protein levels was significantly inhibited, and B-type natriuretic peptide expression was blunted. The mineralocorticoid receptor antagonist eplerenone restored B-type natriuretic peptide and bone morphogenetic protein 4 levels and decreased CD68 and galectin 3 levels in AS-Ren mice. Finally, when hypertension was induced by angiotensin II infusion in wild-type and AS mice, the mRNA profiles did not differ from those observed in Ren and AS-Ren mice, respectively. The aldosterone-induced inhibition of B-type natriuretic peptide and bone morphogenetic protein 4 expression was confirmed in vitro in neonatal mouse cardiomyocytes. Altogether, we demonstrate that, at the cardiac level, hyperaldosteronism worsens hypertension-induced fibrosis through 2 mineralocorticoid receptor-dependent mechanisms, activation of inflammation/galectin 3-induced fibrosis and inhibition of antifibrotic factors (B-type natriuretic peptide and bone morphogenetic protein 4).

Topics: Aldosterone; Animals; Animals, Newborn; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Blood Pressure; Blotting, Western; Bone Morphogenetic Protein 4; Cells, Cultured; Cytochrome P-450 CYP11B2; Eplerenone; Female; Fibrosis; Galectin 3; Gene Expression; Hyperaldosteronism; Hypertension; Male; Mice; Mice, Transgenic; Mineralocorticoid Receptor Antagonists; Myocardium; Natriuretic Peptide, Brain; Organ Size; Renin; Reverse Transcriptase Polymerase Chain Reaction; Spironolactone

Cardiac remodeling is a deleterious consequence of arterial hypertension. This remodeling results in cardiac transcriptomic changes induced by mechanical and hormonal factors (angiotensin II and aldosterone are the most important). The major features of cardiac remodeling are the hypertrophy of cardiomyocytes, interstitial and perivascular fibrosis, and microvascular rarefaction. Inappropriate stimulation of the renin-angiotensin-aldosterone system (RAAS) participates to the development of heart failure. The respective roles of angiotensin II and aldosterone in cardiac remodeling are poorly understood. The development of fibrosis in the heart depends of a balance between profibrotic (TGFβ, CTGF, inflammation) and antifibrotic (BNP, ANP, BMP4 and BMP7) factors. The profibrotic and proinflammatory effects of angiotensin II and aldosterone are very well demonstrated; however, their actions on antifibrotic factors expression are unknown. In order to explore this, we used RenTgKC mice overexpressing renin into the liver, leading to an increased plasma angiotensin II and thus induction of severe hypertension, and AS mice overexpressing aldosterone synthase (AS) in cardiomyocytes which have a doubled intracardiac aldosterone concentration. Male AS mice have a dysfunction of the coronary arteries relaxation without structural and functional changes of the myocardium. Mice derived from a crossing between the RenTgKC and AS strains were used in this work. It is shown that angiotensin II induces the expression of BNP and BMPs which ultimately slows the progression of myocardial fibrosis, and that aldosterone inhibits the expression of these factors and thus worsens the fibrosis.

Topics: Aldosterone; Angiotensin II; Animals; Bone Morphogenetic Proteins; Cardiomegaly; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Heart Failure; Hypertension; Male; Mice; Mice, Transgenic; Myocytes, Cardiac; Natriuretic Peptide, Brain; Renin; Renin-Angiotensin System

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r=0.639; P<0.001), insoluble stiff collagen (r=0.474; P<0.005), CCL (r=0.625; P<0.001), and LOX (r=0.410; P<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r=0.612; P<0.005), LOX (r=0.538; P<0.01), left ventricular chamber stiffness constant (r=0.535; P<0.005), peak filling rate (r=-0.343; P<0.05), ejection fraction (r=-0.430; P<0.01), and amino-terminal propeptide of brain natriuretic peptide (r=0.421; P<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.

Topics: Biomarkers; Case-Control Studies; Collagen; Collagen Type I; Comorbidity; Echocardiography; Heart Failure; Humans; Hypertension; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Protein-Lysine 6-Oxidase; Pulmonary Wedge Pressure; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left

We studied relationship between structure-functional parameters of left and right cardiac chambers and N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 118 patients with arterial hypertension (AH) (35 men, 83 women) and 17 healthy volunteers. Methods comprised 24-hour arterial pressure monitoring (APM), two-dimensional echocardiography (echoCG), Doppler echoCG, and tissue echoCG of mitral and tricuspid atrioventricular annuli, treadmill test, 6-min walk test, and measurement of NT-proBNP level in blood plasma. In patients with AH blood plasma NT-proBNP level was significantly higher than in a group of healthy persons of similar age. Elevation of this biochemical marker was accompanied by significant change of characteristics of remodeling of left and right parts of the heart, abnormalities of left ventricular diastolic function according to transmitral blood flow, disturbances of left ventricular diastolic and systolic function according to tissue Doplerography data. Comparative analysis of structure-functional parameters of the heart and NT-proBNP level in patients with AH allowed to reveal more significant changes of parameters of diastolic and systolic remodeling, local and global diastolic and systolic left ventricular function in patients with NT-proBNP levels more than 306 mol/ml. Factors determining NT-proBNP level in patients with AH were age, free right ventricular wall thickness, and body mass index.

Topics: Adult; Biomarkers; Body Mass Index; Echocardiography, Doppler; Exercise Test; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Right Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Research Design; Statistics as Topic; Ventricular Dysfunction; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography.. The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E' (correlation coefficient (r) = -0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and -0.626 for E/E', p = 0.002, respectively) while positively correlated with E/A and E'/A' (r = 0.683 for E/A, p = 0.001, 0.671 for E'/A', p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found.. Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Topics: Adiponectin; Animals; Base Sequence; Biomarkers; Diastole; Disease Progression; Gene Expression; Heart Failure; Hypertension; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Fragments; Rats; Rats, Inbred SHR; RNA, Messenger; Systole; Ultrasonography

The aim of this study was to determine the prevalence of heart failure (HF) in adult residents of Turkey based on echocardiography and N-terminal B type natriuretic factor.. 4650 randomly selected residents aged ≥ 35 years were enrolled. Height, weight, waist and hip circumference, and blood pressure measurements were taken, and a 12-lead ECG was performed. Advanced age, hypertension (HT), diabetes mellitus (DM), obesity, and chronic renal failure (CRF) were assessed. History of any heart disease, any abnormal ECG, or an NT-proBNP ≥ 120 pg/mL was accepted as echocardiography indication. Patients with systolic and/or diastolic dysfunction, or NT-proBNP ≥ 2000 pg/mL were classified as having HF if their functional capacity was NYHA ≥ Class II, and were classified as having asymptomatic left ventricular dysfunction (ASVD) if their functional capacity was NYHA

Topics: Adult; Age Factors; Aged; Echocardiography; Electrocardiography; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Risk Factors; Sex Factors; Turkey; Ventricular Dysfunction, Left

There are controversies concerning the capacity of Rosuvastatin to attenuate heart failure in end-stage hypertension. The aim of the study was to show whether the Rosuvastatin might be effective or not for the heart failure treatment. Twenty-one spontaneously hypertensive rats (SHRs) aged 52 weeks with heart failure were randomly divided into three groups: two receiving Rosuvastatin at 20 and 40 mg/kg/day, respectively, and the third, placebo for comparison with seven Wistar-Kyoto rats (WKYs) as controls. After an 8-week treatment, the systolic blood pressure (SBP) and echocardiographic features were evaluated; mRNA level of B-type natriuretic peptide (BNP) and plasma NT-proBNP concentration were measured; the heart tissues were observed under electron microscope (EM); myocardial sarcoplasmic reticulum Ca(2+) pump (SERCA-2) activity and mitochondria cytochrome C oxidase (CCO) activity were measured; the expressions of SERCA-2a, phospholamban (PLB), ryanodine receptor2 (RyR2), sodium-calcium exchanger 1 (NCX1), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase inhibitor-1 (PPI-1) were detected by Western blot and RT-qPCR; and the total and phosphorylation of protein kinase Cα/β (PKCα/β) were measured. Aged SHRs with heart failure was characterized by significantly decreased left ventricular ejection fraction and left ventricular fraction shortening, enhanced left ventricular end-diastolic diameter and LV Volume, accompanied by increased plasma NT-proBNP and elevated BNP gene expression. Damaged myofibrils, vacuolated mitochondria and swollen sarcoplasmic reticulum were observed by EM. Myocardium mitochondria CCO and SERCA-2 activity decreased. The expressions of PLB and NCX1 increased significantly with up-regulation of PPI-1 and down-regulation of CaMKII, whereas that of RyR2 decreased. Rosuvastatin was found to ameliorate the heart failure in aged SHRs and to improve changes in SERCA-2a, PLB, RyR2, NCX1, CaMKII and PPI-1; PKCα/β2 signal pathway to be suppressed; the protective effect of Rosuvastatin to be dose dependent. In conclusion, the heart failure of aged SHRs that was developed during the end stage of hypertension could be ameliorated by Rosuvastatin.

Topics: Aging; Animals; Blood Pressure; Calcium-Binding Proteins; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Down-Regulation; Electron Transport Complex IV; Fluorobenzenes; Heart Failure; Hypertension; Male; Mitochondria; Myofibrils; Natriuretic Peptide, Brain; Peptide Fragments; Phosphorylation; Protein Kinase C beta; Protein Kinase C-alpha; Proteins; Pyrimidines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Rosuvastatin Calcium; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Sodium-Calcium Exchanger; Stroke Volume; Sulfonamides; Up-Regulation; Ventricular Function, Left

The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodeling. Corresponding changes in three-dimensional organization of cardiac extracellular matrix have not been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and morphological data, brain natriuretic peptide levels, and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure, and decompensated HF. Passive left ventricular (LV) pressure-volume relationships were determined in vitro. Transmural specimens from the anterior LV free wall were imaged using extended-volume confocal microscopy, and three-dimensional myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 mo and increased progressively thereafter. However, it was less than in controls for filling pressures <10 mmHg and not significantly different at ≥10 mmHg. Myocyte cross section was enlarged, with increased variability from 12 mo, while collagen fraction increased progressively. Perimysial collagen fraction remained unchanged with age, although endomysial collagen increased from 12 mo. Perimysial collagen between adjacent muscle layers fused at 12 mo and continued to thicken subsequently, while muscle layers became more dispersed and disordered. We conclude that LV dilatation, which accompanies decompensated HF in this model of HHD, is not due to LV "softening." While perimysial (and endomysial) collagen networks are substantially remodeled, they are not dissolved, as has been proposed. We argue that progressive disruption of the laminar organization of LV myocardium may contribute to impaired systolic function in HHD.

Topics: Animals; Collagen; Disease Models, Animal; Disease Progression; Echocardiography; Heart Failure; Heart Ventricles; Hypertension; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

This study sought to investigate plasma levels of circulating cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP), in the general community, focusing on their relative differences in worsening human hypertension.. Although ANP and BNP are well-characterized regulators of blood pressure in humans, little is known at the population level about their relationship with hypertension. The authors hypothesized that hypertension is associated with a lack of activation of these hormones or their molecular precursors.. The study cohort (N = 2,082, age >45 years) was derived from a random sample from Rochester, Minnesota, and each subject had a medical history, clinical examination, and assessment of different plasma forms of ANP and BNP. Patients were stratified by blood pressure. Multivariable linear regression was used to assess differences in natriuretic peptide levels in worsening hypertension.. Compared to normotensive, BNP(1-32) and N-terminal proBNP(1-76) (NT-proBNP(1-76)) were significantly decreased in pre-hypertension (p < 0.05), with BNP(1-32) significantly decreased in stage 1 as well (p < 0.05). Although proBNP(1-108) remained unchanged, the processed form was significantly increased only in stage 2 hypertension (p < 0.05). ANP(1-28) remained unchanged, while NT-ANP(1-98) was reduced in pre-hypertension (p < 0.05).. The authors demonstrated the existence of an impaired production and/or release of proBNP(1-108) along with a concomitant reduction of BNP(1-32) and NT-proBNP(1-76) in the early stages of hypertension, with a significant elevation only in stage 2 hypertension. Importantly, they simultaneously demonstrated a lack of compensatory ANP elevation in advanced hypertension.

Topics: Aged; Atrial Natriuretic Factor; Female; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain

The aim of this study was to compare the effectiveness of transient prehypertensive treatment with losartan compared with amlodipine in spontaneously hypertensive rats (SHRs) on long-term blood pressure (BP), cardiac and renal protection. SHRs were prehypertensively treated with losartan, amlodipine or saline. Rats were followed up until 46 weeks of age. The left ventricular (LV) geometry and function were assessed by echocardiography. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassay. Ang II type 1 (AT1R) and type 2 (AT2R) receptor protein expression was determined by western blotting. The systolic blood pressure (SBP) in losartan-treated SHRs (SHR-Los) was persistently reduced until 46 weeks of age, but returned to untreated SHR levels in amlodipine-treated SHRs (SHR-Aml) from 30 weeks onwards. Compared to untreated SHRs, the albuminuria excretion in SHR-Los at week 46 was markedly decreased, the plasma, myocardium and renal tissue Ang II and Aldo levels in SHR-Los at week 46 were markedly decreased; AT1R and TGF-β1 protein expression was downregulated and AT2R protein was upregulated. Compared to untreated SHRs, the left ventricular mass index (LVMI) and collagen volume fraction (CVF) in SHR-Los were markedly decreased until week 46, and the left ventricular ejection fraction (LVEF) and cardiac brain natriuretic peptide mRNA expression were improved, whereas similar LVMI and elevated CVF were observed in SHR-Aml, and the LVEF decreased significantly below that of untreated SHRs at week 46, with cardiac BNP mRNA expression increasing slightly. Prehypertensive treatment with losartan was more effective than amlodipine on delaying long-term BP increase and ameliorating cardiac, renal structure and function, which may be related to the permanent attenuation of the circulating and local renin-angiotensin systems.

Topics: Aldosterone; Amlodipine; Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Cardiotonic Agents; Collagen; Gene Expression Regulation; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Kidney; Losartan; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Stroke Volume; Transforming Growth Factor beta1; Ultrasonography

Cardiovascular hypertrophy is a common feature of hypertension and an important risk factor for heart damage. The regression of cardiovascular hypertrophy is currently considered an important therapeutic target in reducing the omplications of hypertension. The aim of this study was to investigate the inhibition of cardiac hypertrophy by probiotic-fermented purple sweet potato yogurt (PSPY) with high γ-aminobutyric acid (GABA) content in spontaneously hypertensive rat (SHR) hearts. Six-week-old male SHRs were separated randomly and equally into 4 experimental groups: sterile water, captopril and 2 PSPY groups with different doses (10 and 100%) for 8 weeks. The changes in myocardial architecture and key molecules of the hypertrophy-related pathway in the excised left ventricle from these rats were determined by histopathological analysis, hematoxylin and eosin staining and western blot analysis. Abnormal myocardial architecture and enlarged interstitial spaces observed in the SHRs were significantly decreased in the captopril and PSPY groups compared with the sterile water group. Moreover, the increases in atrial natriuretic peptide, B-type natriuretic peptide, phosphorilated protein kinase Cα and calmodulin-dependent protein kinase II levels in the left ventricle were accompanied by hypertension and increases in phosphorylated extracellular signal-regulated kinase 5 activities with enhanced cardiac hypertrophy. However, the protein levels of the hypertrophic-related pathways were completely reversed by the administration of PSPY. PSPY may repress the activation of ANP and BNP which subsequently inhibit the dephosphorylation of the nuclear factor of activated T-cells, cytoplasmic 3 and ultimately prevent the progression of cardiac hypertrophy.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Calcineurin; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Captopril; gamma-Aminobutyric Acid; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Insulin-Like Growth Factor II; Interleukin-6; Ipomoea batatas; Male; Mitogen-Activated Protein Kinase 7; Natriuretic Peptide, Brain; NFATC Transcription Factors; Organ Size; Protein Kinase C-alpha; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Yogurt

Insulin resistance (IR) is part of the metabolic syndrome (Mets) that develops after lifestyle changes and obesity. Although the association between Mets and myocardial injury is well known, the effect of IR on myocardial damage remains unclear.. We studied 2200 normal subjects who participated in a community-based health check in the town of Takahata in northern Japan. The presence of IR was assessed by homeostasis model assessment ratio, and the serum level of heart-type fatty acid binding protein (H-FABP) was measured as a maker of silent and ongoing myocardial damage. H-FABP levels were significantly higher in subjects with IR and Mets than in those without metabolic disorder regardless of gender. Multivariate logistic analysis showed that the presence of IR was independently associated with latent myocardial damage (odds ratio: 1.574, 95% confidence interval 1.1-2.3) similar to the presence of Mets.. In a screening of healthy subjects, IR and Mets were similarly related to higher H-FABP levels, suggesting that there may be an asymptomatic population in the early stages of metabolic disorder that is exposed to myocardial damage and might be susceptible to silent heart failure.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Cross-Sectional Studies; Early Diagnosis; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Humans; Hypertension; Incidence; Insulin Resistance; Japan; Male; Mass Screening; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Sex Characteristics

Despite advances in medicine, chronic systolic heart failure (CHF) due to hypertension still constitutes a serious clinical challenge.. The aim of the study was to determine risk mortality factors in a 3-year follow-up of patients with CHF due to hypertension.. The study involved 140 consecutive stable inpatients with CHF (left ventricular end diastolic diameter >57 mm; left ventricular ejection fraction [LVEF] <40%), without epicardial artery stenosis (>30% vessel lumen), significant heart defect, diabetes, neoplastic, disease, or chronic kidney disease, with a minimum 5-year history of hypertension, and administration of angiotensin-converting enzyme inhibitors (or angiotensin II receptor antagonists), β-adrenolytics, spironolactone and furosemide for 3 or more months. The follow-up began on admission to the hospital after laboratory tests, resting electrocardiogram and echocardiogram, six-minute walk test, coronarography, and endomyocardial biopsy. Late follow-up data was obtained from the follow-up visits or by telephone.. The analysis involved 130 of 140 patients aged 47.8 ±7.9 years. The 3-year mortality rate was 18.5%. Independent risk factors for death were LVEF (hazard ratio [HR], 0.881; 95% confidence interval [CI], 0.797-0.975, P <0.05), serum glucose (HR, 1.266; 95% CI, 1.085-1.627; P <0.05), N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.369; 95% CI, 1.166-1.671; P <0.001), and bilirubin levels (HR, 1.057; 95% CI, 1.021-1.094; P <0.01).. Beside LVEF and serum NT-proBNP, other independent risk factors for death in patients with CHF due to hypertension are glucose and bilirubin levels.

Topics: Adult; Aged; Biomarkers; Causality; Chronic Disease; Comorbidity; Confidence Intervals; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Ventricles; Hospitalization; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prognosis; Severity of Illness Index; Survival Analysis; Troponin T

In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

Topics: Aged; Biomarkers; Coronary Sinus; Extracellular Matrix; Female; Humans; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Male; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Remodeling

We assessed gender differences in variables related to B-natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), peak oxygen consumption (peak-VO2), and LV mass (LVM), among patients recently hospitalized for suspected heart failure (HF).. Of 930 consecutive patients, 409 accepted follow-up after discharge, 221 of these had definite HF (90 women, mean age 74.5 [9.8]years). In 141 HF patients (61 women) with BNP data, women had lower BNP than men (43.9 [38.1] versus 76.3 [88.9]pmol/L, P=0.0193). LVEF (all HF patients) was higher in women (49.8 [13.4] versus 42.4 [13.9]%, P=0.0004). Peak-VO2 (147 HF patients, 48 women) was lower in women (13.9 [4.3] versus 16.3 [4.2]mL/kg/min, P=0.0093). LVM index (200 HF patients, 78 women) was lower in women (130.4 [46.5] versus 171.7 [57.6]g/m(2), P<0.0001). Among HF patients, variables independently related to BNP were body mass index (BMI) and peak-VO2 exclusively among men, mitral regurgitation, respiratory disease and angiotensin receptor blocker treatment only among women. Variables independently related to LVEF were resting heart rate, acetylic salicylic acid use and BNP exclusively among men. No variable was exclusive for women. Variables independently related to peak-VO2 were right ventricular size, BNP, resting and peak heart rate solely among men, BMI and stable angina pectoris exclusively among women. Variables independently related to LVM were left atrial diameter only among men, BMI exclusively among women.. Among elderly HF patients, there were some important gender differences in BNP, LVEF, peak-VO2 and LVM, and in variables independently related to these factors.

Topics: Aged; Aged, 80 and over; Comorbidity; Female; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Oxygen Consumption; Risk Factors; Sex Characteristics; Sex Distribution; Stroke Volume; Ventricular Function, Left

The mechanisms underlying the increased cardiovascular risk after menopause are poorly understood. Estrogens modulate the cardiac renin-angiotensin system (RAS) and influence cardiac adaptation to afterload. To investigate whether the loss of the natural inhibition of the RAS by estrogen may be linked to an increase of cardiac apoptosis, we studied 17β-estradiol (E2) and/or angiotensin-converting enzyme (ACE) inhibitor treatment effects on cardiomyocyte survival in ovariectomized spontaneously hypertensive rats (SHRs).. Five groups of female SHRs were evaluated for 8 weeks. One group served as nonovariectomized control; the other four groups underwent bilateral ovariectomy and were randomized to receive 60-day-release pellets containing placebo or 0.5 mg of E2, the ACE inhibitor ramipril at the dosage of 2.5 mg/kg per day, or the combination of the two treatments.. Ovariectomy increased cardiomyocyte apoptosis and induced proapoptotic changes of Bcl-2 and Bax genes and proteins. These modifications were associated with an upregulation of ACE and angiotensin II type 1 (AT1) receptor genes. Ramipril was as effective as E2 in preventing cardiac apoptosis and in restoring cardiac brain natriuretic peptide in association with reduced cardiac ACE and AT1 receptor gene expression. In contrast to the ramipril treatment, the favorable effect of E2 on cardiac apoptosis occurred independently from changes in SBP. No synergistic effect was observed when the two treatments were combined.. These data show that ovariectomy stimulates myocardium apoptosis by a mechanism involving Bax and Bcl-2 genes. The antiapoptotic effect of E2 and ACE inhibitor treatment was linked to a downregulation of cardiac RAS.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Base Sequence; bcl-2-Associated X Protein; DNA Primers; Estradiol; Female; Gene Expression; Genes, bcl-2; Heart; Hypertension; Myocardium; Natriuretic Peptide, Brain; Ovariectomy; Peptidyl-Dipeptidase A; Ramipril; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Renin-Angiotensin System

The efficacy of out-patient cardiac rehabilitation (OPCR) in patients with a low prognostic risk after acute myocardial infarction (AMI) is unclear in the recent primary intervention era.. A total of 637 AMI patients who participated in in-hospital cardiac rehabilitation were divided into 2 groups; low prognostic risk group (n=219; age <65 years, successful reperfusion, Killip class I, peak serum creatine kinase <6,000U/L, and left ventricular ejection fraction ≥40%) and non-low prognostic risk group (n=418). The prevalence of coronary risk factors (CRF) was compared between the 2 groups. Then, in the low-risk group, the efficacy of OPCR was compared between active OPCR participants (n=52; ≥20 sessions/3 months) and non-active participants (n=60; <6 sessions/3 months). Compared with the non-low prognostic risk group, the low prognostic risk group had a significantly higher prevalence of current smokers (72% vs. 49%, P<0.05) and patients with multiple CRF (3 or more; 49% vs. 39%, P<0.05). Among the low- risk group, active OPCR participants showed a significantly greater improvement in exercise capacity (peak VO(2), P<0.05) and maintained a better CRF profile (total cholesterol, triglyceride and blood pressure, all P<0.05) than inactive participants at 3 months.. Low prognostic risk AMI patients have a higher prevalence of multiple CRF than non-low risk patients. Even in this low risk group, active participation in OPCR is associated with improved exercise capacity and better CRF profile.

Topics: Ambulatory Care; Biomarkers; Cardiovascular Agents; Comorbidity; Creatine Kinase; Dyslipidemias; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Prognosis; Retrospective Studies; Risk; Smoking; Stroke Volume; Treatment Outcome

To evaluate the biological variation and prognostic value of brain natriuretic peptide (BNP) for stable outpatients with nonischemic chronic heart failure (NICHF).. Biological variation in BNP was evaluated using an automated assay system in 140 outpatients with NICHF. The stable clinical condition during the 2-month study period was defined as unchanged NYHA and unchanged left ventricular ejection fraction; therefore, 7 patients were excluded during the 2 months. Thereafter, 133 patients were prospectively followed and the relationship between cardiac events and the plasma BNP concentrations (at baseline and after 2 months) were evaluated as well as the changes in BNP. The biological variation in BNP (2-month interval) was calculated as 22.3%. During a mean follow-up period of 42 months, 26 patients had cardiac events. According to stepwise multivariate analyses, plasma BNP after 2 months (P=0.0002) and % change in BNP (P=0.0067) were significant independent predictors of cardiac events.. These findings indicated that a combination of the absolute value of BNP after 2 months and % increase in BNP (2-month interval) is useful for predicting cardiac events in stable outpatients with NICHF.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiomyopathy, Dilated; Creatinine; Female; Follow-Up Studies; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Outpatients; Prognosis; Prospective Studies; ROC Curve; Stroke Volume

Early detection of left ventricular hypertrophy (LVH) is beneficial, since treatment-induced regression of LVH has been unequivocally associated with a better prognosis. Our aim was to study the relation of cardiac remodelling and natriuretic peptides (NPs) in stage 1 hypertension. We studied 175 (46±7 years, 87 women and 88 men) apparently healthy middle-aged that had never been treated for hypertension. Left ventricular and atrial parameters were determined by magnetic resonance imaging. Systolic blood pressure (BP) correlated with left ventricular mass index (LVMI) (r=0.23, P<0.01) and ventricular septum thickness index (IVSI) (r=0.29, P<0.001). N-terminal pro-B-type NP (NT-proBNP) or N-terminal pro-atrial NP (NT-proANP) did not correlate with BP, LVMI or IVSI. NT-proANP correlated with left atrial area index (LAAI) (r=0.38, P<0.001), and subjects with LVH had higher LAAI than subjects with normal left ventricular geometry and no LVH (11.2±0.3 vs 10.0±0.2 cm(2) m(-2), P<0.001). In conclusion, measurement of NT-proBNP or NT-proANP does not appear to discriminate LVH in middle-aged, never treated and apparently healthy hypertensives. NT-proANP, but not NT-proBNP, reflects early cardiac remodelling in hypertensive heart disease.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Incidence; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Ventricular Remodeling

Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.. Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.. LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.

Topics: Actins; Aged; Asymptomatic Diseases; Biomarkers; Chi-Square Distribution; Coronary Sinus; Echocardiography, Doppler; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Heart Failure; Humans; Hypertension; Immunohistochemistry; Interleukin-6; Ireland; Logistic Models; Male; Mass Spectrometry; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Protein Serine-Threonine Kinases; Proteomics; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

Dual renin-angiotensin system (RAS) blockade has no more efficiency to decrease cardiovascular mortality than mono-blockade. Our goal was to explore differences between other cardiovascular markers in patients with RAS blockade.. We analyzed two groups of patients treated with a long-term ACE inhibitor (MONO-group, n = 20) and an ACE inhibitor and angiotensin II receptor blocker (DUAL-group, n = 15). Ambulatory blood pressure monitoring, echocardiography, arterial stiffness and levels of catecholamine, endogenous ouabain (EO), pro-brain natriuretic peptide and more types of urinary albumin measurements were performed.. In the DUAL-group, we found significantly better cardiac parameters, but the levels of EO and urinary albumins were similar in both groups. The level of EO correlates with nighttime mean arterial blood pressure (R = 0.556, p = 0.032) and arterial β-stiffness (R = 0.512, p = 0.042). Urinary immuno-unreactive albumin showed a relationship with diastolic dysfunction of the heart (R = -0.508, p = 0.045) diurnal index of diastolic blood pressure (R = -0.569, p = 0.021) in the MONO-group.. Cardiac parameters were more prosperous in the DUAL-group, but the levels of EO did not differ between groups. The level of EO correlated with blood pressure and arterial stiffness markers in the MONO-group only. The urinary immuno-unreactive albumin may be a new marker of cardiovascular conditions.

Topics: Aged; Albumins; Arteries; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Physiological Phenomena; Catecholamines; Cross-Sectional Studies; Diabetic Nephropathies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nephrosclerosis; Ouabain; Peptide Fragments; Renal Insufficiency; Renin-Angiotensin System; Retrospective Studies

The cardiac left ventricle responds to pressure overloads with mechanisms culminating in irreversible structural/functional cardiac alterations (left ventricular hypertrophy and/or diastolic dysfunction), inducing myocardial cells to secrete natriuretic peptides (NT-proBNP) antagonists of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the diagnostic accuracy of serum NT-proBNP levels in order to detect structural/functional cardiac diseases assessed by echocardiography.. A total of 126 consecutive newly diagnosed, never before treated, hypertensive patients (30-67 years) were enrolled, and clinical, echocardiography parameters and biochemical data were collected. Our reference was the presence of structural/functional cardiac disease (CSFD) and our index text was the serum NT-proBNP levels.. NT-proBNP levels in CSFD patients were ~2 times higher than in non-CSFD subjects (median 61 vs 29 ng/L, n=50 and 76, respectively); in addition, 60% of CSFD subjects (only 14% of which with pathological levels, >125 ng/L), and 30% without CSFD showed NT-proBNP concentrations higher than 50 ng/L. However, ROC curves demonstrated a low specificity (38%) (calculated at 90% sensitivity at a cut-off of 22.5 ng/L).. NT-proBNP levels, as a screening tool for cardiac structural/functional disease, appear to be limited, because of the low specificity. However, the strong association between its concentration and the establishment of irreversible cardiac hypertrophy prompts successive studies aimed to ascertain the use of its serum levels as an early alert indicator of disease severity.

Topics: Adult; Aged; Biomarkers; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve

Topics: Humans; Hypertension; Natriuretic Peptide, Brain; Risk

Natriuretic peptides are controregulatory hormones associated with cardiac remodeling, namely, left ventricular hypertrophy and systolic/diastolic dysfunction. We intended to address the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in hypertension. We prospectively studied the relationship between plasma NT-proBNP and all-cause mortality in 684 hypertensive patients with no history or symptoms of heart failure referred for hypertension workup in our institution from 1998 to 2008. After a mean duration of 5.7 years, we observed 40 deaths (1.04 deaths per 100 patients per year). After adjustment for traditional cardiovascular risk factors, including ambulatory blood pressure and serum creatinine, the risk for all-cause mortality more than doubled with each increment of 1 log NT-proBNP (hazard ratio: 2.33 [95% CI: 1.36 to 3.96]). The risk of death of patients with plasma NT-proBNP≥133 pg/mL (third tertile of the distribution) was 3.3 times that of patients with values<50.8 pg/mL (first tertile; hazard ratio: 3.30 [95% CI: 0.90 to 12.29]). This predictive value was independent of, and superior to, that of 2 ECG indexes of left ventricular hypertrophy, the Sokolov-Lyon index and the amplitude of the R wave in lead aVL. In addition, it persisted in patients without ECG left ventricular hypertrophy, which allowed refining risk stratification in this relatively low-risk patient category. In this large sample of hypertensive patients, plasma NT-proBNP appeared as a strong prognostic marker. This performance, together with the ease of measurement, low cost, and widespread availability of NT-proBNP test kits, should prompt a wide use of this marker for risk stratification in hypertension.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure Monitoring, Ambulatory; Echocardiography; Female; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Risk Factors; Survival Rate

We examined which echocardiographic parameter correlated best with plasma brain natriuteric peptide (BNP) levels in treated hypertensive patients. Enrolled in the study were 122 treated hypertensive patients (70 ± 9 y). The left ventricular mass index and left atrial dimension (LAD) were measured using echocardiography as indexes of left ventricular hypertrophy and left atrial enlargement, respectively. Among all the echocardiographic parameters, LAD correlated best with BNP (r = 0.343, p < 0.001). Stepwise regression analysis showed that LAD (β coefficient = 0.513, p < 0.001) was independently associated with BNP. Left atrial enlargement, rather than left ventricular hypertrophy, may be clinically useful for predicting elevated BNP levels in treated hypertensive patients.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Cross-Sectional Studies; Female; Heart Atria; Humans; Hypertension; Hypertrophy; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Ultrasonography

B-type natriuretic peptide (BNP) is an endogenous peptide produced under physiological and pathological conditions mainly by ventricular myocytes. It has natriuretic, diuretic, blood pressure-lowering, and antifibrotic actions that could mediate cardiorenal protection in cardiovascular diseases. In the present study, we used BNP gene transfer to examine functional and structural effects of BNP on left ventricular (LV) remodeling.. Human BNP was overexpressed by using adenovirus-mediated gene delivery in normal rat hearts and in hearts during the remodeling process after infarction and in an experimental model of angiotensin II-mediated hypertension. In healthy hearts, BNP gene delivery into the anterior wall of the LV decreased myocardial fibrosis (P<0.01, n=7 to 8) and increased capillary density (P<0.05, n=7 to 8) associated with a 7.3-fold increase in LV BNP peptide levels. Overexpression of BNP improved LV fractional shortening by 22% (P<0.05, n=6 to 7) and ejection fraction by 19% (P<0.05, n=6 to 7) after infarction. The favorable effect of BNP gene delivery on cardiac function after infarction was associated with normalization of cardiac sarcoplasmic reticulum Ca(2+)-ATPase expression and phospholamban Thr17-phosphorylation. BNP gene delivery also improved fractional shortening and ejection fraction in angiotensin II-mediated hypertension as well as decreased myocardial fibrosis and LV collagen III mRNA levels but had no effect on angiogenesis or Ca(2+)-ATPase expression and phospholamban phosphorylation.. Local intramyocardial BNP gene delivery improves cardiac function and attenuates adverse postinfarction and angiotensin II-induced remodeling. These results also indicate that myocardial BNP has pleiotropic, context-dependent, favorable actions on cardiac function and suggest that BNP acts locally as a key mechanical load-activated regulator of angiogenesis and fibrosis.

Topics: Adenoviridae; Angiotensin II; Animals; Collagen Type III; Disease Models, Animal; Fibrosis; Gene Transfer Techniques; Genetic Therapy; Humans; Hypertension; Ligation; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Organothiophosphorus Compounds; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Ventricular Dysfunction, Left; Ventricular Remodeling

To evaluate transient deceleration wave intensity (W2) of carotid artery on left ventricular diastolic function.. 40 patients with hypertension and 43 healthy volunteers were enrolled and W2 of carotid artery of the both sides were measured. The parameters of left ventricular diastolic function by traditional and tissue Doppler imaging and NT-proBNP (N-terminal probrain natriuretic peptide) were measured.. (1) W2 is not different between two sides of carotid artery. W2 in hypertension was lower than the control, especially in left side(1126 +/- 996 mmHg x m/s3 vs 1690 +/- 1126 mmHg x m/s3, P < 0.01). (2) The correlation of W2 and else parameters were analyzed. There were notably decreasing in left ventricular diastolic function of the hypertensive group than the control, for example, the ratio of peak velocity of early filling of mitral flow to peak early diastolic motion velocity of mitral annulus (E/Em, 9.37 +/- 3.32 vs 7.39 +/- 1.83, P < 0.01) and NT-proBNP (94.6 +/- 48.5 vs 45.2 +/- 13.8, P < 0.01). (3) The correlation analysis showed negative relation between W2 and E/Em (r = - 0.46, P < 0.05) and negative relation between W2 and NT-proBNP (r = -0.21, P < 0.05).. New carotid W2 by non-invasive technology for hemodynamics is a deserving parameter in early evaluating left ventricular diastolic function.

Topics: Adult; Carotid Artery, Common; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Glycopeptides; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume

Electrocardiography (ECG) is the most widely used method for diagnosing left ventricular hypertrophy (LVH) in hypertensive patients. We assessed the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) determination compared with ECG for detecting LVH in 336 consecutive hypertensive patients with preserved systolic function. We found a significant correlation between NT-proBNP levels and left ventricular mass adjusted for body surface area (r=.41; P<.001). The area under the receiver operating characteristic curve was 0.75 (95% CI, 0.7-0.8). A cut-off of 74.2 pg/mL had a greater sensitivity than ECG (76.6% vs 25.5%; P<.001) and a higher negative predictive value (87.8% vs 76.6%; P<.001) in the identification of LVH. NT-proBNP determination may be a useful tool for LVH screening in hypertensive patients.

Topics: Aged; Biomarkers; Blood Pressure; Body Mass Index; Electrocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors; ROC Curve

Long-term right ventricular apical pacing can cause ventricular dyssynchrony and, secondarily, neurohumoral alterations and increase in cardiac morbimortality.. To analyze ventricular dyssynchrony and its effects on BNP levels in patients with pacemakers and long-term right ventricular (RV) apex pacing.. Cross-sectional study of 85 patients with single or dual chamber pacemaker, NYHA functional class I or II and left ventricular ejection fraction (LVEF) ≥ 35%. The dyssynchrony assessment was carried out using several echocardiographic techniques, including Tissue Synchronization Imaging (TSI), with the analysis of the 12 segments. BNP was measured at the same time when the echocardiogram was performed, but the examiner was blinded to the results.. Forty-six women and 39 men, aged 58 ± 12 years, with Chagas' disease (56%) and controlled hypertensive individuals (62%), were included in the study. LVEF was 52 ± 8% and the mean QRS duration was 139 ms (120-180 ms). BNP levels were altered in 36.5% of the sample (cutoff = 60 pg/ml). At the multivariate linear regression analysis, BNP was correlated with age (p = 0.024), LVEF (p < 0.0001) and left ventricular (LV) pre-ejection time (p = 0.009), which is an intraventricular dyssynchrony index.. In clinically stable patients receiving conventional cardiac pacing, the intraventricular dyssynchrony was an independent predictor of BNP level increase after adjusted for age and LVEF.

Topics: Adult; Aged; Cardiac Pacing, Artificial; Chagas Disease; Epidemiologic Methods; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Right; Young Adult

BACKGROUND. Phaeochromocytomas and paragangliomas are rare, mostly benign catecholamine-producing tumours of chromaffin cells of the adrenal medulla or of extra-adrenal paraganglia. Phaeochromocytoma may occur at any age, the greatest frequency being in the fourth and fifth decades. Only on extremely rare occasions does the tumour develop in the very old patients. METHODS. We are describing an 86-year-old patient with phaeochromocytoma, presenting with reversible myocardial dysfunction. RESULTS. This very old patient with phaeochromocytoma had hypertension characterized by labile blood pressure values and increased daytime blood pressure variability. This patient exhibited reversible myocardial dysfunction suggestive for "catecholaminergic cardiomyopathy", as the complication of phaeochromocytoma. After surgical removal of the tumour, recovery of left ventricular function was documented by echocardiography showing normalization of systolic function and improvement of diastolic function. CONCLUSION. Phaeochromocytomas are rare forms of secondary hypertension, but should be considered in the differential diagnosis, regardless of age, even in very old patients.

Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Aged, 80 and over; Blood Pressure; Catecholamines; Diastole; Echocardiography; Follow-Up Studies; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pheochromocytoma; Poland; Systole; Tomography, X-Ray Computed; Ventricular Dysfunction, Left

Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.

Topics: Analysis of Variance; Animals; Aorta; Atrial Natriuretic Factor; Coronary Vessels; Disease Models, Animal; Disease Progression; Fibrosis; Gene Expression Regulation; Heart Failure; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Ligation; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stroke Volume; Time Factors; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Obesity is a risk factor for heart failure (HF). Paradoxically, it has been described that body mass index (BMI) is inversely associated with mortality. The aim of this study was to analyse the relationship between BMI and mortality in a cohort of patients with HF.. All patients included in the RICA Registry between March 2008 and September 2009 were analysed. RICA is a multicenter, prospective cohort study that includes patients admitted for decompensated HF in Spanish Internal Medicine Services. Patients were divided according to the WHO body weight categories.. 712 patients were included; 54% were women and mean age was 77.3 years. Hypertensive cardiopathy was the most common etiology of HF with some differences according to BMI categories, being valvular disease more frequent among obese and overweight patients and ischemic HF among normal weight patients. Mean left ventricle ejection fraction was 50.2% and it was higher among higher BMI categories. Natriuretic peptide levels were significantly lower among higher BMI categories (P<.05). Overall mortality after one-year of follow-up was 13.9% and it was significantly lower among higher BMI categories: normal BMI 20.4%, overweight 14.7% and obesity 8.5% (P<.01). In the multivariate analysis, overweight was significantly and independently associated with an increased mortality risk in comparison with obesity: RR 3.05 (IC95% 1.24-7.54).. An increase in BMI was associated with lower levels of natriuretic peptides and lower mortality.

Topics: Aged; Body Mass Index; Comorbidity; Diabetes Mellitus; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Kaplan-Meier Estimate; Male; Middle Aged; Models, Cardiovascular; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Prospective Studies; Registries; Risk; Spain

Topics: Animals; Atrial Natriuretic Factor; Endocrine System; Heart; Humans; Hypertension; Natriuretic Peptide, Brain

Lower plasma B-type natriuretic peptide (BNP) concentrations in obese individuals ("natriuretic handicap") may play a role in the pathogenesis of obesity-related hypertension. Whether this phenomenon may contribute to hypertension in blacks is unknown. We tested the hypothesis that body mass index is inversely related to BNP concentrations in blacks.. We examined the relation of plasma BNP to body mass index in 3742 Jackson Heart Study participants (mean age, 55 ± 13; 62% women) without heart failure using multivariable linear and logistic regression, adjusting for clinical and echocardiographic covariates. The multivariable-adjusted mean BNP was higher for lean participants compared with obese participants in both normotensive (P<0.0001) and hypertensive (P<0.0012) groups. In sex-specific analyses, the adjusted mean BNP was higher in lean hypertensive individuals compared with obese hypertensive individuals for both men (20.5 versus 10.9 pg/mL, respectively; P=0.0009) and women (20.0 versus 13.8 pg/mL; P=0.011). The differences between lean and obese participants were more pronounced in normotensive participants (men, 9.0 versus 4.4 pg/mL; P<0.0001; women, 12.8 versus 8.4 pg/mL; P=0.0005). For both hypertensive and normotensive individuals in the pooled sample, multivariable-adjusted BNP was significantly related to both continuous body mass index (P<0.05 and P<0.0001, respectively) and categorical body mass index (P for trend <0.006 and <0.0001, respectively).. Our cross-sectional study of a large community-based sample of blacks demonstrates that higher body mass index is associated with lower circulating BNP concentrations, thereby extending the concept of a natriuretic handicap in obese individuals observed in non-Hispanic whites to this high-risk population.

Topics: Adult; Aged; Black People; Body Mass Index; Cross-Sectional Studies; Female; Heart; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity

PURPOSE of this investigation was to study correlation between brain natriuretic peptide (BNP), extent of cardiac abnormalities, and six minute walk test (6-MWT) in order to asses diagnostic value of BNP in patients with trial fibrillation (F), heart failure (HF) and preserved systolic function.. Sixty five patients with history of hypertension, permanent F, and shortness of breath in absence of signs of congestive hemodynamics were included into this study.. Concentration of BNP in serum n the day of inclusion was significantly inversely related to results of 6-MWT, and positively related to left atrial dilation, to hospitalizations due to cardiovascular causes.. Measurement of BNP concentration in patients with AF allows to diagnose HF at early stages and to predict cardiovascular complications.

Topics: Aged; Atrial Fibrillation; Atrial Function, Left; Biomarkers; Early Diagnosis; Echocardiography, Three-Dimensional; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Patient Readmission; Predictive Value of Tests; Risk Factors; Thromboembolism

N-terminal pro brain natriuretic peptide (NT-proBNP) is closely related to risk stratification in many cardiovascular diseases. The objective of this study was to evaluate the association of NT-proBNP and impaired aortic elastic property in hypertensive patients.. One hundred fifty-five hypertensive patients without obvious cardiac dysfunction were included and divided in tertiles based on their NT-proBNP concentration. Eighty-six normotensive healthy volunteers were also enrolled as controls. All subjects underwent Doppler echocardiography to assess cardiac parameters and aortic distensibility index. Plasma NT-proBNP was measured by electrochemiluminescence.. The parameters of aortic elastic property were decreased and NT-proBNP was significantly increased in hypertensive patients compared with controls (all P<0.05). Among hypertensive patients, higher NT-proBNP tertiles were associated with larger systolic and diastolic aortic diameters, longer deceleration time of the E wave velocity (DT) and isovolumic relaxation time; decreased E/A ratio and more percent of diastolic dysfunction. The parameters of aortic elastic property showed stepwise decreases from the first tertiles to the third tertiles (P<0.05). Multiple linear regression analysis showed that concentrations of NT-proBNP were significantly correlated with age and impaired aortic distensibility.. NT-proBNP is a marker for impaired aortic elastic property in hypertensive patients. Measurement of NT-proBNP could be indicated in hypertensive patients for further risk stratification.

Topics: Aged; Aorta; Case-Control Studies; Echocardiography; Elasticity; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Chronic pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) and fibrosing lung diseases, and atrial fibrillation (AF), are prevalent in elderly people. The impact of cardiac co-morbidities in the elderly, where pulmonary function is impaired, cannot be ignored as they influence mortality. The relationship between the prevalence of AF and pulmonary function is unclear. The aim of this study was to evaluate this relationship in participants in a health check.. Subjects aged 40 or older (n = 2,917) who participated in a community-based annual health check in Takahata, Japan, from 2004 through to 2005, were enrolled in the study. We performed blood pressure measurements, blood sampling, electrocardiograms, and spirometry on these subjects.. The mean FEV(1) % predicted and FVC % predicted in AF subjects was significantly lower than in non-AF subjects. The prevalence of AF was higher in those subjects with airflow limitation or lung restriction than in those without. Furthermore, AF prevalence was higher in those subjects with severe airflow obstruction (FEV(1) %predicted < 50) than in those who had mild or moderate airflow obstruction (FEV(1) %predicted ≥ 50), although there was no difference between the prevalence of AF in subjects with 70≤ FVC %predicted <80 lung restriction and those with FVC %predicted <70. Multiple logistic regression analysis revealed that FEV(1) %predicted and FVC %predicted are independent risk factors for AF (independent of age, gender, left ventricular hypertrophy, and serum levels of B-type natriuretic peptide).. Impaired pulmonary function is an independent risk factor for AF in the Japanese general population.

Topics: Adult; Aged; Airway Obstruction; Atrial Fibrillation; C-Reactive Protein; Electrocardiography; Female; Forced Expiratory Volume; Humans; Hypertension; Inflammation; Japan; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prevalence; Risk Factors; Smoking; Spirometry; Vital Capacity

The production of brain natriuretic peptide (BNP) by ventricular cardiomyocytes is increased in patients with left ventricular hypertrophy (LVH). Increased plasma levels of BNP or of the inactive fragment NP-proBNP are associated with an increased cardiovascular risk. The measurement of plasma concentrations of these peptides may be useful for stratifying the cardiovascular risk of hypertensive patients, particularly if there is no electrocardiographic evidence for LVH.

Topics: Biomarkers; Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; Risk Factors; Sensitivity and Specificity

Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by physical examination is challenging, 24-hour urine collection and NT-proBNP levels are useful tools for guiding volume management and achieving sodium status targets.

Topics: Extracellular Space; Humans; Hypertension; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Nutritional Status; Peptide Fragments; Renin-Angiotensin System; Sodium; Sodium, Dietary

The European Society of Cardiology recently proposed a new algorithm "How to diagnose heart failure with normal ejection fraction". Central element of the diagnostic strategy is the demonstration of diastolic dysfunction, either by tissue Doppler-derived indices in first line, or in second line by a combination of elevated blood levels of natriuretic peptide with abnormal tissue Doppler findings. We thought to use this diagnostic flowchart in a population-based cohort of elderly women, in whom the prevalence of diastolic dysfunction and heart failure is believed to be high. The purpose was to evaluate the association of dyspnea with the presence of diastolic dysfunction.. The study cohort recruited from a cross-sectional follow-up examination of the SALIA cohort (study on the influence of air pollution on lung function, inflammation, and aging). Participants with cardiac or pulmonary disease were excluded, 291 participants formed the final study group (all women, age range 69 to 79 years, all in sinus rhythm, LV ejection fraction > 50%, LV enddiastolic volume index < 97 mL/m2). Quality of life was assessed by the Minnesota living with heart failure questionnaire, and actual symptoms by a structural questionnaire; the examination consisted of a physical examination, measurement of B-type natriuretic peptide, ECG and tissue Doppler echocardiography. Diastolic dysfunction was assumed when the E/E' ratio exceeded 15 as derived from tissue Doppler. In case, tissue Doppler yielded an E/E' ratio ranging from 8 to 15, additional non-invasive parameters had to be fulfilled: left atrial volume index > 40 ml/m2 body surface, or left ventricular mass index > 122 g/m2 body surface, or transmitral E/A ratio < 0.5 plus deceleration time > 280 ms, or blood level of brain natriuretic peptide (BNP) > 200 pg/mL.. The examinations were concordant with the presence of diastolic dysfunction in 122/291 participants (41.9%). The diagnosis based in 94% of cases on two criteria: in 50 cases on the criterion "E/E' ratio > 15", and in 65 cases on the criterion "15 > E/E'>8 and LV mass index > 122 g/m2". The participants with diastolic dysfunction had on average a higher body mass index, more frequent a history of arterial hypertension and of hospitalization for congestive heart failure, poorer quality of life, and higher BNP blood levels as compared to those participants without signs of diastolic dysfunction. The number of participants complaining exertional dyspnea, however, was similar distributed among the subgroups with and without signs of diastolic dysfunction (40.2 vs 40.8%; p = n.s). In a logistic regression model, the symptom dyspnea was best predicted by systolic pulmonary artery pressure, followed by left atrial volume index, BNP, and body mass index.. The demonstration of diastolic dysfunction showed only a poor association with the symptom dyspnea in a cohort of elderly women with otherwise normal systolic function. Additional structural or hemodynamic changes are necessary to "explain" the symptom dyspnea. It is unclear whether these additional factors are secondary to a more advanced stage of diastolic dysfunction, or are related to cardiovascular co-morbidities, or both.

Topics: Aged; Cohort Studies; Cross-Sectional Studies; Diastole; Dyspnea; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension; Natriuretic Peptide, Brain; Population Surveillance

In vitro studies suggest that phosphorylation of titin reduces myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP-activated protein kinase. Intracellular cGMP production is stimulated by B-type natriuretic peptide (BNP) and degraded by phosphodiesterases, including phosphodiesterase-5A. We hypothesized that a phosphodiesterase-5A inhibitor (sildenafil) alone or in combination with BNP would increase left ventricular diastolic distensibility by phosphorylating titin.. Eight elderly dogs with experimental hypertension and 4 young normal dogs underwent measurement of the end-diastolic pressure-volume relationship during caval occlusion at baseline, after sildenafil, and BNP infusion. To assess diastolic distensibility independently of load/extrinsic forces, the end-diastolic volume at a common end-diastolic pressure on the sequential end-diastolic pressure-volume relationships was measured (left ventricular capacitance). In a separate group of dogs (n=7 old hypertensive and 7 young normal), serial full-thickness left ventricular biopsies were harvested from the beating heart during identical infusions to measure myofilament protein phosphorylation. Plasma cGMP increased with sildenafil and further with BNP (7.31±2.37 to 26.9±10.3 to 70.3±8.1 pmol/mL; P<0.001). Left ventricular diastolic capacitance increased with sildenafil and further with BNP (51.4±16.9 to 53.7±16.8 to 60.0±19.4 mL; P<0.001). Changes were similar in old hypertensive and young normal dogs. There were no effects on phosphorylation of troponin I, troponin T, phospholamban, or myosin light chain-1 or -2. Titin phosphorylation increased with sildenafil and BNP, whereas titin-based cardiomyocyte stiffness decreased.. Short-term cGMP-enhancing treatment with sildenafil and BNP improves left ventricular diastolic distensibility in vivo, in part by phosphorylating titin.

Topics: Age Factors; Aging; Animals; Biopsy; Compliance; Connectin; Cyclic GMP; Diastole; Dogs; Hypertension; Muscle Proteins; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phosphorylation; Piperazines; Protein Kinases; Purines; Sarcomeres; Sildenafil Citrate; Sulfones; Vasodilator Agents; Ventricular Function, Left; Ventricular Pressure

The aim of this study was to evaluate early cardiac abnormalities in obese children by the conventional echocardiography and to verify whether N-terminal pro B-type natriuretic peptide (NT-proBNP) differ between obese and healthy children.. We started this study with 68 obese children and 35 healthy controls matched for age and sex. Body mass index (BMI) was calculated. Children with a BMI > or = 95th percentile were considered obese. Thirty children in the obese group were also diagnosed with metabolic syndrome, according to the International Diabetes Federation criteria. Standard echocardiographic study was performed on each patient and control subject. Diastolic filling parameters were evaluated using pulsed-wave tissue Doppler method. Blood samples were taken at 8 a.m. to study blood biochemistry tests, including insulin, lipids, glucose, and NT-proBNP. Serum NT-proBNP levels were measured by a solid-phase, enzyme-labeled chemiluminescent immunometric assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children with HOMA-IR > 3.16 were considered insulin-resistant.. There were diastolic filling abnormalities in obese children, as shown by a decreased mitral valve early filling (E) wave/late filling (A) ratio and a prolongation in E-wave deceleration time. The levels of NT-proBNP were not statistically different among the groups. The levels of NT-proBNP were not different between obese children with and without metabolic syndrome, those with and without hypertension, and those with and without insulin resistance, respectively.. Although there were diastolic filling abnormalities in obese children, their NT-proBNP levels were not different from healthy controls. It seems that there is no diagnostic value in NT-proBNP levels between obese children and healthy controls.

Topics: Adolescent; Biomarkers; Body Mass Index; Child; Diastole; Echocardiography; Female; Heart Diseases; Humans; Hypertension; Insulin Resistance; Male; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prevalence; Prospective Studies; Risk Factors

For the purpose of estimation of peculiarities of interrelation between endothelial dysfunction (ED) and myocardial dysfunction (MD) in elderly persons due to arterial hypertension (AH) 66 patients of elderly age with AH of II stage and 26 persons of similar age without cardiovascular diseases were examined. It is established, that development AH is accompanied by formation of a concentric hypertrophy and concentric remodelling of myocardium, diastolic and systolodiastolic myocardial dysfunction, its expressiveness is interfaced to severity of endothelial dysfunction. Progressing of ED is accompanied by infringements of lipids' metabolism, increasing of their peroxidation activity and decreasing in efficiency of anti-oxidation protection.

Topics: Age Factors; Aged; Biomarkers; Echocardiography, Doppler; Endothelium, Vascular; Heart Failure; Humans; Hypertension; Lipid Metabolism; Lipid Peroxidation; Natriuretic Peptide, Brain; Oxidative Stress; Risk Factors; Severity of Illness Index; Ventricular Remodeling

Left ventricular (LV) diastolic dysfunction and impairment of aortic elastic properties represent common sequelae of hypertension. We investigated the relationships of these cardiovascular adaptations with brain natriuretic peptide (BNP) levels in newly-diagnosed hypertension.. 200 consecutive hypertensives without LV hypertrophy (aged 52 years, 134 males, office BP=151.4/95.5 mmHg) underwent 24 hour ambulatory BP measurement as well as aortic stiffness and LV diastolic function assessment by means of carotid-femoral pulse wave velocity (c-f PWV) measurement and Tissue Doppler Imaging (TDI), respectively. Based on BNP values patients were classified into tertiles.. Hypertensives in the highest, compared to those in the lowest BNP tertile had significantly higher 24 h pulse pressure (by 6.2 mmHg, p=0.002), lower 24 h diastolic BP (by 5.7 mmHg, p=0.014), decreased Em/Am ratio (by 0.09, p=0.048) and increased c-f PWV (by 0.7 m/s, p=0.042). Moreover, hypertensives in the highest, compared with those in the lowest and the medium tertile of BNP, exhibited significantly lower Em (by 1.2 cm/s, p=0.001 and 1 cm/s, p=0.004, respectively) and higher E/Em ratio (by 1.3, p=0.018 and 1.3, p=0.014, respectively). BNP was significantly associated with E/Em ratio, 24 h pulse pressure and c-f PWV independently from age.. In hypertensives plasma BNP levels are associated not only with LV diastolic dysfunction but also with aortic stiffening. These findings suggest that BNP even within normal range constitutes a surrogate for cardiovascular functional impairment in the setting of essential hypertension without LV hypertrophy.

Topics: Adaptation, Physiological; Adult; Blood Flow Velocity; Blood Pressure Monitoring, Ambulatory; Carotid Arteries; Diastole; Echocardiography; Elasticity; Female; Femoral Artery; Humans; Hypertension; Hypertrophy, Left Ventricular; Laser-Doppler Flowmetry; Male; Middle Aged; Natriuretic Peptide, Brain; Pulsatile Flow; Ventricular Dysfunction, Left

Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH.. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records.. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03).. NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass.

Topics: Aged; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Factors

Patients with aortic valve sclerosis (AVS) have an increased risk of cardiovascular events. Patients with atherosclerotic renal artery stenosis (RAS) develop resistant hypertension and heart failure. We hypothesized AVS may be copresent with RAS in hypertensive patients.. Hypertensive patients with AVS (n = 167) underwent magnetic resonance (MR) angiography using nonenhanced steady-state free precession (SSFP) technique. More than 75% luminal narrowing in the proximal region of main renal artery was regarded as significant RAS. Peak aortic jet velocity was obtained by Doppler echocardiography. We measured brain natriuretic peptide (BNP), and estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation.. Unilateral or bilateral RAS was detected in 40 patients. AVS patients with RAS were older (78 +/- 6 vs. 74 +/- 8 years), and had higher levels of aortic jet velocity (162 +/- 4 vs. 144 +/- 3 cm/s), and lower levels of GFR (55 +/- 13 vs. 62 +/- 14 ml/min/1.73 m(2)) than those without RAS. Higher aortic jet velocity (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.09-2.31) and lower GFR (OR = 0.54, 95% CI = 0.33-0.38) were associated with the presence of RAS, after being adjusted for age, systolic blood pressure, and BNP.. RAS was detected in hypertensive patients with AVS, particularly in patients with higher aortic jet velocity and lower GFR. Higher aortic jet velocity and lower GRF may be useful as a potential indicator for those needing assessment of RAS for risk stratification and deserves further study.

Topics: Aged; Aortic Valve; Atherosclerosis; Diet; Female; Glomerular Filtration Rate; Heart Function Tests; Humans; Hypertension; Kidney Function Tests; Logistic Models; Magnetic Resonance Angiography; Male; Natriuretic Peptide, Brain; Odds Ratio; Renal Artery; Renal Artery Obstruction; Sclerosis; Ultrasonography

Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Factor VII; Factor VII Deficiency; Factor XI; Factor XI Deficiency; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypoprothrombinemias; Male; Natriuretic Peptide, Brain; Prognosis; Prothrombin; Risk

The main causes of congestive heart failure (CHF) are coronary artery disease (CAD) and arterial hypertension. Coronary artery calcification (CAC) evidencing coronary atherosclerosis may occur prior to clinical CAD. The aim of our study was to assess the association between CAC as a sign of subclinical CAD and CHF in a general unselected population.. Participants of the Heinz Nixdorf Recall Study without known CAD but with known CHF as defined by a physicians' diagnosis of CHF and dyspnea were identified. B-natriuretic peptide was measured and an exercise stress test was performed as possible. Cardiovascular risk factors and the EBCT-based CAC Agatston score were determined.. Those 105/4,230 subjects (2.5%) with CHF (age 65 +/- 7 years, 44% males), had higher brain natriuretic peptide (BNP) levels (median BNP 36.8 [16.5-70.1] vs. 17.6 [9.5-31.7] pg/ml, p<0.01) and lower exercise capacity (108.7 +/- 39.4 vs. 130.0 +/- 40.7 W, p<0.01) than those without. CAC in subjects with CHF was significantly higher than in those without (median CAC 64.7 [8.5-312.3] vs. 11.6 [0-109.8], p<0.01). In univariate analysis, CAC-burden after logarithmic transformation according to log(2)(CAC + 1) showed a significant association with the presence of CHF (odds ratio (OR) (95% CI): 1.16 (1.1-1.23), p<0.0001). Adjustment for age and sex (OR 1.11 (1.04-1.18), p<0.001), additional Framingham risk score (OR 1.09 (1.02-1.16), p = 0.015), and additional cardiovascular medication (OR 1.07 (0.998-1.14), p = 0.058) attenuated this association. Age, systolic blood pressure, antihypertensive medication and increased body mass index also remained significantly associated with presence of CHF in the full multivariate model.. The observed association between CAC and CHF in persons without clinically overt CAD is partly determined by risk factors that are involved in the natural history of both CAC and CHF. Whether CAC has a role to identify subjects at risk of future CHF remains to be determined using follow-up analyses.

Topics: Aged; Calcinosis; Calcium; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Exercise Test; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors

Diastolic dysfunction (DD) results in increased cardiovascular risk in hypertensives. We studied the performance of N-terminal probrain natriuretic peptide (NT-proBNP) in detecting DD.. 241 hypertensive patients admitted to cardiology polyclinics were included in this study. They were grouped according to the presence of DD. Group 1: Essential hypertensive patients without DD (n= 119); group 2: essential hypertensive patients with DD (n= 122). All underwent trans-thoracic echocardiography for the evaluation of transvalvular flow, morphology, left ventricular wall motion abnormalities and ejection fraction. NT-proBNP levels were measured by an electrochemiluminescence immunoassay.. The systolic blood pressure (BP) (mean+/-SD) was 140+/-12 mmHg in group 1 and 144+/-16 mmHg in group 2 (p=0.049), the diastolic BP (mean+/-SD) was 88+/-10 mmHg in group 1 and 90+/-14 mmHg in group 2 (p=0.043). The median (1st-3rd quartile) NT-proBNP level in group 2 was significantly higher than group 1 [121.05 (61.03-207.66) and 31.17 (17.07-54.09) pg/ml, respectively (p<0.001)]. In the receiver operating characteristics analysis, the area under the curve was 0.862 (95% CI 0.816-0.908). At the cut-off of 45 pg/ml, sensitivity was 86.9%, specificity was 62.4%, and at the cut-off 65 pg/ml, sensitivity was 74.6%, specificity was 83.8%.. Plasma NT-proBNP levels may be useful for identifying patients with DD and it is conceivable to use a cut-off level 65 pg/ml as a "rule in" test.

Topics: Diastole; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Ventricular Dysfunction, Left

The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients.. Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes.. LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM.. About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.

Topics: Adult; Albuminuria; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Ventricular Dysfunction, Left

N-terminal proBNP (NT-proBNP) is widely used as a diagnostic biomarker and for the risk stratification of patients with heart failure (HF). Its role in the evaluation of patients with essential hypertension (EHT) is less clear. We examined the relationship between NT-proBNP concentrations and various clinical characteristics in hypertensive patients without HF.. This study included 186 consecutive patients with EHT and no history of HF, ischemic heart disease, or atrial fibrillation. Single and multiple variable regression analyses were performed in search of clinical correlates of NT-proBNP concentrations.. In patients with EHT, median serum concentration of NT-proBNP was 73 pg/ml, and interquartile range (IQR) was 40-128 pg/ml. NT-proBNP was significantly higher (P<0.001) in women (87 pg/ml; IQR 55-137 pg/ml) than in men (52 pg/ml; IQR 24-115 pg/ml). Age (r=0.371, P<0.001), precordial QRS voltage (r=0.223, P<0.001), hemoglobin (Hgb) concentration, (r=-0.208, P=0.023) and estimated glomerular filtration rate (r=-0.139, P=0.044) were correlated with log-transformed NT-proBNP by multiple variable analysis. In men, age (r=0.453, P<0.001) and QRS voltage (r=0.283, P=0.004), and in women age (r=0.299, P=0.006), QRS voltage (r=0.212, P=0.019), Hgb (r=-0.182, P=0.049), and estimated glomerular filtration rate (r=-0.272, P=0.009) were correlated with serum concentrations of NT-proBNP.. Age, gender, Hgb, left ventricular hypertrophy and renal function were correlated with NT-proBNP in patients with EHT.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Electrocardiography; Female; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Statistics, Nonparametric

Hemodynamic parameters and natriuretic peptide levels were evaluated in cardiac hypertrophy produced by sequentially applied renovascular (RV) and deoxycorticosterone acetate-salt (DS) models of hypertension. We studied hypertensive rats by RV or DS treatment at 2 and 4 wk, as well as by the combination of 2 wk of each treatment in an inverse sequence: RV 2 wk/DS 2 wk (RV2/DS2) and DS 2 wk/RV 2 wk (DS2/RV2). The in vivo cardiac function, interstitial fibrosis, and synthesis and secretion of types A (ANP) and B (BNP) natriuretic peptides were monitored in hypertensive models compared with their corresponding sham (Sh2, Sh4). There were no differences in relaxation parameters among RV or DS groups and combined treatments. Left ventricular +dP/dt(max) increased only in RV4 (P < 0.01 vs. Sh4), and this increase was abolished in RV2/DS2. Interstitial collagen concentration increased after 4 wk in both RV4 and RV2/DS2 groups. Although there were no changes in collagen concentration in either DS2 or DS4 groups, clipping after 2 wk of DS (DS2/RV2) remarkably stimulated interstitial fibrosis (P < 0.01 vs. DS2). Plasma BNP increased in RV treatment at 4 wk (P < 0.001 vs. Sh4), but not in DS. Interestingly, RV applied after the 2 wk of DS treatment induced a marked increase in BNP levels (P < 0.001 vs. Sh4). In this regard, plasma BNP appears to be a reliable indicator of pressure overload. Our results suggest that the second stimulus of mechanical overload in combined models of hypertension determines the evolution of hypertrophy and synthesis and secretion of ANP and BNP.

Topics: Animals; Atrial Natriuretic Factor; Biomechanical Phenomena; Blood Pressure; Collagen; Desoxycorticosterone; Disease Models, Animal; Hypertension; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Natriuretic Peptides; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a multiple ligand receptor induced by oxidative stress. However, its role in chronic heart failure remains unknown.. The left ventricular (LV) expression of LOX-1 was examined in a salt-sensitive Dahl rat model of hypertension. Compared with controls, LOX-1 mRNA levels increased by 4.7-fold in the LV with hypertrophy, and by 32-fold in the LV with decreased systolic function. LV LOX-1 mRNA levels strongly correlated with the decrease in LV ejection fraction (EF) (r=-0.772), and with increases in the LV mRNA levels of B-type natriuretic peptide (r=0.814), monocyte chemoattractant protein-1 (r=0.943), transforming growth factor-beta(1) (r=0.936), and a macrophage marker, F4/80 (r=0.560). Serum levels of soluble LOX-1 were significantly elevated in patients with LV systolic dysfunction and hypertrophy, and significantly correlated with the decrease in EF (r=-0.495).. Marked increase in the LV expression of LOX-1 in failing hearts may contribute to increased serum levels, and might be involved in chronic inflammation during the development of heart failure.

Topics: Aged; Animals; Chemokine CCL2; Cross-Sectional Studies; Disease Models, Animal; Female; Heart Failure; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Rats; Rats, Inbred Dahl; RNA, Messenger; Scavenger Receptors, Class E; Ventricular Dysfunction, Left

Heart hypertrophy is a common cardiac complication of sustained arterial hypertension and is accompanied by an increased incidence of supraventricular tachyarrhythmia, such as atrial fibrillation and atrial flutter. Verapamil, a phenyalkylamine, belongs to the group of calcium channel antagonists (class IV antiarrhythmic drugs) and is frequently used for the management of supraventricular tachycardia and for ventricular rate control in atrial fibrillation and atrial flutter. Verapamil heart tissue and plasma levels after intraperitoneal dosing of spontaneously hypertensive and normotensive rats were investigated. Transcript expression of various ion channels, ion transporters, calcium handling, and cytoskeletal proteins by reverse transcriptase-polymerase chain reaction (RT-PCR) were further investigated. There was no difference in plasma pharmacokinetics when hypertensive and normotensive animals were compared. Strikingly, the tissue clearance of verapamil was highly significantly impaired in heart tissue of hypertensive animals. Gene expression analysis showed the repression of many cardiac-specific genes in spontaneously hypertensive but not in normotensive rats, therefore providing evidence for different modes of action in healthy and hypertrophic hearts. Verapamil heart tissue levels differed dramatically between normotensive and hypertensive rats and resulted in repression of many cardiac ion channels, ion transporters, and calcium handling proteins. A disturbed ion homeostasis induced by critical tissue levels of verapamil is therefore proposed as a molecular rational for its pro-arrhythmogenic activity. The observed changes can be a significant determinant of spatial electrophysiological heterogeneity, thereby contributing to increased conductance disturbance as observed with some patients.

Topics: Animals; Calcium Channel Blockers; Calcium Channels; Calmodulin; Calsequestrin; Cardiomegaly; Cytoskeletal Proteins; Down-Regulation; Gene Expression; Hypertension; Ion Channels; Male; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription Factors; Verapamil

To identify factors related to NT-proBNP levels in systemic sclerosis (SSc).. NT-proBNP was measured in 119 patients with SSc and 20 controls. Patients with transtricuspid gradient (TG) > or =36 mm Hg or > or =31 mmHg plus dyspnea were considered to have suspected systemic sclerosis-associated pulmonary arterial hypertension (SScPAH).. Increasing age, NYHA functional class, skin score, history of systemic arterial hypertension (SAH), anticentromere antibodies, diastolic dysfunction, reduced pulmonary diffusing capacity, and TG were positively associated with NT-proBNP. In multivariable linear regression, TG, age, and SAH were independently associated to NT-proBNP levels. An ROC curve analysis (with an area under the curve of 0.89, 95% CI: 0.83-0.95) suggested a cutoff of 157.8pg/mL to identify patients with suspected SScPAH, presenting a sensitivity of 100% (78.1-100) and specificity of 72.3% (62.3-80.5).. NT-proBNP levels are related to clinical and laboratory abnormalities in SSc. The results indicate that NT-proBNP may be a useful tool in the evaluation of SScPAH.

Topics: Adult; Age Factors; Case-Control Studies; Female; Humans; Hypertension; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Scleroderma, Systemic; Sensitivity and Specificity; Triglycerides

Obesity and hypertension are often comorbid, but the pathophysiologic mechanisms that link them are not fully understood. Natriuretic peptides might play a role in this association. The majority of studies show lower brain natriuretic peptide (BNP) concentrations as well as lower concentrations of the N-terminal of the prohormone (NT-proBNP) in obese than normal body mass index (BMI) adults and higher BNP concentrations in hypertensive than in normotensive individuals. In children, there are no studies examining the relations between NT-proBNP, BMI and blood pressure.. Ninety-six children, 24 obese/25 normal BMI boys, and 23 obese/24 normal BMI girls, aged 10-16 years, were studied. Plasma NT-proBNP was measured using electrochemiluminescence.. In males, NT-proBNP concentrations were lower in the obese than the normal BMI group but higher in the obese hypertensive than the obese normotensive group (p = 0.04). In addition, a significant positive correlation was noted between plasma NT-proBNP and blood pressure (p = 0.03) only in obese males. In females, no correlations were detected between NT-proBNP, BMI and systolic or diastolic blood pressure.. Longitudinal studies are needed to define the role of NT-proBNP as a screening biomarker in obese children, particularly males, to determine their risk for developing arterial hypertension.

Topics: Adolescent; Blood Pressure; Body Mass Index; Child; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Sex Factors

Topics: Biomarkers; Female; Heart Failure, Diastolic; Humans; Hypertension; Male; Matrix Metalloproteinase 1; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Prognosis; Reference Values; Risk Assessment; Stroke Volume; Tissue Inhibitor of Metalloproteinases

Chronic volume overload is very frequent in hemodialysis (HD) patients and is directly associated with hypertension, increased arterial stiffness, left ventricular hypertrophy (LVH), heart failure and ultimately with higher mortality and morbidity. One major issue is that presently there are very few comparative studies of the various methods (clinical, bioimpedance, inferior cava vein diameter (ICV) and Brain Natriuretic Peptide (NT-proBNP)) for volume status evaluation and their correlation with cardiovascular disease.. In 160 patients treated by chronic HD in our center, euvolemic according to clinical assessment, we performed evaluation of volume status through bioimpedance spectroscopy (BIS), ICV and NT-proBNP, as well as echocardiography, to estimate the left ventricle structure and function.. Despite appearing clinically euvolemic, severe fluid overload, as defined by a relative tissue hydration (RTH)--i.e. fluid overload over extracellular water ratio (FO/ECW)--above 15% was found in 25.6% of patients. Four categories of patients were considered according to pre-HD BP and BIS values. Forty-five percent of patients (group A) had a reasonable control of BP and volume (SBP < 150 mmHg and RTH < 15%), 29.3% (group B) were classified as hypertensive (SBP > 150 mmHg and RTH < 15%), 16.7% (group C) had high blood pressure and marked volume expansion, (SBP > 150 mmHg and RTH > 15%), while 9% (group D) had SBP < 150 mmHg despite RTH > 15%. Assuming that BIS is the most accurate and validated method to assess hydration status, we calculated the positive predictive value for ICV-based evaluation--18%, with a sensitivity of 67% and an important proportion of false negative cases (45%). NT-proBNP was even less accurate: PPV of only 26%, with a sensitivity of 60% and a specificity of only 45% and an extremely high proportion of false positive cases (73%). Group A patients had the best cardio-vascular profile: lowest LV mass and NT-proBNP levels.. Using multi-frequency body impedance spectroscopy, we found a large group of hypertensive and/or fluid-overloaded patients despite apparently being at "dry weight" on clinical evaluation and a marked discrepancy between clinical appearance and fluid status. Of the 4 different methods, assuming BCM "gold standard", there were major disagreements and discrepancies between the other three methodologies. BCM is a valuable and simple bed-side tool for the correct management of BP and risk stratification in HD patients as it allows for excellent discriminators of more abnormal cardiac and vascular profiles.

Topics: Biomarkers; Blood Pressure; Body Composition; Body Water; Echocardiography; Electric Impedance; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Vena Cava, Inferior; Ventricular Function, Left

B-type natriuretic peptide (BNP) decreases cardiac preload and hypertrophy. As such, synthetic BNP, nesiritide, was approved for the treatment of acutely decompensated heart failure. However, two problems limit its therapeutic potential. First, ensuing hypertension decreases urine output, and second, guanylyl cyclase-A (GC-A), the primary signaling receptor for BNP, is down-regulated in heart failure. Thus, alternative or chimeric natriuretic peptides maintaining the renal but lacking the vasorelaxation properties of BNP provide an alternative approach. Here, we examined the ability of single amino acid substitutions in the conserved 17-amino acid disulfide ring structure of human BNP to activate GC-A and guanylyl cyclase-B (GC-B), which is not reduced in heart failure. We hypothesized that substitution of highly conserved residues in BNP with highly conserved residues from a GC-B-specific peptide would yield BNP variants with increased and decreased potency for human GC-B and GC-A, respectively. Substitution of Leu for Arg13 (l-bnp) yielded a 5-fold more potent activator of GC-B and 7-fold less potent activator of GC-A compared with wild type. l-bnp also bound GC-A 4.5-fold less tightly than wild type. In contrast, substitution of Met for Ser21 (M-BNP) had no effect. A peptide containing both the Leu and Met substitutions behaved similarly to l-bnp. Meanwhile, wild-type and l-bnp bound the natriuretic peptide clearance receptor with similar affinities. These data indicate that Arg13 of BNP is a critical discriminator of binding to guanylyl cyclase-linked but not clearance natriuretic peptide receptors, supporting designer natriuretic peptides as an alternative to wild-type BNP for the treatment of heart failure.

Topics: Down-Regulation; Guanylate Cyclase; Heart Failure; Humans; Hypertension; Hypertrophy; Kidney; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptides; Receptors, Atrial Natriuretic Factor; Receptors, Peptide

The objective of this study was to assess a possible link between microalbuminuria (MA), a major risk factor of the cardiorenal syndrome and the brain natriuretic peptide (BNP), a marker of cardiac hypertrophy. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (weighing 220-250 g). Rats were randomized into four groups for 8 weeks: Sham, not treated; Bos, treated with bosentan; Cap, treated with captopril; Bos/Cap, treated with both drugs. Blood pressure, plasma BNP and transforming growth factor beta1 (TGF-β1) concentrations, microalbuminuria and creatininemia as well as cardiac mass, BNP, alpha- and beta-myosin heavy chain (MHC) gene expression and kidney histology were determined. Following stenosis, Sham rats developed hypertension (p < 0.001), an increase in BNP (p < 0.05) and TGF-β1 (p < 0.005) concentrations, creatinine levels (p < 0.001), and urinary albumin (p < 0.001). Under drug treatment, decreases in blood pressure (p < 0.001), creatinine levels (p < 0.05), plasma TGF-β1 (p < 0.005) and BNP (p < 0.05) concentrations, were concomitant with the absence of MA which was significantly correlated with reductions in cardiac mass (p < 0.05) and hypertrophy markers (BNP and β-MHC gene expression) (p < 0.005) as well as in renal fibrosis. These findings suggest a potential link between microalbuminuria evolution and BNP as well as a possible effect of microalbuminuria-lowering therapy on halting the progression, or even inducing the regression of cardiac hypertrophy.

Topics: Albuminuria; Animals; Blood Pressure; Cardiomegaly; Creatinine; Hypertension; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1

The blood pressure-lowering effect of the renin inhibitor aliskiren equals that of angiotensin-converting enzyme (ACE) inhibitors and angiotensin (Ang) II type 1 (AT1) receptor blockers. Whether aliskiren offers end-organ protection remains to be investigated. Here, we compared the cardiac effects of aliskiren, the AT1 receptor blocker irbesartan and the ACE inhibitor captopril in spontaneously hypertensive rats (SHR) at equi-hypotensive doses.. SHR were treated for 1-3 weeks with vehicle, aliskiren, captopril or irbesartan (100, 3 and 15 mg/kg per day, respectively) using an osmotic minipump, and compared to vehicle-treated Wistar-Kyoto (WKY) controls. All drugs lowered (but not normalized) mean arterial pressure in SHR equi-effectively, as monitored by radiotelemetry, without altering heart rate. All drugs also reduced the increased cardiomyocyte area in SHR, and tended to normalize the elevated brain natriuretic peptide plasma levels. In the Langendorff set-up, all drugs normalized the diminished endothelium-dependent vasodilator response to bradykinin in SHR. Moreover, aliskiren and irbesartan, but not captopril, decreased the enhanced coronary Ang II response in SHR. Aliskiren reduced plasma renin activity and the plasma and tissue angiotensin levels at 1 week of treatment; yet, after 3 weeks of aliskiren treatment only the cardiac angiotensin levels remained suppressed, whereas no tissue angiotensin reductions were seen with captopril or irbesartan.. For a given decrease in blood pressure, aliskiren improves coronary endothelial function and decreases cardiac hypertrophy in SHR to at least the same degree as ACE inhibition and AT1 receptor blockade. In addition, aliskiren diminishes the enhanced Ang II response in the coronary circulation of SHR and offers superior long-term cardiac angiotensin suppression.

Topics: Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Biphenyl Compounds; Blood Pressure; Captopril; Disease Models, Animal; Dose-Response Relationship, Drug; Fumarates; Heart; Heart Ventricles; Hypertension; Hypertrophy; Irbesartan; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Tetrazoles

Persistent atrial fibrillation (AF) leads to electrical, structural and neurohormonal remodelling of the atria, including increased plasma B-type natriuretic peptide (BNP) level.. To assess the clinical value of plasma BNP or NT-proBNP concentrations in patients with persistent AF measured before and after sinus rhythm restoration following direct-current cardioversion.. The study group consisted of 43 patients with persistent AF who underwent successful electrical cardioversion. The mean AF duration was 12.3 weeks. Patients in the study group had no symptoms of heart failure and they had preserved left ventricular systolic function. Blood samples were collected twice: 24 hours before and 24 hours after electrical cardioversion. Logistic regression analysis was used to assess the predictive value of BNP and NT-proBNP levels.. Baseline NT-proBNP and BNP levels were increased in patients with persistent AF (290.9 +/- 257.2 pg/mL and 148.4 +/- 111.4 pg/mL, respectively) compared to a matched control group without AF (47.8 +/- 80.6 pg/mL; p = 0.0001 and 74.9 +/- 81.7 pg/mL; p = 0.01). Plasma BNP level decreased 24 hours after cardioversion (from 148.4 +/- 111.4 to 106.4 +/- 74.7 pg/mL; p = 0.0045) whereas NT-proBNP level did not (from 290.9 +/- 257.2 to 262.7 +/- 185.6 pg/mL; NS). During an 18-month follow-up period, 21 (49%) patients remained in sinus rhythm. Neither baseline plasma BNP nor NT-proBNP level predicted sinus rhythm maintenance.. NT-proBNP and BNP plasma levels are increased in patients with persistent AF. Conversion to sinus rhythm is associated with a significant decrease in plasma BNP but not NT-proBNP level. Baseline BNP and NT-proBNP levels do not predict long-term sinus rhythm maintenance.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Chronic Disease; Diabetes Complications; Echocardiography; Electric Countershock; Female; Follow-Up Studies; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Young Adult

An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in microg/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH(2))(5), Tyr(Me)(2), Orn(8)]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregulated by ovariectomy, increased in response to genistein. In SHRs or SD rats, this effect was blocked by OTA or ICI-182780 administration. The OTR was mainly localized in microvessels expressing the CD31 marker and colocalized with endothelial nitric oxide synthase. In SHRs, the genistein-stimulated OTR increases were associated with improved fractional shortening, decreased blood pressure (12 mmHg), decreased heart weight-to-body weight ratio, decreased fibrosis, and lowered brain natriuretic peptide in the LV. The prominent finding of the study is the detrimental effect of OTA treatment on the LV of SHRs. OTA treatment of OVX SHRs resulted in a dramatic worsening of ejection fractions and an augmented fibrosis. In conclusion, these results demonstrate that cardiac OTRs are involved in the regulation of cardiac function of OVX SHRs. The decreases of OTRs may contribute to cardiac pathology following menopause.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol; Estrogen Antagonists; Female; Fibrosis; Fulvestrant; Genistein; Hypertension; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Ovariectomy; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Receptors, Estrogen; Receptors, Oxytocin; RNA, Messenger; Vasotocin; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

Angiotensin receptor blockers (ARBs) are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI) in comparison with calcium channel blockers (CCBs) alone in hypertensive patients with metabolic syndrome (MetS). A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP) significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to improve subclinical atherosclerosis of patients with MetS.

Topics: Ankle; Antihypertensive Agents; Arteries; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Carotid Arteries; Female; Humans; Hypertension; Kidney; Male; Metabolic Syndrome; Middle Aged; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Tetrazoles; Ultrasonography

In the early identification of cardiovascular risk, it is essential to establish a biological marker for cardiac complications that is comparable to albuminuria for nephropathy. We tested the hypothesis that N-terminal pro-brain natriuretic peptide (NT-proBNP) might be a marker for silent myocardial ischaemia in diabetes.. In forty consecutively recruited subjects without evident coronary artery disease, serum NT-proBNP was measured together with multi-slice computed tomography. With patients suspected of having significant coronary artery stenosis by multi-slice computed tomography, coronary angiography was performed. Silent myocardial ischaemia was defined as the presence of significant coronary artery stenosis with more than 50% luminal narrowing by angiography.. Thirteen patients (32.5%) had silent myocardial ischaemia. NT-proBNP levels were significantly higher in these patients (181.1 ± 43.8 versus 55.2 ± 9.7 pg/mL, p < 0.005) but HbA(1c), lipid profiles, and creatinine were similar in the two groups. Moreover, log NT-proBNP was identified as an independent predictor of silent myocardial ischaemia (R(2) = 0.502, p < 0.05) after adjustment for HbA(1c), creatinine, albuminuria, hypertension, hyperlipidaemia, or smoking. After stratifying patients by NT-proBNP, the upper tertile compared to the lowest tertile was significantly associated with silent myocardial ischaemia (odds ratio: 26.7, p < 0.05). Receiver operation characteristics analysis with a cut-off value of 52 pg/mL showed 92% sensitivity and 75% specificity for predicting silent myocardial ischaemia (positive predictive value 64.7%, negative predictive value 94.3%).. The outstandingly high negative predictive value of NT-proBNP enables us to focus on diabetic patients with occult coronary disease, independently of microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

The extracellular matrix (ECM) is a major determinant of the structural integrity and functional properties of the myocardium in common pathological conditions, and changes in vasculature contribute to cardiac dysfunction. Collagen (Col) XV is preferentially expressed in the ECM of cardiac muscle and microvessels.. We aimed to characterize the ECM, cardiovascular function and responses to elevated cardiovascular load in mice lacking Col XV (Col15a1(-/-)) to define its functional role in the vasculature and in age- and hypertension-associated myocardial remodeling.. Cardiac structure and vasculature were analyzed by light and electron microscopy. Cardiac function, intraarterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor. Under basal conditions, lack of Col XV resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and age-dependent defects in heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of nonfibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes. In response to experimental hypertension, Col15a1 gene expression was increased in the left ventricle of wild-type mice, and mRNA expression of natriuretic peptides (ANP and BNP) and ECM modeling were abnormal in Col15a1(-/-) mice.. Col XV is necessary for ECM organization in the heart, and for the structure and functions of microvessels. Col XV deficiency leads to a complex cardiac phenotype and predisposes the subject to pathological responses under cardiac stress.

Topics: Age Factors; Aging; Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomyopathies; Collagen; Coronary Circulation; Disease Models, Animal; Echocardiography; Elasticity; Enzyme Inhibitors; Extracellular Matrix; Female; Gene Expression Profiling; Gene Expression Regulation; Genotype; Heart Ventricles; Hemodynamics; Hypertension; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Microcirculation; Microscopy, Electron; Microscopy, Video; Myocardium; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Phenotype; Polymerase Chain Reaction; RNA, Messenger; Telemetry; Ventricular Remodeling

To investigate the effect of metoprolol succinate sustained-release tablets on cardiac function, serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in elderly hypertensive patients and its relation with pulse pressure (PP).. A total of 330 elderly hypertensive patients with chronic heart failure receiving basic therapy were included. Before initiation and 3 months after the maximal tolerated dose of metoprolol succinate sustained-release tablets, the parameters of blood pressure, clinical features, radionuclide ventriculographic and laboratory findings of the patients were analyzed.. As the PP was elevated, the serum levels of VEGF, hs-CRP and BNP increased and the cardiac systolic and diastolic functions decreased. In patients with PP of 59-68 mmHg and > 68 mmHg, 3 months of treatment with the tablets caused significantly increased LVEF by (3.32 ± 2.35)% and (4.12 ± 3.05)% and LVPER by 0.37 ± 0.26 and 0.53 ± 0.37, respectively; PP were decreased by 8.2 ± 3.1 mmHg and 9.4 ± 4.3 mmHg and VEGF by 18.39 ± 8.43 pg/ml and 26.79 ± 14.32 pg/ml, respectively. The treatment also resulted in lowered hs-CRP and BNP in these patients by 0.26 ± 0.13 mg/L and 0.33 ± 0.16 mg/L and by 140.36 ± 68.62 ng/L and 155.39 ± 73.58 ng/L, respectively.. Obvious elevation of PP is associated with a better response to metoprolol succinate sustained-release tablets in elderly hypertensive patients with chronic heart failure, and 3 months of treatment with the tablets can significantly improve the cardiac function and lower the levels of VEGF, hs-CRP and BNP in these patients.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Blood Pressure; C-Reactive Protein; Chronic Disease; Delayed-Action Preparations; Female; Heart Failure; Humans; Hypertension; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Vascular Endothelial Growth Factor A

Large-scale genome-wide association studies (GWAS) have been successful in identifying genes that contribute to common diseases and phenotypes. A GWAS of hypertension-related phenotypes in a Japanese population was conducted in the current study.. A total of 936 participants were recruited from the Suita Study and a GWAS with 538,732 single nucleotide polymorphisms (SNP) was performed. The phenotypes included were systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), waist-to-hip ratio (WHR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma brain natriuretic peptide (BNP) concentration and alcohol consumption (AC). The SNP exceeding the genome-wide significance level were subjected to subsequent association studies using samples available from the Suita Study and Nomura Study. There is no master gene in the Japanese population that profoundly affects SBP, DBP, BMI, WHR, PRA and PAC. AC was influenced by the functional polymorphism in ALDH2, which affected BP levels in men. The BNP concentration was influenced by a polymorphism in the 3' region of the gene encoding for BNP. However, this polymorphism did not influence blood pressure (BP). Six SNP were identified to be associated with hypertension in both the Suita and Nomura studies.. Although several candidate SNP relevant to hypertension and those influencing AC and BNP were identified, our middle-sized GWAS indicated that there is no master gene in Japanese people that profoundly affects BP-related phenotypes.

Topics: Adult; Aged; Alcohol Drinking; Aldosterone; Asian People; Biomarkers; Blood Pressure; Body Mass Index; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Hypertension; Japan; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Renin; Risk Assessment; Risk Factors; Waist-Hip Ratio

Topics: Animals; Atrial Natriuretic Factor; Calcineurin; Heart Failure; Humans; Hypertension; Models, Animal; Myocytes, Cardiac; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Rats; Recombinant Fusion Proteins; Signal Transduction; Sodium-Hydrogen Exchangers; Ventricular Remodeling

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renal Insufficiency

To investigate the relationship between B-type natriuretic peptides (BNP) and subclinical target organ damage in essential hypertensive (EH) patients.. A total of 317 EH patients were divided into 3 groups according to BNP levels, namely normal (BNP<600 ng/L) group (n=102), moderate (600-883.5 ng/L) group (n=116), and elevated BNP (>883.5 ng/L) group (n=99). The blood pressure, left ventricular mass index (LVMI), the intima media thickness (IMT) of the common carotid artery, the plaque size in the coronary artery (CS) and microalbuminuria levels were analyzed in these patients.. The EH patients with moderate and elevated BNP showed significantly higher LVMI, IMT, CS and microalbuminuria levels than those with normal BNP level (LVMI: 102.8∓23.12 and 123.9∓26.47 vs 91.09∓18.71 g/m2; IMT: 0.95∓0.32 and 1.16∓0.37 vs 0.84∓0.28 mm; microalbuminuria: 31.36∓20.55 and 36.73∓22.07 vs 23.21∓18.68, P<0.01). After adjustment, BNP was positively correlated to LVMI, IMT, CS and microalbuminuria level (r=0.45, 0.43, 0.39 and 0.41, respectively, P<0.01). Multivariate logistic regression analysis showed that age, systolic blood pressure, BNP, FPG, and microalbuminuria, LDL-C, and BMI were all related to the occurrence of subclinical target organ damages.. BNP is positively correlated to subclinical target organs damages in EH patients.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Carotid Artery, Common; Carotid Intima-Media Thickness; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain

Amlodipine, a calcium channel blocker (CCB), is one of the most common antihypertensive medicines in Japan. We evaluated whether the calcium channel blocker confers cardiac protection through the renin-angiotensin-aldosterone system in male stroke-prone spontaneously hypertensive rats (SHR-SP).. Fifteen week-old rats were divided into 2 groups: amlodipine group (3 mg/kg/day, n = 5) and control group (n = 5).. The CCB lowered systolic blood pressure significantly (P < 0.05). Plasma aldosterone concentration in the amlodipine group was remarkably lower than in the control group (P < 0.05), but plasma renin activity and plasma angiotensin II concentration were not different between the two groups. The CCB also suppressed the mRNA expression of brain natriuretic peptide, transforming growth factor-β₁, and fibronectin extracted from the left ventricle.. These results suggest that amlodipine attenuates cardiac damage by lowering plasma aldosterone concentration in hypertensive rats with developing arteriosclerosis.

Topics: Aldosterone; Amlodipine; Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cardiotonic Agents; Fibronectins; Gene Expression Regulation; Heart; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Renin; Renin-Angiotensin System; Transforming Growth Factor beta

Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.. We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048).. Serum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.

Topics: Adipokines; Aged; Biomarkers; Case-Control Studies; Chitinase-3-Like Protein 1; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Glomerular Filtration Rate; Glycoproteins; Heart Atria; Heart Failure; Hospitalization; Humans; Hypertension; Inflammation; Lectins; Male; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Severity of Illness Index; Sodium; Uric Acid

Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63-203.40) pg/mL. In patients with MAU (ACR ≥20mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49-4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39-7.68) and death (OR, 4.63; 95%CI, 1.44-14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP.

Topics: Aged; Albuminuria; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hypertension; Irbesartan; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries; Risk Factors; Stroke; Tetrazoles

To investigate the relation between brain natriuretic peptide (BNP) rs198388 polymorphism and the susceptibility of essential hypertension in Han population of Hunan.. A total of 567 patients with hypertension (the hypertension group) and 555 healthy volunteers (the control group) were enrolled. Gender, age, smoking and drinking history of the 2 groups were not significantly different. Blood pressure was measured in the 2 groups. After fasting for 12 h or more, blood glucose, total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol were measured. DNA polymorphism analysis was done by polymerase chain reaction-restriction fragment length polymorphism method, and genotype was determined by agarose gel electrophoresis.. The GG, GA, and AA genotypes were detected.The frequencies of GA and AA genotypes and A allele were significantly lower in the hypertension group (GA and AA:12.3%;A:6.9%) than those in the control group (GA and AA:18.4%; A:9.7%; P=0.009, and P=0.014, respectively).. BNP rs198388 polymorphism may be associated with essential hypertension in Han people in Hunan. Carrying rs198388 GA and AA genotypes and A allele may be the reason for low risk of hypertension.

Topics: Adult; Aged; Base Sequence; Case-Control Studies; China; Female; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Male; Middle Aged; Molecular Sequence Data; Natriuretic Peptide, Brain; Polymorphism, Genetic

We examined 55 consecutive patients successfully treated with primary percutaneous coronary intervention (PCI) for a first acute myocardial infarction with left ventricular (LV) systolic dysfunction. In all patients we performed echocardiographic examination, dosage of plasma brain natriuretic peptide, serum carboxy-terminal propeptide and telopeptide of procollagen type I and amino-terminal propeptide of procollagen type III at days 1 and 3, and at 1 and 6 months after index infarction. The hypertensive patients (group 1; n=30) differed for higher baseline blood pressure (133+/-4 mm Hg vs 118+/-4 mm Hg; P=0.03), greater LV mass index (108+/-5 vs 94+/-4 g m(-2), P=0.03) and lower mitral E/A wave peak (0.8+/-0.06 vs 1.1+/-0.12, P=0.02) with respect to non-hypertensive patients (group 2; n=25). From day 1 to month 6 carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III increased (P<0.005 and P<0.05, respectively) in both groups, whereas carboxy-terminal telopeptide of procollagen type I increased from day 1 to day 3 (P<0.01 in both groups, respectively) and then decreased from day 3 to month 6 (P<0.01 and P<0.05 in both groups, respectively). From day 1, brain natriuretic peptide decreased in both groups (P<0.005). There was no significant difference between the two groups in values of procollagens and natriuretic peptide. Finally, LV diastolic volume and function at 6 months were similar in the two groups. Thus, in patients with reperfused acute myocardial infarction and LV dysfunction, antecedent hypertension was not associated with a different pattern of serum procollagen release and ventricular remodelling at 6 months of follow-up.

Topics: Adrenergic beta-Antagonists; Aged; Angiography; Collagen Type I; Collagen Type III; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Procollagen; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

This study investigated plasma brain natriuretic peptide (BNP) levels in normotensive and hypertensive patients with suspected coronary artery disease during radionuclide pharmacological stress testing. Twenty-seven normotensive patients (15 males, aged 63.0+/-4.5 years and 12 females, aged 63.0+/-4.1 years) and 38 essential hypertensive patients (25 males, aged 63.3+/-3.3 years and 13 females, aged 64.6+/-2.6 years) with chest pain and exercise stress testing inconclusive for coronary artery disease underwent myocardial perfusion single-photon emission computed tomography (SPECT) using adenosine infusion. SPECT identified patients without (16 normotensive and 22 hypertensive) and patients with (11 normotensive and 16 hypertensive) transient perfusion defects. Basal BNP levels in normotensive patients without transient myocardial ischemia (3.1+/-1.2 fmol/ml) were significantly (P<0.01) lower than those observed in normotensive patients with transient ischemia (8.2+/-1.2 fmol/ml), whereas BNP levels in hypertensive patients without transient ischemia (8.2+/-1.0 fmol/ml) did not significantly differ from those in hypertensive patients with transient ischemia (8.1+/-2.0 fmol/ml). No significant difference was found in BNP levels between males or females either in normotensive or hypertensive patients without or with ischemia. Adenosine infusion did not significantly change BNP levels in any subject group without or with myocardial perfusion defects. Our findings show that increases in BNP allow early detection of myocardial ischemia in normotensive patients, but not in hypertensive patients with suspected coronary artery disease. Adenosine-induced myocardial ischemia does not affect BNP production already activated by coronary artery disease in normotensive patients and by hemodynamic changes in hypertensive patients.

Topics: Adenosine; Aged; Coronary Artery Disease; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Tomography, Emission-Computed, Single-Photon

Arterial stiffness increases with age and contributes to the pathogenesis of systolic hypertension and cardiovascular disease in the elderly. Knowledge about the pathophysiological processes that determine arterial stiffness may help guide therapeutic approaches.. We related 7 circulating biomarkers representing distinct biological pathways (C-reactive protein, aldosterone-to-renin ratio, N-terminal proatrial natriuretic peptide and B-type natriuretic peptide, plasminogen activator inhibitor-1, fibrinogen, and homocysteine) to 5 vascular function measures (central pulse pressure, carotid-femoral pulse-wave velocity, mean arterial pressure, forward pressure wave amplitude [all measures of conduit artery stiffness], and augmented pressure, an indicator of wave reflection) in 2000 Framingham Offspring Study participants (mean age, 61 years; 55% women). Tonometry measures were obtained on average 3 years after the biomarkers were measured. In multivariable linear regression models adjusting for covariates, the biomarker panel was significantly associated with all 5 vascular measures (P<0.003 for all). On backward elimination, the aldosterone-to-renin ratio was positively associated with each stiffness measure (P< or =0.002 for all). In addition, C-reactive protein was positively related to augmented pressure (P=0.0003), whereas plasminogen activator inhibitor-1 was positively associated with mean arterial pressure (P=0.003), central pulse pressure (P=0.001), and forward pressure wave (P=0.01).. Our cross-sectional data on a community-based sample suggest a distinctive pattern of positive associations of biomarkers of renin-angiotensin-aldosterone system activation with pan-arterial vascular stiffness, plasminogen activator inhibitor-1 with central vascular stiffness indices, and C-reactive protein with wave reflection. These observations support the notion of differential influences of biological pathways on vascular stiffness measures.

Topics: Aldosterone; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; C-Reactive Protein; Cross-Sectional Studies; Female; Fibrinogen; Homocysteine; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Plasminogen Activator Inhibitor 1; Protein Precursors; Renin; Renin-Angiotensin System; Risk Factors

Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in cardiomyocytes and has been shown to be increased in hypertensive patients. The objective of this study was to evaluate the association of cardiotrophin-1 with heart failure (HF) in hypertensive patients and its usefulness as a biomarker of stage C heart failure. Hypertensive patients without cardiac abnormalities (stage A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with left ventricular hypertrophy and clinical manifestations of chronic heart failure (stage C, n = 39) were studied. Plasma cardiotrophin-1 was measured by an enzyme-linked inmunosorbent assay. Plasma cardiotrophin-1 progressively increased (P < 0.001), along with progression of heart failure stages, in hypertensive patients. Plasma cardiotrophin-1 was directly (r = 0.416, P < 0.001) and inversely (r = 0.263, P < 0.01) correlated with left ventricular (LV) mass index and ejection fraction, respectively, in all hypertensive patients. These associations were independent of a number of potential confounding factors. Receiver operating characteristic curves showed that a cut-off of 48.72 fmol/ml for cardiotrophin-1 provided higher sensitivity for diagnosing stage C heart failure than a cut-off of 375.54 pg/ml for amino-terminal probrain natriuretic peptide (NT-proBNP) (80% vs. 72%). Sixty-four percent of stage C hypertensive patients with NT-proBNP values below 375.54 pg/ml value exhibited cardiotrophin-1 values above 49.16 fmol/ml. These findings indicate that plasma cardiotrophin-1 is associated with progression of heart failure in hypertensive patients. Cardiotrophin-1 measurement may provide additional information to that afforded by NT-proBNP to diagnose stage C heart failure in these patients.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Cytokines; Female; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ventricular Dysfunction, Left

To investigate plasma brain natriuretic peptide (BNP) concentrations in association with blood pressure (BP) at baseline and after antihypertensive drug treatment.. We prospectively examined 186 individuals with newly diagnosed essential hypertension without target organ damage, whose mean age was 48.7 +/- 10.9 years. Treatment initiation began with irbesartan 150 mg/day and was doubled at 4 weeks in cases of inadequate BP control. If indicated, at 8-week-follow-up hydrochlorothiazide 12.5 mg alone or with amlodipine 5-10 mg was added. BNP levels were measured at baseline and after 3 months of antihypertensive treatment.. At baseline plasma BNP levels were found to be related to systolic BP (r = 0.27, P < 0.001), independent of age, sex, smoking status, BMI and left ventricular mass index estimated by echocardiography (beta = 11.81, SE = 3.82, P = 0.002). Additionally, higher BNP concentrations were observed in patients with stage 2 hypertension compared with those with stage 1 (median 38.9 vs. 29.9 pg/ml, P = 0.022). Multivariate analysis showed a positive association between BNP and systolic BP variability (beta = 0.03, SE = 0.01, P = 0.034). At follow-up, 64.7% of the participants who had achieved BP control showed decreased BNP levels in contrast to those with poor BP control (median change -14.5 vs. -1.3 and median range from -34.4 to -4.4 vs. -9.6 to 10.9, respectively, P < 0.001).. In this hypertensive population, increased BNP concentrations are associated with higher BP levels and systolic BP variability. The fall of BNP observed in those who achieved BP control indicates that BNP could be used as a biochemical marker of effective BP control and target organ protection.

Topics: Adult; Antihypertensive Agents; Biomarkers; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension; Linkage Disequilibrium; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Polymorphism, Single Nucleotide

The role of natriuretic peptides in the screening of left ventricular dysfunction is still unclear. The aim of this study was to assess the usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement in asymptomatic patients at high risk of developing left ventricular dysfunction.. One hundred and thirty-four consecutive ambulatory patients (mean age 56.1 +/- 7 years) were studied and selected on the basis of a history of hypertension of at least 5 years. Systolic dysfunction was defined as an ejection fraction of 45% or less. Statistical analysis was performed by both parametric and nonparametric approaches. Diagnostic accuracy was evaluated by receiver operating characteristic analysis.. Echocardiography showed normal left ventricular function in 40 patients, diastolic dysfunction in 80 patients and systolic dysfunction in 14 patients. NT-proBNP levels were significantly higher in patients with systolic dysfunction (356.1 +/- 294.8 vs. 85.2 +/- 85.8 pg/ml; P < 0.05). Receiver operating characteristic analysis showed a high value of the area under the curve (0.89) for the detection of systolic dysfunction with a sensitivity of 83% and a specificity of 80% for a cut-off value of 114 pg/ml and with a negative predictive value of 0.98.. In asymptomatic patients at high risk for heart failure because of a history of hypertension, the measurement of NT-proBNP levels may represent a useful screening test for left ventricular systolic dysfunction. Therefore, more expensive examinations, such as echocardiography, may be restricted only to patients with higher NT-proBNP levels.

Topics: Biomarkers; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Risk Assessment; ROC Curve; Sensitivity and Specificity; Stroke Volume; Up-Regulation; Ventricular Dysfunction, Left

Topics: Biomarkers; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Natriuretic Peptide, Brain; Peptide Fragments; Renal Plasma Flow

This study sought to compare the renal clearance mechanisms of B-type natriuretic peptide (BNP) and amino terminal pro-B-type natriuretic peptide (NT-proBNP).. The small molecular weight proteins (SMWPs) BNP and NT-proBNP both inversely correlate with glomerular filtration rate (GFR). Whether this association is causal or confounding is unknown and has been the basis of widespread speculation.. We combined measurements of BNP and NT-proBNP concentrations in the renal arteries and veins of 165 subjects undergoing renal arteriography with invasive renal plasma flow (RPF) measurements and echocardiography. Fractional extraction (FE) of BNP and NT-proBNP was computed.. The BNP and NT-proBNP concentrations correlated similarly to GFR (r = -0.35 and r = -0.30, respectively; p < 0.001 for both) but the NT-proBNP/BNP serum ratio was negatively associated with GFR (r = -0.21, p = 0.008). Median FE(BNP) was 0.21 (interquartile range [IQR] 0.16 to 0.22) for left and 0.22 (IQR 0.17 to 0.29) for right kidneys. Median FE(NT-proBNP) was 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FE(BNP) correlated with GFR (left: r = 0.26, p = 0.008; right: r = 0.21, p = 0.03) as did FE(NT-proBNP) (left: r = 0.25, p = 0.005; right: r = 0.20, p = 0.02). Although FE(BNP) and FE(NT-proBNP) correlated strongly with each other (left: r = 0.66; right: r = 0.60; p < 0.001 for both), left and right FE(NT-proBNP/BNP) ratios were not influenced by GFR (r = 0.10, p = 0.30 and r = 0.08, p = 0.43, respectively). Multivariate analyses confirmed that FE was not independently associated with BNP or NT-proBNP concentrations.. Contrary to widespread belief (but in line with the renal physiology of SMWP), BNP and NT-proBNP are equally dependent on renal function for their clearance.

Topics: Biomarkers; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiography; Renal Artery; Renal Plasma Flow

1. It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2. In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3. The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and β-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52% vs TAC, respectively), accompanied by significant inhibition of nuclear factor-κB and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats.

Topics: Animals; Antioxidants; Atrial Natriuretic Factor; Catalase; Catechin; Disease Models, Animal; DNA, Mitochondrial; Electron Transport Chain Complex Proteins; Enzyme Activation; Glutathione Peroxidase; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Malondialdehyde; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mitochondria, Heart; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinases; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Transcription Factor AP-1

We investigated the effects of iptakalim, a new ATP-sensitive potassium channel (K(ATP)) opener providing endothelial protection, on the progression of cardiac hypertrophy to failure in a rat model of pressure overloading caused by abdominal aortic banding (AAB). Endothelial dysfunction is central to cardiac hypertrophy and failure induced by pressure overload. It would be useful to clarify whether iptakalim could prevent this.. The effects of pressure overload were assessed in male Sprague-Dawley rats 6 weeks after AAB using progression of cardiac hypertrophy to heart failure as the endpoint. The AAB-treated rats had significantly elevated blood pressure, systolic and diastolic cardiac dysfunction, evidence of left ventricular hypertrophy (LVH), and transition to heart failure. LVH was characterized by increases in the ratios of heart and left ventricular weights to body weight, increased myocyte cross-sectional areas, myocardial and perivascular fibrosis, and elevated cardiac hydroxyproline. These could be prevented by treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg for 6 weeks. Progression to cardiac failure, demonstrated by increases in relative lung and right ventricular weights, cardiac function disorders and overexpression of atrial and B-type natriuretic peptide mRNA, could also be prevented. The downregulated nitric oxide signalling system was enhanced, whereas the upregulated endothelin signalling system was inhibited, resulting in normalization of the balance between these two systems.. Iptakalim protected the endothelium and prevented progression of cardiac hypertrophy to failure induced by a pressure overload.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Fibrosis; Heart Failure; Heart Rate; Hydroxyproline; Hypertension; Hypertrophy, Left Ventricular; KATP Channels; Male; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Propylamines; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Ventricular Remodeling

Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF).. Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke.. One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p<0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543).. Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

Topics: Aged; Atrial Fibrillation; Brain Ischemia; Diabetes Complications; Female; Heart Failure; Humans; Hyperlipidemias; Hypertension; Linear Models; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Risk Factors; Smoking; Stroke

Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR) and several cardio-vascular risk factors. Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. The aim of this study was to look for possible correlations between SDB, IR, heart structure and function indexes and NT-proBNP levels in MO female subjects.. Cross-sectional study involving 110 MO (44.5+/-0.7 kg m(-2)) apparently healthy, young (37.8+/-1.0 y.o.) female patients. NT-proBNP was measured using an ELISA kit (Roche). Echo-cardiograms were performed to quantify left ventricular ejection fraction values (LVEF), cardiac output (CO), left ventricular mass (LVM), left atria size (LA) and left ventricular filling pressures (the E/Em ratio). The Berlin Questionnaire (BQ) was used to assess the risk of SDB. IR and sensitivity were assessed using the HOMA index and adiponectin measurements, respectively.. All patients had a normal LVEF (>50%). Hypertension and Type 2 diabetes mellitus prevalences were 34.5 and 4.5% (respectively). Log-transformed NT-proBNP levels correlated with BQ categories (P<0.0005), creatinine (P<0.001), age (P<0.05), LVM (P<0.001), CO (P<0.001), LA (P<0.0005) and E/Em (P<0.01). NT-proBNP levels, LVD and LVM increased significantly along with BQ scores (P<0.0001). Stepwise multiple regression analysis identified BQ and log-transformed HOMA as independent variables predicting as much as 48.0% of log-transformed NT-proBNP's variability (dependent variable).. NT-proBNP levels are independently predicted by SDB and IR in asymptomatic MO women. Additionally, SDB worsens along with LVH and diastolic dysfunction. Larger prospective studies are warranted.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Linear Models; Natriuretic Peptide, Brain; Obesity, Morbid; Peptide Fragments; Predictive Value of Tests; Prevalence; Risk Factors; Sleep Apnea Syndromes

Topics: Diabetic Nephropathies; Dyspnea; Female; Humans; Hypertension; Lung; Lymphatic Vessels; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Radiography, Thoracic

The aim of our study was to determine concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with cirrhosis, thereby describing the hemodynamic and cardiac profiles to verify the existence of cirrhotic cardiomyopathy.. Clinical data, NT-proBNP levels, echocardiography, and right heart hemodynamic measurements were performed on all patients undergoing liver transplantation for cirrhosis.. Our patients showed a hyperdynamic circulation with elevated left-sided pressures despite high cardiac outputs. This observation suggested abnormalities in left ventricular diastolic compliance. We verified these results, because our cohort showed a significant left ventricular mass index and, consequently, diastolic dysfunction. Mean NT-proBNP levels were high. The great expansion of central volume may explain these results and the later development of left ventricular hypertrophy.. We concluded that elevated concentrations of NT-proBNP indicated the presence of hyperdynamic syndrome and cardiac dysfunction.

Topics: Biomarkers; Blood Pressure; Carcinoma, Hepatocellular; Cardiac Catheterization; Cardiac Output; Cardiomyopathies; Diastole; Heart; Heart Diseases; Heart Rate; Hemodynamics; Hepatitis B; Hepatitis C; Humans; Hypertension; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Neoplasms; Liver Transplantation; Natriuretic Peptide, Brain; Systole; Vascular Resistance

To determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD).. 22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe).. N-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearman's rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations.. NT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P=0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P<0.001) and the NT-CKD (P<0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P<0.001) and the NT-CKD (P=0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration.. Measurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cat Diseases; Cats; Creatinine; Female; Hypertension; Kidney Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD.. In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification > or =100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment.. FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.

Topics: Aged; C-Reactive Protein; Calcinosis; Chronic Disease; Comorbidity; Coronary Occlusion; Cross-Sectional Studies; Diabetes Mellitus; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Phosphates; Radiography; Single-Blind Method; Ultrasonography; Vitamin D

Oxidative stress followed by abnormal signalling can play a critical role in the development of long-term, high blood pressure-induced cardiac remodelling in heart failure (HF). Since oxidative stress-induced poly(ADP-ribose)polymerase (PARP) activation and cell death have been observed in several experimental models, we investigated the possibility that inhibition of nuclear PARP improves cardiac performance and delays transition from hypertensive cardiopathy to HF in a spontaneously hypertensive rat (SHR) model of HF.. SHRs were divided into two groups: one received no treatment (SHR-C) and the other (SHR-L) received 5 mg/kg/day L-2286 (PARP-inhibitor) orally for 46 weeks. A third group was a normotensive age-matched control group (CFY) and a fourth was a normotensive age-matched group receiving L-2286 treatment 5 mg/kg/day (CFY+L). At the beginning of the study, systolic function was similar in both CFY and SHR groups. In the SHR-C group at the end of the study, eccentric hypertrophy with poor left ventricular (LV) systolic function was observed, while PARP inhibitor treatment preserved systolic LV function. Due to these favourable changes, the survival rate of SHRs was significantly improved (P < 0.01) by the administration of the PARP inhibitor (L-2286). The PARP inhibitor used did not affect the elevated blood pressure of SHR rats, but moderated the level of plasma-BNP (P < 0.01) and favourably influenced all the measured gravimetric parameters (P < 0.05) and the extent of myocardial fibrosis (P < 0.05). The inhibition of PARP increased the phosporylation of Akt-1/GSK-3beta (P < 0.01), ERK 1/2 (P < 0.01), and PKC epsilon (P < 0.01), and decreased the phosphorylation of JNK (P < 0.05), p-38 MAPK (P < 0.01), PKC pan betaII and PKC zeta/lambda (P < 0.01), and PKC alpha/betaII and delta (P < 0.05).. These data demonstrate that chronic inhibition of PARP induces long-term favourable changes in the most important signalling pathways related to oxidative stress. PARP inhibition also prevents remodelling, preserves systolic function, and delays transition of hypertensive cardiopathy to HF in SHRs.

Topics: Administration, Oral; Animals; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Disease Progression; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; JNK Mitogen-Activated Protein Kinases; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Piperidines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Protein Kinase C; Proto-Oncogene Proteins c-akt; Quinazolines; Rats; Rats, Inbred SHR; Signal Transduction; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Hypertension is associated with an increase in vasoactive peptides, but conflicting results are reported concerning their causes of elevation. In this study, cardiac vasodilator hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), and vasoconstrictor hormones (renin, aldosterone, cortisol, metanephrins) were determined in 36 hypertensive subjects (HT) without left ventricular hypertrophy (LVH), 19 healthy subjects without family hypertension (NTFN) and 35 healthy subjects with family hypertension (NTFH). Plasma levels of ANP and BNP were significantly higher (p<0.04) in HT subjects (28.1 +/- 6.1 and 22.7 +/- 6.8 pg/ml) compared to NTFN (13.4 +/- 3.3 and 6.1 +/- 1.5 pg/ml) and NTFH (12.5 +/- 1.4 and 7.2 +/- 1.3 pg/ml) subjects, respectively. No significant differences were observed in ANP and BNP concentrations between NTFN and NTFH. Measurement of vasoconstrictor hormones showed no significant differences between the three groups. Plasma ANP and BNP concentrations were significantly correlated in both HT (r=0.73; P<0.001), NTFN (r=0.71; P<0.002) and NTFH (r=0.53; P<0.003) subjects. ANP values were significantly related to systolic blood pressure (r=0.34; P<0.05) in the HT group while BNP values were not. The echocardiographic findings were not correlated with ANP or BNP in the HT patients. This suggests that natriuretic peptides increase is related to the blood pressure elevation rather than LVH to reduce detrimental high BP effects.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Electrocardiography; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Natriuretic Peptide, Brain; Vasoconstriction; Vasodilation

Aim of the study was to investigate relationship between arterial hypertension (AH), left ventricular myocardial mass (LVMM), and levels of N-terminal pro-B type natriuretic peptide (pro-NT BNP) in a population of women inhabitants of Tallinn aged 56-65 years. Of 163 women aged 50-59 years who had participated in epidemiological study in 2000 in 132 measurement of arterial pressure (AP), electrocardiography, echocardiography, complex laboratory diagnostics including determination of pro-NT BNP were repeated in 2007. Most frequent risk factor was AH which was detected in 56.1% of cases. In women with normal AP normal LVMM was noted in 81.1% of cases, while in women with elevated AP normal LVMM was significantly less frequent (28.4%). Only in 5 of 28 women with elevated pro-NT BNP deviations of systolic-diastolic function were observed. Elevated levels of pro-NT BNP were found with almost equal rates among patients with normal and increased LWMM (in 9.1 and 8.3% of cases, respectively). Thus increase of content of pro-NT BNP is of limited significance for diagnosis of left ventricular hypertrophy in women aged 56-65 years without clinical signs of disease.

Topics: Aged; Disease Progression; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Ventricular Function, Left

Echocardiographically determined inappropriateness of left ventricular mass (LVM) is an independent risk factor for cardiovascular events. Although LV hypertrophy is associated with an increase in the plasma brain natriuretic peptide level and decreased LV diastolic filling, it is unknown whether the inappropriateness of LVM affects them. We studied 77 untreated hypertensive patients (49 men, 28 women, aged 59+/-12 years). The plasma brain natriuretic peptide level was measured, in addition to routine echo Doppler indexes of LV geometry and function. The appropriateness of LVM to cardiac workload was evaluated by the ratio of the observed LVM to the value predicted for individual sex, stroke work and height(2.7) (oLVM/pLVM). Multivariate analysis showed that the plasma brain natriuretic peptide level increased with LVM index but decreased when oLVM/pLVM increased. The ratio of the peak early diastolic flow velocity of mitral flow to the peak early diastolic velocity of mitral annulus (E/E') correlated not only with oLVM/pLVM but also with the LVM index (r=0.30, P<0.05; r=0.37, P<0.05, respectively). However, when a multiple stepwise regression analysis was carried out, only LVM index was determined to be a significant correlate of the E/E' ratio, indicating that the inappropriateness of LVM does not affect the E/E' ratio in hypertensive patients. Brain natriuretic peptide levels are influenced not only by the extent of LV hypertrophy but also by the inappropriateness of hypertrophy in untreated hypertensive patients. Diastolic filling is mostly affected by the extent of LV hypertrophy and not by the appropriateness of hypertrophy.

Topics: Aged; Algorithms; Blood Pressure; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; Stroke Volume; Ultrasonography

Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for volume-overloaded heart failure or sham surgery. All rats with a fistula received either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by gavage. Two weeks later, the LS diet significantly increased the plasma aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1% with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial fibrosis in fistula-created rats was more prominent with the LS diet than with the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on the LS diet expressed significantly increased oxidative stress and transforming growth factor-beta compared with those on the NS diets (P<0.05). These increases in the fistula-created rats on the LS diet were significantly suppressed by the non-hypotensive dose of spironolactone (P<0.05). These results suggest that increased plasma aldosterone level with strict salt restriction activated the mineralocorticoid receptor signaling in volume-overloaded condition, resulting in increased myocardial fibrosis.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Body Weight; Cell Size; Contraindications; Diet, Sodium-Restricted; Endomyocardial Fibrosis; Heart; Heart Failure; Hemodynamics; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; Signal Transduction; Spironolactone; Transforming Growth Factor beta; Tyrosine; Ventricular Remodeling

Hypertension may affect the diagnostic performance of B-type natriuretic peptide (BNP). The objective of the present study was to assess the impact of a history of hypertension or blood pressure elevation on admission on the diagnostic performance of BNP in the diagnosis of heart failure (HF) in patients with acute dyspnea. BNP levels were measured using a rapid point-of-care device in 1,586 patients with acute dyspnea. In patients with HF, BNP levels did not differ between those with and without histories of hypertension. Conversely, in patients without HF, a history of hypertension was associated with higher median BNP levels (38 pg/ml [interquartile range 13 to 119] vs 21 pg/ml [interquartile range 7 to 64], p <0.001). The areas under the receiver-operating characteristic curves were 0.88 and 0.93 for those with and without histories of hypertension, respectively (p <0.001). Blood pressure elevation on admission did not affect the diagnostic accuracy of BNP (areas under the curve 0.90 in the 2 groups). In conclusion, although a history of hypertension is associated with higher BNP levels in patients with acute dyspnea without HF, the impact on the overall diagnostic performance of BNP is modest. Accordingly, BNP performs well as an indicator of HF in patients presenting in emergency departments regardless of a history of hypertension or elevated blood pressure on admission.

Topics: Acute Disease; Aged; Biomarkers; Blood Pressure Determination; Cohort Studies; Confidence Intervals; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Probability; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

B-type natriuretic peptide (BNP) has prognostic implications in patients with acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients with evidence of subclinical disease remains unclear. The population of this study included 2,458 asymptomatic adults (47% women) with an average Framingham risk score of 8.8 +/- 7% who underwent computed tomographic evaluation of coronary artery calcium (CAC). BNP levels were measured using the Triage CardioProfilER panel method. Cox proportional-hazards models were used to estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48 diagnoses of incident symptomatic coronary disease). Relative risk was calculated. The median follow-up time was 3.9 years (25th and 75th percentiles 2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP values of 40 to 99.9 and > or =100 pg/ml (p <0.0001) compared to BNP <40 pg/ml. Similarly, CAC score was also highly predictive of CV events, with elevated hazard ratios of 2.8- to 48.7-fold for scores of 11 to 100 to > or =1,000 (p <0.0001) compared to no CAC. In a stepwise model, BNP was the second greatest estimator of CV outcomes (p = 0.016) after CAC (p <0.0001), even in models that included blood pressure and age. Hypertension, age > or =65 years, and CAC contained 28.4%, 40.7%, and 56.8%, respectively, of BNP risk. The combination of BNP > or =100 pg/ml and CAC score > or =400 identified 52.4% and 35.7% of CV events in patients with hypertension and in elderly patients beyond the Framingham risk score. In conclusion, BNP and CAC are independently predictive of CV events.

Topics: Age Factors; Aged; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Stroke; Tomography, X-Ray Computed

The aim was to evaluate the usefulness of urinary N-terminal fragment of B-type natriuretic peptide (NT-proBNP) measurement for predicting the presence of left ventricular hypertrophy (LVH) in 160 asymptomatic patients with essential hypertension. The urinary NT-proBNP/creatinine ratio was higher in patients with LVH than in either those without LVH (P< .0001) or control subjects (P< .0001). Multivariate linear regression analysis identified age (P=.034), left ventricular mass index (P=.026) and serum NT-proBNP level (P=.001) as predictors of the urinary peptide level. The area under the curve for the NT-proBNP/creatinine ratio was 0.71+/-0.04 (P< .0001) for identifying LVH. Logistic regression analysis showed that the NT-proBNP: creatinine ratio was a predictor of LVH (odds ratio=4.074; P=.009). In conclusion, the urinary NT-proBNP concentration is a new marker that could be useful for identifying LVH in subjects with essential hypertension.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are circulating hormones secreted predominantly in patients with hypertension or congestive heart failure. To obtain background data on plasma ANP and BNP levels in rats, we investigated the circadian rhythms and effects of anesthesia on these peptides. To determine the circadian rhythms, plasma samples from thirty rats were collected by non-anesthesia (decapitation) at six time points every fourth hour. To determine the effects of anesthesia, plasma samples from thirty-two rats were collected under diethyl ether, pentobarbital or urethane anesthesia. The plasma ANP and BNP levels were determined using a radioimmunoassay. The plasma ANP levels were high from the evening to early morning, while the plasma BNP levels were relatively low at 2:30 AM. The difference in the BNP levels was statistically significant. The plasma BNP levels were relatively high when the rats were anesthetized using urethane. These results suggest that blood collection should be performed between 10:30 AM to 2:30 PM to determine plasma ANP and BNP. The use of pentobarbital is also recommended for toxicological studies in rats.

Topics: Anesthesia; Animals; Atrial Natriuretic Factor; Biomarkers; Circadian Rhythm; Ether; Heart Failure; Hypertension; Male; Natriuretic Peptide, Brain; Pentobarbital; Rats; Rats, Sprague-Dawley; Urethane

The purpose of this study was to define a correlation between N-terminal proBNP level and extent of cardiac abnormalities. A total of 40 patients with hypertension were included in the study (60.5+/-7.6 years of age; 18 men, 22 women). It was found that patients with hypertension had increased plasma N-terminal proBNP level, that it increased with age and tended to be higher in patients with concentric hypertrophy compared with those with normal geometry and eccentric hypertrophy; however, the differences were not significant. N-terminal proBNP concentration depended on ventricular septal thickness and left ventricular wall thickness. Analysis of association between N-proBNP level and parameters of myocardial diastolic function showed that increased plasma peptide levels correlated with degree of diastolic dysfunction in patients with altered left ventricular relaxation.

Topics: Aged; Female; Heart; Heart Function Tests; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Remodeling

Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage.. We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using

Topics: Aldosterone; Antihypertensive Agents; Atrial Natriuretic Factor; Case-Control Studies; Drug Resistance; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Potassium; Regression Analysis; Renin; Sex Factors; Sodium

To assess the effect of angiotensin II type 1 (AT(1)) receptor antagonist losartan on myocardium connexin43 (Cx43) gap junction (GJ) expression in spontaneously hypertensive rats (SHRs) and investigate possible mechanisms.. Sixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto (WKY) rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30 mg/(kg x d) by oral gavage once daily for 8 weeks (SHR-L) or vehicle (0.9% saline) to act as controls (SHR-V); WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 (NF-kappaB p65) proteins in all three groups were observed and further investigations on the effect of angiotensin II type 1 receptor antagonist losartan (30 mg/(kg x d), 8 weeks) on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-kappaB p65 protein in nuclear extracts was determined by Western blot.. Left ventricular (LV) hypertrophy was prominent in SHRs, Cx43 and NF-kappaB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-kappaB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment.. Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin II type 1 receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-kappaB pathway.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Blood Pressure; Blotting, Western; Connexin 43; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Transcription Factor RelA

Left ventricular (LV) hypertrophy and dysfunction due to hypertension have been established as risk markers for stroke in hypertensive patients. The purpose of this study was to examine the differences in LV hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction. The study enrolled 23 hypertensive patients with cerebral infarction, 25 hypertensive patients with cerebral hemorrhage, and 24 normotensive controls (controls). Standard echocardiography was performed; LV mass index was measured to evaluate LV hypertrophy, and conventional diastolic transmitral flow velocities were measured to assess LV diastolic function, which was also evaluated by measuring mitral annular velocities using tissue Doppler echocardiography. The Tei index, which reflects both the diastolic and systolic function of LV, was also calculated. The LV mass index and Tei index were significantly higher in cerebral hemorrhage (116 +/- 38 g/m(2) and 0.57 +/- 0.13) than those in controls (92 +/- 20 g/m(2) and 0.46 +/- 0.10) (p < 0.05). In contrast, the LV mass index and Tei index in cerebral infarction (100 +/- 27 g/m(2) and 0.46 +/- 0.12) were not different from those in controls. Thus, the Tei index was significantly worse in the patients with cerebral hemorrhage than in those with cerebral infarction (p < 0.05). On the other hand, the parameters, which reflect diastolic function, showed no significant differences between cerebral hemorrhage and cerebral infarction. These results indicate that LV hypertrophy and dysfunction due to hypertension are more apparent in patients with cerebral hemorrhage than in those with cerebral infarction.

Topics: Aged; Blood Pressure; Case-Control Studies; Cerebral Hemorrhage; Cerebral Infarction; Diastole; Echocardiography, Doppler, Pulsed; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

To evaluate BNP in assessing LV functions in asymptomatic type 2 diabetic patients.. BNP was measured in 91 consecutive patients with type 2 diabetes mellitus. According to Doppler echocardiography, patients were first separated into three categories: normal LV function, or isolated diastolic or systolic LV dysfunction. As some patients with diastolic dysfunction were treated for hypertension, the population was divided into four groups: groups 1, 2 and 3 all had no antihypertensive treatment, and had normal LV function, and isolated diastolic and systolic LV dysfunction, respectively; and group 4 were being treated with antihypertensive drugs and had diastolic LV dysfunction.. In group 1, BNP levels (13+/-2 ng/L) were lower than in group 2 (87+/-20 ng/L, P<0.0001) or group 3 (213+/-32 ng/L, P<0.0001), but were similar to those of group 4 (32+/-6 ng/L, P=0.14). ROC analysis revealed a rule-out value of 23 ng/L for group 1 versus group 2, and of 239 ng/L for group 2 versus group 3. In groups 1, 2 and 3 taken together, BNP levels were correlated with urinary albumin excretion rate (r=0.80, P<0.0001) and pulse pressure (r=0.65, P<0.0001). In group 4, patients receiving ACE inhibitors had lower BNP levels than those receiving ss-blockers.. BNP can be used to pre-screen asymptomatic type 2 diabetic patients with LV dysfunction, and may reveal vascular remodelling in type 2 diabetes mellitus.

Topics: Aged; Antihypertensive Agents; Biomarkers; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Regression Analysis; Ventricular Dysfunction, Left

Cardiac hypertrophy is common in diabetes and an independent risk factor for cardiac morbidity and mortality. We investigated the effects of pioglitazone on cardiac hypertrophy and hypertrophic signaling in Dahl salt-sensitive hypertensive rats.. Dahl salt-sensitive rats were fed a high-salt diet from 7 weeks of age and treated with pioglitazone (2.5 mg/kg per day) or vehicle from 7 to 11 weeks.. The vehicle-treated rats developed left ventricular hypertrophy and fibrosis as well as left ventricular diastolic dysfunction. The serum level of adiponectin and the phosphorylation of AMP-activated protein kinase in the myocardium did not differ between the vehicle-treated rats and control rats maintained on a normal diet. The phosphorylation of Akt, mammalian target of rapamycin, and p70S6 kinase as well as the total protein content were increased in the heart of vehicle-treated rats compared with control rats, and these changes were blocked by treatment with pioglitazone. Pioglitazone treatment also ameliorated left ventricular hypertrophy and fibrosis, improved diastolic function, and increased both the serum adiponectin concentration and the level of AMP-activated protein kinase phosphorylation in the heart.. Long-term administration of pioglitazone attenuated left ventricular hypertrophy and fibrosis as well as inhibited phosphorylation of mammalian target of rapamycin and p70S6 kinase in the heart of hypertensive rats. The beneficial cardiac effects of pioglitazone are likely attributable, at least partly, both to the activation of AMP-activated protein kinase signaling through stimulation of adiponectin secretion and to the inhibition of Akt signaling.

Topics: Adiponectin; AMP-Activated Protein Kinases; Animals; Atrial Natriuretic Factor; Collagen; Echocardiography; Fibrosis; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Male; Multienzyme Complexes; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phosphorylation; Pioglitazone; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Inbred Dahl; Ribosomal Protein S6 Kinases, 70-kDa; RNA, Messenger; Signal Transduction; Thiazolidinediones; Transcription Factors

Topics: Biomarkers; Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Ultrasonography

No agreement has been reached regarding the best strategy to detect left ventricular hypertrophy (LVH). This study examined the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of LVH in hypertensive patients and the potential factors that may influence its diagnostic performance.. The global accuracy of NT-proBNP in diagnosing LVH was assessed using a receiver-operating characteristic (ROC) curve. The influence of patients' characteristics on test accuracy was studied with a ROC regression based on a probit model. Ninety-three subjects were included. All had NT-proBNP measured and underwent electrocardiography and echocardiography, with calculation of the left ventricular mass index (LVMI).. The diagnostic performance of NT-proBNP in LVH varied slightly depending on the indexation mode of LVMI. In cases of body surface area indexation, the area under the ROC curve of 81.6% suggested a good performance. The accuracy of the marker was significantly higher in women than in men (p<0.0001). There were no significant effects of age, treatment, body mass index, left ventricular mass index, 24-h systolic blood pressure, or creatinine clearance on the test performance. Slight differences were observed when an indexation to height(2.7) instead of body surface area was used.. The present results may lead to a new strategy for risk stratification in hypertension: in women, NT-proBNP alone or preferably in combination with electrocardiography seems sufficient to confirm or exclude diagnosis of LVH. In men, echocardiography would only be needed in cases of negative electrocardiography and NT-proBNP test.

Topics: Adult; Aged; Biomarkers; Body Height; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Sex Factors; Young Adult

Corin is a cardiac serine protease that acts as the pro-atrial natriuretic peptide (ANP) convertase. Recently, 2 single-nucleotide polymorphisms (SNPs) (T555I and Q568P) in the human corin gene have been identified in genetic epidemiological studies. The minor I555/P568 allele, which is more common in African Americans, is associated with hypertension and cardiac hypertrophy. In this study, we examined the effect of T555I and Q568P amino acid substitutions on corin function. We found that corin frizzled-like domain 2, where T555I/Q568P substitutions occur, was required for efficient pro-ANP processing in functional assays. Mutant corin lacking this domain had 30+/-5% (P<0.01) activity compared to that of wild type. Similarly, corin variant T555I/Q568P had a reduced (38+/-7%, P<0.01) pro-ANP processing activity compared to that of wild type. The variant also exhibited a low activity (44+/-15%, P<0.05) in processing pro-brain natriuretic peptide (BNP). We next examined the biochemical basis for the loss of activity in T555I/Q568P variant and found that the zymogen activation of the corin variant was impaired significantly, as indicated by the absence of the activated protease domain fragment. This finding was confirmed in human embryonic kidney (HEK)293 cells and murine HL-1 cardiomyocytes. Thus, our results show that the corin gene SNPs associated with hypertension and cardiac hypertrophy impair corin zymogen activation and natriuretic peptide processing activity. Our data suggest that corin deficiency may be an important mechanism in hypertensive and heart diseases.

Topics: Atrial Natriuretic Factor; Cardiomegaly; Cell Line; Enzyme Precursors; Genetic Variation; Humans; Hypertension; Kidney; Membrane Proteins; Mutagenesis; Natriuretic Peptide, Brain; Natriuretic Peptides; Polymorphism, Single Nucleotide; Protein Structure, Tertiary; Serine Endopeptidases; Substrate Specificity; Transfection

Doppler echocardiography (DE), chest radiography (CXR), serum B-type natriuretic peptide (BNP) measurement and physical examination are all commonly employed to estimate left ventricular diastolic pressure (LVDP) in clinical care. There are no published studies directly comparing the diagnostic accuracy of these tests.. DE, BNP, CXR, and physical examination were performed on 56 consecutive patients immediately following clinically indicated cardiac catheterization with measurement of LVDP. LVDP measured preceding atrial contraction at end-expiration was elevated (>16 mmHg) in 19 subjects. Diagnostic accuracies were 79%, 70%, 61% for DE, BNP, and CXR, respectively. None of the study subjects had evidence of raised LVDP by chest auscultation.. The diagnostic accuracy of DE compares favorably to other noninvasive markers for prediction of invasively determined LVDP.

Topics: Echocardiography, Doppler; Female; Heart Auscultation; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Radiography, Thoracic; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left

The presence of left ventricular hypertrophy (LVH) is associated with an increase in cardiovascular morbidity and mortality in hypertensive patients. We investigated the diagnostic value of the N-terminal probrain natriuretic peptide (NT-proBNP) level for detecting LVH in hypertensive patients with a conserved left ventricular ejection fraction. The study involved 27 consecutive patients. Cardiac magnetic resonance imaging was performed to determine left ventricular mass and the plasma NT-proBNP level was measured. A significant correlation was found between the NT-proBNP level and left ventricular mass (r=0.598; P=.001). Use of a cut-off point of 35 pg/mL enabled the presence of LVH to be identified with a sensitivity of 100% (95% confidence interval [CI], 69%-100%) and a specificity of 70.6% (95% CI, 44.1%-89.6%). The area under the receiver operating characteristic (ROC) curve was 0.867 (95% CI, 0.73-1; P< .05). The plasma NT-proBNP level may be useful for identifying patients with LVH.

Topics: Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

We previously reported the feasibility of an acute, orally delivered, newly developed, conjugated form of human B-type natriuretic peptide (hBNP) in normal animals. The objective of the present study was to extend our findings and to define the chronic actions of an advanced oral conjugated hBNP (hBNP-054) administered for 6 days on sodium excretion and blood pressure. We also sought to establish the ability of this new conjugate to acutely activate cGMP and to reduce blood pressure in an experimental model of angiotensin II (ANG II) -mediated hypertension.. First, we developed additional novel conjugated forms of oral hBNP that were superior to our previously reported hBNP-021 in reducing blood pressure in 6 normal dogs. We then tested the new conjugate, hBNP-054, chronically in 2 normal dogs to assess its biological actions as a blood pressure-lowering agent and as a natriuretic factor. Second, we investigated the effects of acute oral hBNP-054 or vehicle in 6 dogs that received continuous infusion of ANG II to induce hypertension. After baseline determination of mean blood pressure (MAP) and blood collection for plasma hBNP and cGMP, all dogs received continuous ANG II infusion (20 ng . kg(-1) . min(-1), 1 mL/min) for 4 hours. After 30 minutes of ANG II, dogs received oral hBNP-054 (400 microg/kg) or vehicle in a random crossover fashion with a 1-week interval between dosing. Blood sampling and MAP measurements were repeated 30 minutes after ANG II administration and 10, 30, 60, 120, 180, and 240 minutes after oral administration of hBNP-054 or vehicle. In the chronic study in normal dogs, oral hBNP-054 effectively reduced MAP for 6 days and induced a significant increase in 24-hour sodium excretion. hBNP was not present in the plasma at baseline in any dogs, and it was not detected at any time in the vehicle group. However, hBNP was detected throughout the duration of the study after oral hBNP-054, with a peak concentration at 30 minutes of 1060+/-818 pg/mL. In the acute study, after ANG II administration, plasma cGMP was not activated after vehicle, whereas it was significantly increased after oral hBNP-054 (P=0.01 between the 2 groups). Importantly, MAP was significantly increased after ANG II throughout the acute study protocol. However, although no changes occurred in MAP after vehicle administration, oral hBNP-054 reduced MAP for >2 hours (from 138+/-1 mm Hg after ANG II to 124+/-2 mm Hg at 30 minutes, 124+/-2 mm Hg at 1 hour, and 130+/-5 mm Hg at 2 hours after oral hBNP-054; P<0.001).. This study reports for the first time that a novel conjugated oral hBNP possesses blood pressure-lowering and natriuretic actions over a 6-day period in normal dogs. Furthermore, hBNP-054 activates cGMP and reduces MAP in a model of acute hypertension. These findings advance the concept that orally administered chronic BNP is a potential therapeutic strategy for cardiovascular diseases such as hypertension.

Topics: Administration, Oral; Amino Acid Sequence; Angiotensin II; Animals; Dogs; Drug Administration Schedule; Hypertension; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Random Allocation

Increased B-type natriuretic peptide (BNP) expression precedes the development of hypertension in spontaneously hypertensive rats. We therefore tested the hypothesis that elevated plasma BNP levels predict the onset of hypertension in normotensive subjects. Japanese normotensive participants who were at our hospital for a yearly physical check-up (mean age 52.7 years, 35.9% women, n=5,026) were enrolled in the study. Blood pressure and BNP were measured at baseline and subjects were followed up for 5 years (median 1,114 d), with the endpoint being the development of hypertension. We evaluated the relationship between plasma BNP levels at baseline and the incidence of hypertension during the follow-up period. Hypertension was defined as systolic or diastolic blood pressure > or =140 or > or =90 mmHg, respectively, or the use of antihypertensive medications. During the follow-up period, hypertension developed in 23.4% (77.0 per 1,000 person-years) and 14.9% (51.0 per 1,000 person-years) of male and female subjects, respectively. Cox proportional hazard regression analysis demonstrated that after adjustment for known risk factors, the risk of hypertension was increased from the first to fourth quartiles of baseline BNP levels. However, after additional adjustment for baseline blood pressure, BNP did not predict the new onset of hypertension. Baseline BNP levels are closely associated with the risk of hypertension in individuals with normal blood pressure, but the prediction of hypertension with BNP is largely dependent on baseline blood pressure. Measurements of BNP may serve as a complementary method for the prediction or confirmation of hypertension.

Topics: Adult; Asian People; Blood Pressure; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Japan; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors

This study was designed to investigate: 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; and the 3) expression of ST2, membrane-anchored ST2L, and its ligand, interleukin (IL)-33, in myocardium, endothelium, and leukocytes from patients with left ventricular (LV) pressure overload and congestive cardiomyopathy.. Serum levels of ST2 are elevated in heart failure. The relationship of ST2 to hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown.. Serum ST2 (pg/ml; median [25th, 75th percentile]) was measured in patients with LV hypertrophy (aortic stenosis) (n = 45), congestive cardiomyopathy (n = 53), and controls (n = 23). ST2 was correlated to N-terminal pro-brain natriuretic peptide, C-reactive protein, and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. The levels of ST2, ST2L, and IL-33 were measured (reverse transcriptase-polymerase chain reaction) in myocardial biopsies and leukocytes. The ST2 protein production was evaluated in human endothelial cells. The IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium.. The ST2 protein was elevated in aortic stenosis (103 [65, 165] pg/ml, p < 0.05) and congestive cardiomyopathy (194 [69, 551] pg/ml, p < 0.01) versus controls (49 [4, 89] pg/ml) and correlated with B-type natriuretic peptide (r = 0.5, p < 0.05), C-reactive protein (r = 0.6, p < 0.01), and LV end-diastolic pressure (r = 0.38, p < 0.03). The LV ST2 messenger ribonucleic acid was similar in aortic stenosis and congestive cardiomyopathy versus control (p = NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. The IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r = 0.97, p < 0.001).. In human hypertrophy and failure, serum ST2 correlates with the diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.

Topics: Aged; C-Reactive Protein; Case-Control Studies; Diastole; Endothelium, Vascular; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Leukocytes; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Prognosis; Receptors, Cell Surface

The present study attempted to determine the accuracy of B-type natriuretic peptide (BNP) compared with left atrial enlargement at echocardiography in the emergency diagnosis of new-onset heart failure with preserved systolic function (HFPSF) related to longstanding hypertension. The study comprised 57 patients in sinus rhythm hospitalized for acute dyspnea, 30 with hypertensive HFPSF and 27 with noncardiac cause. By stepwise logistic regression analysis, BNP provided independent and incremental diagnostic information over the score of Boston criteria. There was a trend toward superiority of this biomarker compared to the left atrial area index for the diagnosis of HFPSF. A BNP concentration >142 pg/ml was 93% sensitive and 85% specific for the diagnosis of HFPSF in this clinical setting (area under the ROC curve of 0.91 [0.8-0.97], p<0.001).

Topics: Aged; Aged, 80 and over; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Humans; Hypertension; Logistic Models; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Regression Analysis; ROC Curve; Sensitivity and Specificity; Systole; Ventricular Function, Left

The utility of N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) and Brain Natriuretic Peptide (BNP) for detecting left ventricular (LV) diastolic dysfunction in hypertensive patients without heart failure symptoms is unclear. In this study, we investigated the relation between NT-proBNP plasma levels and LV diastolic dysfunction in hypertensive patients without systolic dysfunction.. We studied 40 ambulatory patients (26 women, mean age 52 +/- 5) with controlled hypertension. LV diastolic function was assessed with conventional Doppler, by means of mitral inflow and with tissue Doppler echocardiography by means of mitral annulus. The ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic E' wave velocities (E/E'), was used to detect LV filling pressures. Patients were divided in three groups according to E/E' ratios < 10 (group I), E/E' ratios ''between'' 10 and 15 (group II) and E/E' ratios > 15 (group III). Plasma concentrations of NT-proBNP were measured by electro chemiluminescence's immunoassay.. The NT-proBNP blood levels were positively correlated significantly with E/E' ratio (r = 0.80, P < 0.0001). Patients with elevated LV end diastolic pressure (LVEDP), defined as E/E' > 15 (n = 8) had highest NT-proBNP (203 +/- 75 pg/ml) levels. E/E' 10 to 15 group (n = 16) had a mean NT-proBNP level of 71 +/- 26 pg/ml, and those with E/E' < 10 (n = 16) had 39 +/- 20 pg/ml. A NT-proBNP value of 119 pg/ml had a sensitivity of 87%, a specificity of 100% for predicting E/E' > 15.. The assessment of the blood concentration of NT-proBNP is of potential value for identification of those patients with hypertension to detect early cardiovascular changes, especially LV diastolic dysfunction.

Topics: Diastole; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) level has been used as a marker of left ventricular (LV) systolic dysfunction (LVSD), even though some patients with atherosclerosis have a high BNP level irrespective of LV function. In this study, we investigate whether augmentation index (AI), which is an index of wave reflection, is involved in increasing BNP level in hypertensive patients without LVSD. Sixty treated hypertensive patients were enrolled in this study. Radial AI (r-AI) was measured in all patients. The patients were classified into tertiles on the basis of r-AI to identify the characteristics of the patients with a high r-AI. BNP level was significantly higher in the patients classified into the highest tertile of r-AI. In echocardiography, e', which is index of left ventricular (LV) diastolic function, decreased and LV mass index (LVMI) increased gradually with r-AI, whereas there was no difference in LV ejection fraction (LVEF). r-AI significantly correlated with LVMI (r=0.35, p<0.01) and e' (r=-0.30, p<0.05). In univariate analysis, age, heart rate, r-AI, LVEF, e' and LVMI were significantly correlated with BNP level, whereas multivariate analysis demonstrated that only r-AI and LVEF correlated with BNP level. In conclusion, an increase in r-AI was significantly associated with an increase in BNP level in hypertensive patients without LVSD. LV hypertrophy and diastolic dysfunction associated with increase in r-AI may be involved in increase in BNP level.

Topics: Aged; Diastole; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Ventricular Function, Left

The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Northern; Blotting, Western; Cardiomegaly; Collagen; Hypertension; Male; Mice; Mice, Transgenic; Microscopy, Confocal; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 2; RNA, Messenger; Survival Analysis; Ventricular Function, Left

The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night.. We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FE(Na)), free water clearance (C(H2O)), urinary excretion of aquaporin 2 (u-AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation.. OSA patients had a higher FE(Na) (0.6 (0.4-1.0) versus 0.4 (0.3-0.6) %; p = 0.017), SBP (129 (114-145) versus 114 (106-122) mmHg; p = 0.001) and DBP (81 (72-87) versus 71 (65-74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FE(Na) correlated significantly with the change in nocturnal DBP (r (2) = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8-1.4) versus 0.8 (0.6-1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, C(H2O) and u-AQP2 were the same in OSA and controls.. We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.

Topics: Adult; Age Factors; Aldosterone; Aquaporin 2; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Oxygen; Potassium; Sex Factors; Sleep Apnea, Obstructive; Sodium; Vasopressins; Water

to evaluate whether pro BNP can be used for detection of diastolic dysfunction.. thirty nine hypertensive patients with normal systolic function, consecutively referred for echocardiography examination between October and December 2004 were recruited in the study. Diastolic dysfunction was diagnosed when echocardiographic mitral flow pattern demonstrated impaired relaxation, pseudonormalization or restrictive like patterns. NT-pro BNP levels were assessed using electro chemiluminescence Immunoassay (ECLIA) method. Unpaired t test was used to analyze the results.. twelve out of thirty nine subjects had normal diastolic function. All base line characteristics, except for uric acid, were equally distributed between normal and abnormal diastolic function group. NT-pro BNP levels were nearly significantly higher in the diastolic dysfunction group (P=0.053).. NT-pro BNP levels trends to be higher in hypertensive subjects with diastolic dysfunction.

Topics: Diastole; Echocardiography, Doppler, Pulsed; Female; Humans; Hypertension; Immunoassay; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

The objective of this study was to compare heart rate variability (HRV) in patients with essential hypertension, in patients with white-coat hypertension and in normotensive control individuals, and to investigate a possible relation between HRV and vasoactive hormones.. Patients with essential hypertension (n=19, 61 years, median and interquartile range: 40-66 years), patients with white-coat hypertension (n=8, 52 years, median and interquartile range: 41-64 years) and normotensive participants (n=13, 50 years, median and interquartile range: 39-57 years) participated in the study. HRV was measured at rest in the supine position, during standing and during controlled forced breathing (respiration frequency >20/min). Power spectral density was calculated using Fourier transformation.. Controlled breathing caused a decrease in low frequency (LF) variation and LF/high frequency variation (LF/HF) in all blood pressure groups. The decrease in LF was smaller in the hypertensive group (-60 ms2) than in the normotensive group (-139 ms2) (P=0.03; hypertensive group vs. normotensive group). The decrease in LF/HF induced by controlled breathing was -0.9 ms in the hypertensive group, -2.0 ms2 in the white-coat hypertensive group and -2.8 ms2 in the normotensive group, (P=0.037; hypertensive group vs. normotensive group). We found a positive correlation between baseline plasma renin concentration and LF (r=0.330, P=0.037) and LF/HF (r=0.378, P=0.016) at rest.. The observed differences in HRV might reflect the impaired responsiveness to autonomic challenge in hypertensive patients. We did not find the HRV spectrum in white-coat hypertension different from the HRV spectrum in hypertension or normotension.

Topics: Adult; Aged; Aldosterone; Angiotensins; Arginine Vasopressin; Autonomic Nervous System; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Breathing Exercises; Case-Control Studies; Endothelins; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Physician-Patient Relations; Renin; Renin-Angiotensin System

Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks.. The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL x min(-1) x 1.73 m(-2) and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein-creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (P(interaction)=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression.. These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

Topics: Adolescent; Adult; Aged; Black or African American; Black People; Cardiovascular Diseases; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Factors

Topics: Atrial Fibrillation; Biomarkers; Blood Pressure; Carotid Artery, Common; Diastole; Elasticity; Femoral Artery; Heart Atria; Heart Ventricles; Humans; Hypertension; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulsatile Flow; Research Design; Risk Factors; Stroke; Ultrasonography; Ventricular Remodeling

Arterial stiffness is a strong predictor of cardiovascular events and particularly of stroke. A likely explanation is the development of atherosclerotic lesions at the carotid level, favored by increased local stiffness. Another possibility involves cardiac consequences of aortic stiffness and particularly left atrial dilatation with its subsequent risk of atrial fibrillation (AF) and cerebral embolism.. The present study investigated the link between arterial stiffness, pulse pressure and left atrial size, a determinant of AF risk.. Arterial stiffness was determined from pulse wave velocity (PWV) and pulse pressure (PP). Left atrial size was also measured. Several potential confounders were taken into account including indices of ventricular remodeling and diastolic function (estimated by NT-Pro brain natriuretic peptide (NT-proBNP) levels).. Three-hundred and ten hypertensive patients, aged 53 +/- 13 years, were included. Mean 24-h blood pressure (BP) was 154 +/- 20 over 93 +/- 13 mmHg. Significant relationships were found between left atrial diameter (LAD) and PWV (r=0.27, P<0.001) and between LAD and 24-h PP (r=0.32, P<0.001). LAD was also correlated significantly, although not always tightly, with left ventricular dimensions, geometry and NT-proBNP. In two different multivariate models, LAD remained significantly correlated with PWV or with 24-h PP, independently of classical determinants like age, gender, body mass index, ventricular remodeling (i.e. dimensions and geometry) and filling pressure.. These results led us to propose AF as a new possible pathophysiological link between arterial stiffness and stroke. These results also emphasize the cardiac consequences of arterial stiffness which can fuel a new approach to AF prevention.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Blood Pressure; Carotid Artery, Common; Diastole; Elasticity; Female; Femoral Artery; Heart Atria; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulsatile Flow; Risk Factors; Stroke; Ultrasonography; Ventricular Remodeling

Recently, it was reported that high pulse rate (PR), which was measured using by self-measured blood pressure (BP) monitoring at home, was associated with cardiovascular risk. However, the predictor of high PR at home in treated hypertensives is unknown. In this study, we studied the predictor of high PR and evaluated pulse rate variability (PRV).. In the JMS-1 study, 611 hypertensive outpatients were recruited. Self-measured BP monitoring was conducted consecutively twice in the morning and evening for three days. PR analysis was conducted using the average of these two measurements for three days (six readings in total). We defined home PR as the mean of these six readings. Home PRV was defined as the standard deviation of these six readings.. Multivariate linear regression analysis demonstrated that current smoking (beta = 0.12, p = 0.002), diabetes (beta = 0.16, p < 0.001), lack of angiotensin-converting enzyme (ACE) inhibitor use (beta = 0.10, p = 0.008), decreased brain-type natriuretic peptide (BNP; beta = 0.17, p < 0.001), and elevated home diastolic blood pressure (beta = 0.14, p = 0.009) were determinants of high PR. Determinants of decreased home PRV were female gender (beta = 0.10, p < 0.03) and increased hemoglobin A1c (HbA1c; beta = 0.15, p < 0.001). When we divided the patients into four groups according to home PR and its variability, hypertensives whose home PR was high and variability was low were found to have high HbA1c (ANOVA, p > 0.05).. Smoking habit, diabetes, lack of ACE inhibitor use, and low BNP value were determinants of home PR, and female gender and higher HbA1c were significantly associated with its low variability. Home PR and its variability may be useful for detecting high-risk hypertensive patients, particularly with autonomic neuropathy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure Determination; Circadian Rhythm; Diabetes Complications; Female; Glycated Hemoglobin; Heart Rate; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Self Care; Sex Factors; Smoking

Recent studies suggest that B-type natriuretic peptide (BNP) is an important predictor of cardiac events in hypertensive patients.. The relationship between the plasma BNP level and various clinical parameters was examined in 154 untreated hypertensive patients without heart failure or atrial fibrillation (mean age: 58.0+/-10.7; mean blood pressure: 164.5+/-15.2/99.1+/-9.7 mmHg; mean BNP: 32.7+/-36.7 pg/ml). First, the patients were divided into 2 groups based on BNP: normal (<18.5 pg/ml, mean 9.7+/-5.7, n=69); or elevated (>18.5 pg/ml, mean 51.4+/-40.4, n=85). The elevated BNP group had a significantly greater electrocardiographic voltage index (SV1+RV5; 3.7+/-1.2 vs 3.2+/-0.8 mV, p=0.0029), cardiothoracic ratio/chest radiography (CTR; 49.1 vs 46.9%, p=0.0037), left ventricular mass index (LVMI; 122.2+/-31.7 vs 103.1+/-26.4 g/m2, p=0.0005) and deceleration time (DT; 241+/-39 vs 208+/-30 ms, p=0.0001), as well as a smaller E-wave to A-wave (E/A ratio) (0.80+/-0.22 vs 0.96+/-0.28, p=0.0003), compared with the normal BNP group. There were no significant differences in casual blood pressure, body mass index, serum creatinine and ejection fraction between the 2 groups. Next, the patients were divided into 3 groups based on BNP: normal (<18.5, n=69), moderate (18.5 to 40, mean 27.0+/-5.7, n=43) and high (40<, mean 76.3+/-45.3, n=42). In the high BNP group, most clinical parameters indicated the most severe organ damage compared with other groups, including SV1+RV5, DT and LVMI. In all patients, logarithmic BNP was positively correlated with the age, pulse pressure, SV1+RV5, CTR, ventricular wall thickness, DT, LVMI and negatively correlated with hemoglobin, renin and E/A ratio. Using multiple regression analysis, renin and DT were significantly associated with BNP. No gender differences in the relationship between BNP and clinical parameters were found.. Results suggest that BNP is a useful indicator for the initial assessment of the severity of essential hypertension, detecting both cardiac hypertrophy and diastolic dysfunction, and may also be valuable for risk stratification.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Cardiomegaly; Diastole; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prevalence; Regression Analysis; Severity of Illness Index

Multiple studies have focused on the influence of obesity on natriuretic peptide levels. However, the effect of obesity on amino-terminal propeptide of B-type natriuretic peptide (NT-proBNP) levels in hypertensive (HT) patients remains uncertain.. We studied 252 asymptomatic patients (60 +/- 13 years, 136 men) with essential HT. A routine physical examination, anthropometry, laboratory analyses, echo-Doppler study, and NT-proBNP level determination were performed.. NT-proBNP levels were similar in both obese and nonobese HT (median 56 (25-130) pg/ml vs. median 51 (26-129) pg/ml, P = 0.488). No significant differences were found in obese or nonobese patients with left ventricular hypertrophy (LVH) (median 135 (73-425) pg/ml vs. median 151 (64-274) pg/ml, P = 0.597). The area under the curve was 0.89 +/- 0.03 for NT-proBNP to diagnose LVH in the obese HT patients and 0.88 +/- 0.03 in the nonobese. A logistic regression analysis showed that age, gender, and left ventricular mass index (LVMI) were independent predictors of NT-proBNP levels. Body mass index (BMI) was not significantly associated with NT-proBNP in LVH HT patients.. Obesity is not statistically associated with NT-proBNP levels in HT asymptomatic patients. The same results were observed in our group of patients with LVH. These data are in contrast with those previously found in heart failure, and raise questions about the role of obesity per se as primary cause of decreased NT-proBNP levels in other pathophysiological conditions.

Topics: Age Factors; Aged; Biomarkers; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors; ROC Curve; Sex Factors

Hypertension is associated with high cardiovascular risk. Both hsCRP and NT-proBNP also have been associated with elevated cardiovascular risk, at least in the long term. Much less is known about the short-term changes in these markers, for example, in hypertensive emergencies. In 59 consecutive patients with hypertensive emergencies, hsCRP and NT-proBNP were measured at baseline and at days 3-4 and 7-10 after admission. All patients with hsCRP levels above 10 mg/l during the study were excluded due to possible infections. We found elevated levels of hsCRP at baseline with a significant decline on days 3-4 (day 0: median 2.53 mg/l, days 3-4: median 1.65 mg/l [p<0.01 vs. baseline], days 7-10 median: 2.00 mg/l). Women had higher hsCRP levels than men, and patients with hypertensive cardiomyopathy by echocardiographic criteria had significantly higher hsCRP levels compared with patients without hypertensive cardiomyopathy throughout the study. NT-proBNP levels were clearly elevated at admission (median 158 ng/l) and declined highly significantly thereafter (day 3-4: 61 ng/l, p<0.0001 vs. baseline; day 7-10: 76 ng/l, p<0.0001 vs. baseline). Patients with hypertensive cardiomyopathy had higher NT-proBNP levels compared with those patients without. In hypertensive emergencies, NT-proBNP levels correspond to levels described in acute coronary syndrome and decline significantly under antihypertensive therapy. In addition, we found an acute decline in hsCRP in the short term after hypertensive emergencies. These data may have importance in the clinical setting of hypertensive emergencies and in the interpretation of epidemiological data.

Topics: Acute Coronary Syndrome; Aged; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiomyopathies; Echocardiography; Emergencies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Although several risk factors for stroke have been reported in patients with atrial fibrillation (AF), the relation of LV diastolic dysfunction to stroke is still uncertain in these patients. We evaluated the relationship between tissue Doppler-derived index, E/E', as well as other clinical and echocardiographic parameters and ischemic stroke by this cross-sectional study.. Three hundred thirty patients with persistent AF who had preserved LV ejection fraction were included from 6 centers. Clinical data were obtained and standard transthoracic echocardiography was performed. Patients without a history of ischemic stroke (n=280) were compared with patients with this complication (n=50). Potential determinants of ischemic stroke were identified by logistic regression analyses.. In univariate analyses, age, history of hypertension, diabetes mellitus, hyperlipidemia and symptomatic heart failure, plasma brain natriuretic peptide (BNP) level, early mitral inflow velocity (E), diastolic mitral annular velocity (E'), and E/E' ratio were significantly correlated to ischemic stroke. Multivariate regression analyses identified two significant variables that were independently associated with ischemic stroke: hypertension (odds ratio=6.03, p=0.008), and E/E' (odds ratio=1.21, p=0.002).. These findings may have clinical implications that LV diastolic dysfunction, reflected by E/E', is a significant determinant of ischemic stroke in AF. A larger prospective data is needed to confirm the value of E/E' in risk stratification for ischemic stroke in this population.

Topics: Aged; Atrial Fibrillation; Blood Flow Velocity; Cardiac Volume; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Ventricular Dysfunction, Left; Ventricular Function, Left

There is increasing evidence showing that inflammation is involved in heart failure. However, heart failure may differ greatly due to different aetiologies. The role of inflammation in hypertensive heart failure, particularly in the early stage of cardiac dysfunction, has not been studied completely. This study aims at finding out whether inflammation is involved in the early stage of heart dysfunction due to hypertension.. Ten spontaneously hypertensive rats (SHR) and ten age-matched Wistar rats were used. Cardiac morphology and function, as well as coronary flow reserve, were examined by echocardiography. mRNAs for cytokines and brain natriuretic peptide were determined by RT-PCR.. The results demonstrate cardiac hypertrophy with increased heart/body weight ratio in SHR. Echocardiographic examination has shown that SHR developed diastolic heart dysfunction as determined by tissue Doppler without decrease in systolic function. In heart biopsies, there were increased mRNA levels for interleukin-6 and brain natriuretic peptide whereas decreased mRNA for interleukin-2, beta adrenergic receptor, interferon and NFkb in SHR as compared to WKY group. Coronary flow remained unchanged in both groups.. SHR developed cardiac hypertrophy complicated with diastolic heart dysfunction with increased expression of brain natriuretic peptide, down-regulation of beta adrenergic receptors and simultaneous up-regulation of IL-6, which indicates active proinflammatory process as, at least partly, underlying mechanism during the early stage when cardiac hypertrophy associated with diastolic dysfunction occurs.

Topics: Animals; Cardiomegaly; Diastole; Disease Models, Animal; Echocardiography; Gene Expression Regulation; Heart Failure; Hypertension; Hypertrophy; Interleukin-6; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Wistar; Receptors, Adrenergic, beta

Several studies have reported that plasma brain natriuretic peptide (BNP) levels are increased in patients with chronic atrial fibrillation (AF). The objective of this study was to assess the factors influencing plasma BNP levels in patients with chronic AF and preserved left ventricular (LV) systolic function.. Transthoracic echocardiography was performed in 104 patients (48 men, 56 women; mean age, 63.9+/-10.7 years) with chronic AF. At the same time, plasma BNP levels were measured with a Triage kit (Biosite, San Diego, CA).. Women, long duration of AF, and hypertension were more prevalent in the highest quartile group of BNP levels than in the lowest quartile of BNP. Significant correlations were observed between plasma BNP levels and the following: mitral E velocity (r=0.343), mitral annular E' velocity (r=-0.402), ratio of mitral E velocity and mitral annular E' velocity (r=0.487), left atrial(LA) size (r=0.653), LA volume index (r=0.775), right atrial (RA) volume index (r=0.563), maximal velocity (V(max)) of mitral regurgitation (MR) (r=0.448), tricuspid regurgitation (TR) V(max) (r=0.532) and LV mass index (r=0.581). In stepwise multiple linear regression analysis, LA volume index (beta=0.326, p<0.001), LV mass index (beta=0.395, p<0.001) and duration of AF (beta=0.492, p<0.001) independently predicted plasma BNP levels in the study subjects. The patients with increased LA volume index exhibited a longer duration of AF, larger RA volume index and LV mass index, higher MR V(max), TR V(max) and plasma BNP level.. LA volume index, LV mass index and duration of AF are independent predictors of plasma BNP levels in patients with chronic AF and preserved LV systolic function.

Topics: Atrial Fibrillation; Biomarkers; Chronic Disease; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Sex Factors; Ultrasonography; Ventricular Function, Left

Pulmonary arterial hypertension (PAH) is a progressive disease with high mortality. An orally active dual endothelin (ET) receptor antagonist, bosentan, has been reported to improve exercise capacity and survival in patients with PAH. Plasma ET-1 concentration is known to be increased in PAH patients; however, the effect of bosentan on ET-1 concentration has not yet been investigated.. The concentration of ET-1 after bosentan administration was examined in 7 PAH patients, including 2 primary and 5 secondary cases. They were clinically assessed by pulmonary artery pressure (PAP), 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration. Baseline ET-1 concentration was significantly higher in patients with PAH than in normal individuals (2.19+/-0.71 pg/ml vs 1.45+/-0.10 pg/ml, p<0.05) and was significantly correlated with 6MWD and BNP. A single dose of 62.5 mg bosentan in patients with PAH significantly increased plasma ET-1 concentration to 2.04 times the basal concentration (p<0.01) with a peak at 8.1 h. The peak to base ratio of ET-1 after bosentan administration correlated negatively with severity of PAH as assessed by PAP.. The present study is the first study to show that bosentan administration increases plasma ET-1 in patients with PAH. The response of plasma ET-1 to bosentan administration might be useful for determining the severity of PAH.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Bosentan; Case-Control Studies; Endothelin Receptor Antagonists; Endothelin-1; Exercise Test; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Severity of Illness Index; Sulfonamides

Progression of heart failure in hypertensive Dahl rats is associated with cardiac remodeling and increased cardiomyocyte apoptosis. This study was conducted to study whether treatment with a novel inotropic vasodilator compound, levosimendan, could prevent hypertension-induced cardiac remodeling and cardiomyocyte apoptosis.. 6-week-old salt-sensitive Dahl/Rapp rats received levosimendan (0.3 mg kg(-1) and 3 mg kg(-1) via drinking fluid) and high salt diet (NaCl 7%) for 7 weeks, Dahl/Rapp rats on low-salt diet served as controls. Blood pressure, cardiac functions by echocardiography, cardiomyocyte apoptosis by TUNEL technique, tissue morphology, myocardial expression of calcium cycling proteins, and markers of neurohumoral activation were determined.. Untreated Dahl/Rapp rats on high salt diet developed severe hypertension, cardiac hypertrophy and moderate systolic dysfunction. 38% of Dahl/Rapp rats (9/24) survived the 7-week-follow-up period. Cardiomyocyte apoptosis was increased by 6-fold during high salt diet. Levosimendan improved survival (survival rates in low- and high-dose levosimendan groups 12/12 and 9/12, p<0.001 and p=0.05, respectively), increased cardiac function, and ameliorated cardiac hypertrophy. Levosimendan dose-dependently prevented cardiomyocyte apoptosis. Levosimendan normalized salt-induced increased expression of natriuretic peptide, and decreased urinary noradrenaline excretion. Levosimendan also corrected salt-induced decreases in myocardial SERCA2a protein expression and myocardial SERCA2a/NCX-ratio.. Improved survival by the novel inotropic vasodilator levosimendan in hypertensive Dahl/Rapp rats is mediated, at least in part, by amelioration of hypertension-induced cardiac remodeling and cardiomyocyte apoptosis.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Hydrazones; Hypertension; Male; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Norepinephrine; Osteopontin; Pyridazines; Rats; Rats, Inbred Dahl; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Simendan; Sodium-Calcium Exchanger; Vasodilator Agents; Ventricular Remodeling

Hypertension is frequently associated with obesity and natriuretic peptide levels are reported to decrease in obese subjects. Both the lower brain natriuretic peptide (BNP) concentration and insulin resistance are suggested to be associated with hypertension. However, their involvement in obesity-related hypertension has not been clearly defined. Forty-four obese women (21 normotensive and 23 hypertensive) and 25 healthy women matched for age were included in the study. Anthropometrical parameters were determined. Serum BNP, fasting insulin and glucose concentrations, and lipid parameters were evaluated. Insulin resistance was calculated using Homeostasis Model Assessment (HOMA) and Quantative Insulin Sensitivity Check Index (QUICKI) formulations. Within the obese groups, HOMA and QUICKI reflected the increased insulin resistance in hypertensive obese subjects with a significant correlation to blood pressure. The decrease in BNP in the obese groups was in favour of the hypertensive obese subjects (31.43+/-6.43; 26.36+/-4.29; and 17.51+/-3.08 pg/ml, respectively) with a fractional statistical significance between the hypertensive obese group and the controls (P=0.047). Only for the obese hypertensive group, fasting glucose, HOMA and QUICKI were significantly correlated with BNP. Moreover, fasting plasma glucose (R(2)=0.22, P=0.007) and fasting plasma insulin (R(2)=0.39, P=0.03) were independently correlated with BNP only for the obese hypertensive group. It can be concluded that the decrease in BNP concentrations in the obese hypertensive subjects seem to be well correlated with the insulin resistance.

Topics: Adult; Blood Pressure; Case-Control Studies; Female; Humans; Hypertension; Insulin Resistance; Natriuretic Peptide, Brain; Obesity

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia.. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays.. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI.. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placental Circulation; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

Mechanisms purported to contribute to the pathophysiology of heart failure with normal ejection fraction (HFnlEF) include diastolic dysfunction, vascular and left ventricular systolic stiffening, and volume expansion. We characterized left ventricular volume, effective arterial elastance, left ventricular end-systolic elastance, and left ventricular diastolic elastance and relaxation noninvasively in consecutive HFnlEF patients and appropriate controls in the community.. Olmsted County (Minn) residents without cardiovascular disease (n=617), with hypertension but no heart failure (n=719), or with HFnlEF (n=244) were prospectively enrolled. End-diastolic volume index was determined by echo Doppler. End-systolic elastance was determined using blood pressure, stroke volume, ejection fraction, timing intervals, and estimated normalized ventricular elastance at end diastole. Tissue Doppler e' velocity was used to estimate the time constant of relaxation. End-diastolic volume (EDV) and Doppler-derived end-diastolic pressure (EDP) were used to derive the diastolic curve fitting (alpha) and stiffness (beta) constants (EDP=alphaEDVbeta). Comparisons were adjusted for age, sex, and body size. HFnlEF patients had more severe renal dysfunction, yet smaller end-diastolic volume index and cardiac output and increased EDP compared with both hypertensive and healthy controls. Arterial elastance and ventricular end-systolic elastance were similarly increased in hypertensive controls and HFnlEF patients compared with healthy controls. In contrast, HFnlEF patients had more impaired relaxation and increased diastolic stiffness compared with either control group.. From these cross-sectional observations, we speculate that the progression of diastolic dysfunction plays a key role in the development of heart failure symptoms in persons with hypertensive heart disease.

Topics: Adult; Aged; Aged, 80 and over; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Female; Heart Failure; Heart Function Tests; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Reference Values; Stroke Volume

To determine the optimal cut-off values of B-type natriuretic peptide (BNP) for the diagnosis of congestive heart failure (CHF) in 1040 Korean patients with dyspnoea visiting emergency departments.. BNP values were measured for 662 patients without CHF to examine whether significant relationships existed between the BNP values and age, gender or underlying disease. In 378 patients with CHF, a similar analysis was performed in addition to the examination of the relationship between the mean BNP values and CHF severity.. The optimal threshold for the detection of heart failure was a BNP concentration of 296.5 pg/mL, regardless of age, sex and underlying disease among the Korean study population. In the non-CHF patients, women showed significantly higher mean BNP values than did men. Further, in these patients, the mean BNP values of men with underlying disease (hypertension, angina pectoris, chronic renal failure, chronic obstructive pulmonary disease) and those with at least two underlying diseases, one of which was hypertension, was higher than those without underlying disease, whereas no difference was observed between women with and without underlying disease. Based on the New York Heart Association classification, echocardiography findings and mortality rate of the CHF patients, the BNP value was found to be related to both the severity of heart failure and its prognosis.. The BNP concentration used for the diagnosis of CHF in Korean people is considerably higher than the normal cut-off value of 100 pg/mL. In the non-CHF patients, the BNP values of women were influenced less by underlying disease. This suggests that the factors that influence BNP values in women are different from those in men.

Topics: Adult; Age Distribution; Aged; Angina Pectoris; Biomarkers; Comorbidity; Diabetes Mellitus; Dyspnea; Emergency Service, Hospital; Female; Heart Failure; Humans; Hypertension; Korea; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Reference Values; Sensitivity and Specificity; Sex Distribution; Survival Analysis

This study documents the determinants and plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among hypertensive and normotensive subjects in a multi-ethnic population in the United Arab Emirates (UAE). We obtained demographic, anthropometric and clinical data, together with fasting NT-proBNP and biochemical indices from 128 hypertensive patients and 138 normotensive subjects matched for age, gender and ethnicity. Plasma NT-proBNP levels were significantly (P<0.001), and several-fold higher among hypertensives (median 5.92, inter quartile range (IQR): 1.79-18.48 pmol/l) than normotensives (median 1.78, IQR: 0.59-4.32 pmol/l) in the total study population, and the same was true for the ethnic groups separately. Similarly, plasma levels of glucose, blood urea nitrogen (BUN) and creatinine, but not insulin, were significantly (P<0.05) higher among hypertensives than normotensives. For all subjects combined, log NT-proBNP correlated positively and significantly with age (P<0.01), log glucose (P<0.05), systolic blood pressure (SBP, P<0.001), log BUN (P<0.001) and log creatinine (P<0.001). Multivariate regression analysis showed that NT-proBNP levels were independently and positively correlated with SBP, age, gender, log BUN, Emirati and South East Asian ethnic groups and inversely associated with current exercise. In conclusion, we found circulating levels of NT-proBNP to be significantly increased in hypertensive versus normotensive subjects in the UAE and independently related to SBP, age, gender, indices of renal function and possibly exercise. Our results further suggest a possible modulating effect of ethnicity on NT-proBNP levels.

Topics: Adult; Exercise; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; United Arab Emirates

The aim of the work was to study the maintenance of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1 (ET-1) in patients with idiopathic arterial hypertension and the relationships between cardiac morphological parameters and concentrations of examined peptides in group of patients with left ventricular hypertrophy (LVH).. Seventy-six patients were enrolled in the study: 21 patients with confirmed idiopathic arterial hypertension (group 1), 18 with idiopathic hypertension and eccentric hypertrophy (group 1a), 14 with idiopathic hypertension and concentric hypertrophy (group 1b), and 23 patients without arterial hypertension, organic heart disease, or chronic respiratory tract diseases (group 2 - control group). All subjects were submitted for echocardiographic evaluation. Posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDd), left atrium diameter (LAD), left ventricular mass index (LVMI), ejection fraction (EF), fractional shortening (FS), midwall shortening fraction (MWS), and relative wall thickness index (RWT) were studied. Concentrations of ANP(1-28), BNP, and ET-1 were determined with the use of radioimmunological kits (RIA). The obtained results were subjected to statistical analysis.. A considerable increase of ANP and BNP was observed in all patients with hypertension (group 1) in comparison to patients without hypertension (group 2). Significant increases of ANP were found in groups 1a and 1b in comparison to group 1 and 2, as well as considerably increase of BNP in group 1b compared to groups 1, 1a, and 2. In the group of patients with hypertension (group 1), a significant increase in the concentration of ET-1 compared to group 2 was found. However, the concentrations of ET-1 in groups 1 and 2 were not statistically different. Significant differences in concentrations of ET-1 between groups 1a, 1b, and 1 and 2 were seen. Significant correlations were found between concentrations of ANP, BNP, ET-1 and morphological parameters: PWT, IVST, LVMI and RWT. In group 1b, a correlation between concentrations of ANP, BNP, MWS, and LAD was found. The multiple regression analysis showed that RWT independently correlates with concentrations of ANP and BNP, and the concentration of BNP is in closer relation to RWT than ANP. In the case of ET-1, the multiple regression analysis did not show that LVMI or RWT had any independent influence on secretion of ET-1 in patients with idiopathic hypertension and LVH.. Increased concentration of ANP in patients with idiopathic hypertension may point to the coexistence of complications with type of LVH. High concentration of BNP may specifically suggest concentric LVH. This is important - especially if there are difficulties in interpretations of results of other clinical examinations. However, increased concentrations of ET-1 in the plasma of patients with hypertension and LVH should not be treated as an indicator of LVH degree.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Echocardiography, Doppler; Endothelin-1; Female; Heart Atria; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Radioimmunoassay; Severity of Illness Index; Stroke Volume

Brain natriuretic peptide (BNP) acts primarily as a cardiac hormone; it is produced by the ventricle and has both vasodilatory and natriuretic actions. Therefore, the BNP gene is thought to be a candidate gene for essential hypertension (EH). The present study identified variants in the 5'-flanking region of natriuretic peptide precursor B (NPPB) gene and assessed the relationship between gene variants and EH.. The polymerase chain reaction-single strand conformation polymorphism method and nucleotide sequencing were used to identify variants.. A novel variable number of tandem repeat (VNTR) polymorphism in the 5'-flanking region (-1241 nucleotides from the major transcriptional initiation site) was discovered. This VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TTTC. There were 8 alleles, ranging from 9-repeat to 19-repeat. An association study was done involving 317 EH patients and 262 age-matched normotensive (NT) subjects. The 11-repeat allele was the most frequent (88.2%); the 16-repeat allele was the second most frequent (10.5%) in the NT group. The observed and expected genotypes were in agreement with the predicted Hardy-Weinberg equilibrium values (P=0.972). Among females, the overall distribution of genotypes was significantly different between the EH and NT groups (p=0.039). The frequency of the 16-repeat allele was significantly lower in the female EH group (6.5%) than in the female NT group (12.2%, p=0.046).. The 16-repeat allele of the VNTR in the 5'-flanking region of NPPB appears to be a useful genetic marker of EH in females.

Topics: 5' Flanking Region; Adult; Asian People; Base Sequence; Body Mass Index; Female; Gene Frequency; Genotype; Humans; Hypertension; Japan; Linkage Disequilibrium; Logistic Models; Middle Aged; Minisatellite Repeats; Molecular Sequence Data; Natriuretic Peptide, Brain; Phenotype; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Sequence Analysis, DNA

The transcription factors involved in the activation of cardiac gene expression by angiotensin II (Ang II) in vivo are not well understood. Here we studied the contribution of transcriptional elements to the activation of the cardiac B-type natriuretic peptide (BNP) gene promoter by Ang II in conscious rats and in angiotensin II type 1 receptor (AT1R) transgenic mice. Rat BNP luciferase reporter gene constructs were injected into the left ventricular wall. The mean luciferase activity was 1.8-fold higher (P<0.05) in the ventricles of animals subjected to 2-week Ang II infusion as compared with vehicle infusion. Our results indicate that GATA binding sites at -90 and -81 in the rat BNP promoter are essential for the in vivo response to Ang II. The GATA factor binding to these sites is GATA-4. BNP mRNA levels and GATA-4 binding activity are also increased in the hypertrophied hearts of aged AT1R transgenic mice.

Topics: Angiotensin II; Animals; Body Weight; Cells, Cultured; DNA; GATA4 Transcription Factor; GATA6 Transcription Factor; Gene Expression Regulation; Hypertension; Hypertrophy, Left Ventricular; Male; Mice; Mice, Transgenic; Myocardium; Natriuretic Peptide, Brain; Organ Size; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-ets; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; RNA, Messenger; Transcription Factor AP-1; Transcriptional Activation

Patients with an impaired relaxation pattern of Doppler left ventricular filling may have elevated or normal plasma B-type natriuretic peptide (BNP) levels. We hypothesized that elevated BNP levels occur in patients whose left atrial pressure increases after exercise. We examined the relationship between BNP levels and left ventricular filling pressure at rest and immediately after maximal exercise, estimated by Doppler tissue imaging, in 80 patients undergoing exercise echocardiography and showing impaired relaxation pattern. The ratio of early diastolic mitral inflow to annular velocities at rest did not correlate with BNP (r = 0.13, P = .23). In contrast, ratio of early diastolic mitral inflow to annular velocities after exercise correlated with BNP (r = 0.57, P < .001). Ratio of early diastolic mitral inflow to annular velocities after exercise greater than 9.9 discriminated patients with BNP greater than 100 pg/mL (n = 16) from those with BNP less than 100 pg/mL (n = 64) with a sensitivity of 75% and a specificity of 84%. In conclusion, elevated left ventricular filling pressure after maximal exercise predicts increased BNP levels in patients with impaired relaxation pattern.

Topics: Blood Pressure Determination; Exercise Test; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Endurance; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Ultrasonography

The authors examined the relationship of clinic and self-measured pulse pressure with target organ damage in 597 treated hypertensive patients without clinical evidence of renal dysfunction or a history of heart failure. The cross-sectional relationships of plasma brain natriuretic peptide (BNP) and urinary albumin/creatinine ratio with clinic and self-monitored pulse pressures were estimated in age tertile groups: younger than 67 years (n=193), 67 to 75 years (n=216), and older than 75 years (n=188), controlling for various confounding factors. In multivariable analyses, both clinic and self-monitored higher pulse pressures were associated with increased urinary albumin/creatinine ratio in all 3 age groups. Self-monitored higher pulse pressure, but not clinic pulse pressure, was consistently associated with increased BNP in the younger and middle-aged patients. In the very old (older than 75 years), however, there were no consistent associations between pulse pressure measures and BNP. More studies are needed in the evaluation of cardiac risk with hemodynamic measures in the very old.

Topics: Age Factors; Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Creatine; Female; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Statistics as Topic

Diminished nocturnal blood pressure fall in nondipper hypertensive patients are closely associated with poor prognosis. N-terminal probrain natriuretic peptide can also identify poor prognosis in miscellaneous heart diseases. In this study, we aimed to clarify the association between probrain natriuretic peptide levels and diminished nocturnal blood pressure fall in patients with essential hypertension. Twenty-six consecutive nondipper (age: 53+/-8 years, 14 men) (group 1), and 26 dipper hypertensive patients (age: 52+/-9 years, 16 men) (group 2), based on ambulatory blood pressure monitoring, and age and sex-matched 28 normotensive participants (age: 50+/-11 years, 16 men) (group 3) were compared with each other. Although systolic and diastolic ambulatory blood pressure values were similar in hypertensives during the day, those at night were higher in group 1 (P<0.0001). Echocardiographic findings revealed that the left ventricular mass index was higher in both group 1 (184+/-47) and group 2 (142+/-39) compared with control participants (102+/-19) (P<0.0001), but ejection fraction and relative wall thickness were similar in all groups. The transmitral E-wave velocity decreased in group 1 (0.62+/-0.15 m/s) and group 2 (0.7+/-0.14 m/sec) compared with group 3 (0.95+/-0.22 m/s) (P<0.01). The transmitral E/A ratio decreased (0.71+/-0.12, 0.81+/-0.2 and 0.79+/-0.57, respectively P<0.05), and the transmitral E-wave deceleration time increased in group 1 (208+/-46, 203+/-38 and 169+/-42 ms, respectively, P<0.05). The isovolumic relaxation time increased (112+/-23, 110+/-18 and 86+/-11 m/s, respectively, P<0.01). Although group 1 and 2 have a similar number of patients with diastolic dysfunction (23/26 and 22/26, respectively, P>0.05), there were great differences between plasma probrain natriuretic peptide levels (88+/-20, 58+/-22 and 47+/-20 pg/ml, respectively, P<0.0001). In addition, serum uric acid (6.5+/-1.4, 5.3+/-1.5 and 5.0+/-1.9, respectively P<0.001), and creatinine levels (0.88+/-0.2 and 0.78+/-0.2 vs. 0.72+/-0.3, respectively P<0.05) were higher in group 1. These observations suggest that nondipper state may be related to the increase in left ventricular mass index and probrain natriuretic peptide levels and elevation in both plasma uric acid and creatinine levels. Serum probrain natriuretic peptide levels are found to be correlated with left ventricular mass index (Pearson's correlation 469 P<0.0001); but not creatinine (Pearson's correlation 188 P

Topics: Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Disease Progression; Echocardiography; Female; Humans; Hypertension; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Ventricular Function, Left

The antihypertensive and organ-protective effects of the combination of the angiotensin II type 1 receptor blocker losartan and the calcium channel blocker nifedipine were examined in Dahl salt-sensitive rats.. The rats fed with a high-salt diet developed hypertension accompanied by aorta and heart hypertrophy, and impaired renal function. The animals were treated with losartan (30 mg/kg/day), nifedipine (7.8 mg/kg/day) or with a combination of both drugs for 8 weeks. At the end of the study systolic blood pressure, kidney function, organ weight, and mRNA expression were investigated.. Losartan reduced significantly the systolic blood pressure as well as the aorta and left ventricular hypertrophy. Nifedipine and its combination with losartan had similar effects on the systolic blood pressure, aorta and left ventricular hypertrophy but only the combination treatment reduced the expression of transforming growth factor-beta1 in aorta and brain natriuretic peptide in left ventricle significantly. Nifedipine and the combination therapy reduced proteinuria and improved urine creatinine excretion. The expression of collagen III and IV in the kidney was significantly reduced by the combination therapy.. These results indicate that although losartan and nifedipine were effective in lowering blood pressure and showed moderate organ protection, additional benefits can be expected by combination therapy with both compounds.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Blood Pressure; Calcium Channel Blockers; Drug Therapy, Combination; Gene Expression; Hypertension; Hypertrophy, Left Ventricular; Kidney; Losartan; Male; Natriuretic Peptide, Brain; Nifedipine; Organ Size; Rats; Rats, Inbred Dahl; RNA, Messenger; Sodium Chloride, Dietary; Transforming Growth Factor beta1

B-type natriuretic peptide (BNP) is an established biomarker for the differentiation of acute dyspnoea in the emergency department. However, evidence for BNP testing in outpatients is less strong. BNP is not a global test to detect cardiac abnormalities and is only helpful in a few clearly defined clinical settings. Similarly to its use in emergency department patients, BNP is useful in outpatients presenting with dyspnoea to estimate the likelihood of heart failure as the cause of dyspnoea. However, BNP does not provide any reliable information on the underlying cardiac pathology, and in virtually all cases additional examinations are required (primarily echocardiography). In addition, BNP is helpful for risk stratification in patients with heart failure, coronary artery disease and pulmonary artery hypertension.

Topics: Adult; Aged; Ambulatory Care; Cardiovascular Diseases; Coronary Disease; Diagnosis, Differential; Dyspnea; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Ventricular Dysfunction, Left

Cardiovascular disease is a major cause of death in patients on maintenance hemodialysis (HD). Predictors of congestive heart failure (CHF) events in patients on HD were investigated, focusing on left ventricular (LV) function.. One hundred consecutive patients on HD were followed for at least 5 years after index examination performed 1 day after the last HD session. Tests included M-mode and Doppler echocardiography and plasma brain natriuretic peptide (BNP) and hemoglobin (Hb) concentration measurements. Patients with atrial fibrillation or poor echocardiographic images were excluded. Confounding factors included diabetes mellitus (DM), hypertension, age, HD duration, LV fractional shortening, E/A of transmitral flow velocity pattern, Tei index, LV mass index (LVMI), BNP level, Hb, and use of antihypertensive or antiarrhythmic drugs. Six CHF events occurred during 1,703+/-565 days. DM and Hb <10 g/dl were identified as independent predictors of CHF events in a stepwise Cox regression model after DM, LVMI, BNP, and Hb <10 g/dl were selected in the univariate analysis. The hazard ratio (confidence interval) was 10.96 (1.49-80.44) for DM, and 23.00 (2.41-219.76) for Hb <10 g/dl. The estimated hazard across time was constant (T_COV*DM; p=0.726, T_COV*Hb <10 g/dl; p=0.681) by time-dependent covariates analysis.. In patients on maintenance HD, DM and anemia (Hb <10 g/dl), but not echo-derived cardiac function, predicted CHF events.

Topics: Adult; Aged; Anemia; Diabetes Complications; Echocardiography, Doppler; Female; Heart Failure; Hemoglobins; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Ventricular Function, Left

This study was designed to determine how N-terminal pro brain-natriuretic peptide (NT-proBNP) levels correlate with cyclic variation of integrated backscatter (CVIBS) as a reflection of abnormal diastolic function in hypertension.. Forty essentially hypertensive patients were studied. CVIBS values were obtained from the septal wall in the parasternal long-axis view. Twelve had normal diastolic function, 18 had impaired relaxation, and 10 had pseudonormal pattern.. Patients with normal diastolic function had a mean NT-proBNP concentration of 34 +/- 17 pg/ml and a mean CVIBS value of 7.1 +/- 0.9 dB; those with impaired relaxation had a mean NT-proBNP concentration of 71 +/- 25 pg/ml and a mean CVIBS value of 6.7 +/- 1.1 dB. Patients with pseudonormal pattern had the highest NT proBNP levels (206 +/- 75 pg/ml) and lowest CVIBS values (5.7 +/- 0.9 dB). An NT-proBNP value of 62 pg/ml had a sensitivity of 83% and a specificity of 91%; a CVIBS value of 7.2 dB had a sensitivity of 83.3% and a specificity of 66.7% for detecting diastolic dysfunction. An NT-proBNP value of 120 pg/ml had a sensitivity of 76% and a specificity of 96%; a CVIBS value of 6.1 dB had a sensitivity of 87.5% and a specificity of 75% for detecting severe diastolic dysfunction. A close correlation was found between the NT-proBNP and CVIBS values (r: 0.54, P < 0.05).. Combinative use of NT-proBNP and CVIBS can detect the presence of diastolic abnormalities on echocardiography. A good correlation was found between the NT-proBNP and CVIBS values in detecting diastolic dysfunction in essentially hypertensive patients.

Topics: Adult; Area Under Curve; Biomarkers; Diastole; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric

Onset of atrial fibrillation in hypertensive patients is usually associated with a high occurrence of cardiovascular complications. Despite its leading importance as a highly prevalent and modifiable risk factor, only a few data are available regarding the predictors of paroxysmal atrial fibrillation (PAF) in hypertensive patients.. This study was undertaken to determine if PAF could be predicted in hypertensive patients while in sinus rhythm using Doppler-derived indexes and the plasma B-type natriuretic peptide (BNP) concentration.. We prospectively evaluated 165 consecutive patients with hypertension and no known history of PAF or cardiovascular events who attended the cardiology outpatient clinic. Their mean age was 62 +/- 12, 94 male, 71 female. The conventional echocardiographic parameters were measured including: left atrial (LA) volume, mitral regurgitation (MR), left ventricular (LV) function, LV mass. The ratio of transmitral peak E-wave velocity to flow propagation velocity (E/V(p)), ratio of E-wave to mitral annular early diastolic velocity (E/E(a)) obtained by Doppler tissue at the lateral and septal corners of the mitral annulus were calculated. The plasma BNP was measured at the study entry.. After a mean follow-up of 15 +/- 3 months, PAF (symptomatic attacks or documented on the ECG) occurred in 36 (21.8%) of 165 patients. The patients with PAF had significant higher BNP levels than those with sinus rhythm (160 +/- 109.8 vs. 87.9 +/- 57.7 pg/ml, P < 0.001) Also, E/E(a) and E/V(p) ratios were significantly higher in hypertensives with PAF (15.1 +/- 2.8 vs. 8.39 +/- 1.33, P < 0.001), and (1.65 +/- 1.29 vs. 1.19 +/- 1.06, P < 0.001) respectively. In univariate analysis, E/V(p), E/E(a), and BNP and LV hypertrophy were significant predictors of PAF. Barely E/V(p) and E/E(a) remained independently significant after adjustment of clinical and other echocardiographic variables by multivariate logistic regression analysis (odd ratio: 3.36, P < 0.001 and 4.93, P < 0.001 respectively). A cutoff value of > or =1.7 for E/V(p) predicted PAF with 91% sensitivity and 88% specificity; E/E(a) >12 has sensitivity 98%, specificity 89%, while BNP>170 pg/ml has 83% and 72% specificity, respectively, for prediction of PAF in hypertensive patients.. Paroxysmal atrial fibrillation could be predicted in hypertensive patients while in sinus rhythm using Doppler-derived indexes. Increased E/V(p), E/E(a) ratios and elevated BNP appear to be useful parameters to identify patients at heightened risk. They may reflect early left ventricular dysfunction and atrial hypertension in this population.

Topics: Atrial Fibrillation; Blood Flow Velocity; Chi-Square Distribution; Echocardiography, Doppler; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Risk Factors; Statistics, Nonparametric

The aim was to study the maintenance of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with idiopathic hypertension and relationships between cardiac morphological parameters and concentrations of the peptides in patients with hypertension and left ventricular hypertrophy (LVH).. Seventy-six patients were enrolled: 21 with confirmed idiopathic hypertension (group I), 18 with idiopathic hypertension and eccentric hypertrophy (group Ia), 14 with idiopathic hypertension and concentric hypertrophy (group Ib), and 23 healthy controls (group II). All underwent echocardiographic evaluation. Posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular mass index (LVMI), relative wall thickness index (RWT), fractional shortening (FS), midwall shortening fraction (MWS), and left atrium diameter (LAd) were studied.. Considerably increased ANP and BNP were observed in all patients with hypertension (group I) compared with controls (group II). Significant increases in ANP in groups Ia and Ib compared with groups I and II were found as well as considerably increased BNP in group Ib compared with groups I, Ia, and II. Significant correlations were found between ANP and BNP concentrations and PWT, IVST, LVMI, and RWT. In group Ib, correlation between ANP and BNP and MWS and LAd was found. Multiple regression analysis showed that RWT independently correlated with ANP and BNP and that BNP is more closely related to RWT than is ANP.. Increased ANP in patients with idiopathic hypertension may indicate the coexistence of complications with types of LVH. High concentrations of BNP may specifically suggest concentric LVH.

Topics: Atrial Natriuretic Factor; Echocardiography; Female; Heart Atria; Heart Septum; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Regression Analysis

To investigate the effect of PPAR alpha activator fenofibrate on left ventricular hypertrophy and myocardium PPAR alpha (peroxisome proliferator-activated receptor-alpha) expression in spontaneously hypertensive rats (SHR).. Sixteen nine-week-old male spontaneously hypertensive rats were randomly divided into two groups: SHR received fenofibrate 100 mg x kg(-1) x d(-1) by oral gavage once daily for 8 weeks (SHR-F, n=8), and SHR received vechile (0.9 % saline) acted as controls (SHR, n=8). Age-matched Wistar-kyoto rats received vehicle for 8 weeks were served as negative controls (WKY, n=8). Systolic blood pressure was measured at the beginning, 2, 4, and 8 weeks of the experiment. At the end of the experiment, plasma BNP (brain natriuretic peptide)and lipid levels were measured. Left ventricular hypertrophy was accessed by pathological analysis. The expression of PPAR alpha and nuclear factor-kappa B (NF-kappa B p65) were investigated by the method of Western blotting.. Compared with SHR group, systolic blood pressure was slightly lowered in SHR-F group, but it didn't reach significant level(p>0.05). Fenofibrate administration lowered plasma BNP in SHR-F group (P<0.01). There were not much difference of plasma lipid levels between SHR-F and SHR group. Left ventricular mass index (assessed by left ventricular weight/body weight, g x kg(-1)), transdiameter of cardiomyocyte (TDM), cardiomyocyte area (CA), collagen volume fraction (CVF), and perivascular circumferential area (PVCA) decreased significantly in SHR-F group (P<0.05, P<0.01). The myocardium PPAR alpha expression increased significantly (P<0.01), and NF-kappa B p65 expression decreased significantly (P<0.01) in SHR-F group.. PPAR alpha activator fenofibrate can regress left ventricular hypertrophy and increase myocardium PPAR alpha expression in spontaneously hypertensive rats, which is perhaps independent of its lipid-lowering activity.

Topics: Animals; Blood Pressure; Blotting, Western; Fenofibrate; Hypertension; Hypertrophy, Left Ventricular; Lipids; Male; Myocardium; Natriuretic Peptide, Brain; PPAR alpha; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Transcription Factor RelA

Cardiovascular risk markers like microalbuminuria (MAU), highly sensitive C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) currently gain importance to estimate risk in trials and clinical practice. Blockade of the renin-angiotensin system (RAS) has been shown to reduce some of these risk markers in clinical trials, but validation of their time course and role in clinical practice is still pending.. To fill this gap, the design of a nationwide registry study was chosen in which patients attending their cardiologist were observed for 12 months and the effect of blocking the RAS with the angiotensin II receptor blocker irbesartan was documented. Primary question: risk for mortality and the incidence of cardiovascular events in relation to baseline values of MAU, hsCRP, and BNP. Secondary questions: correlations between cardiovascular risk markers (1) amongst each other with respect to cardiovascular events, (2) with clinical findings (echocardiography, electrocardiogram), (3) with the heart rate, (4) with further metabolic parameters (blood sugar, HbA(1c), etc.), and (5) with blood pressure control.. Until April 1, 2006, 2,149 patients were recruited in 305 centers in Germany. Patients had a mean age of 61.4 (+/- 11.3) years. Waist circumference was 103.6 (+/- 13.5) cm. 95.1% of all patients had arterial hypertension at inclusion (> or = 140/90 mmHg). The mean value for albumin/creatinine was 68.9 (+/- 307.5) mg/g (n = 2,100), for hsCRP 4.6 (+/- 8.3) mg/l (n = 2,136), and for proBNP 236.5 (+/- 557.3) pg/ml (n = 2,138).. The present register will elucidate the time course and the interdependence of the cardiovascular risk markers MAU, hsCRP and proBNP as well as their prediction of cardiovascular endpoints in hypertensive individuals. In addition, the role of RAS-blocking agents will be evaluated. A valuable contribution to estimate risk and to optimize care for cardiovascular high-risk patients in clinical practice can be expected.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biphenyl Compounds; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Creatinine; Female; Follow-Up Studies; Germany; Humans; Hypertension; Irbesartan; Male; Middle Aged; Natriuretic Peptide, Brain; Registries; Risk Factors; Survival Rate; Tetrazoles

Beneficial effects of thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, on cardiovascular injuries have been reported. However, the effects of these agonists on left ventricular (LV) hypertrophy have not been clarified. To investigate whether pioglitazone improves LV hypertrophy, we used 32-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) that had been treated or not treated with pioglitazone (10 mg/kg/day) for 8 weeks, and Wistar Kyoto rats (WKY). We evaluated LV geometry by echocardiography; myocyte hypertrophy, tissue fibrosis, and appearance of myofibroblasts by histological examination; mRNA expression by real-time polymerase chain reaction (PCR); protein expression by Western blot; activities of matrix metalloproteinase (MMP) by zymography; and production of reactive oxygen species (ROS) by electron spin resonance spectroscopy or thiobarbituric acid reactive substances (TBARS). SHR-SP showed concentric hypertrophy of the LV, but WKY did not. The myocyte diameter, fraction of tissue fibrosis, and number of myofibroblasts were greater in SHR-SP. mRNA expressions of collagen type I and type III, tissue growth factor (TGF)-beta1, and brain natriuretic peptide (BNP); protein expression of connective tissue growth factor (CTGF); activities of MMP2 and MMP9; and ROS were increased in SHR-SP. Pioglitazone did not decrease blood pressure, but partially normalized LV geometry in addition to decreasing myocyte diameter, interstitial fibrosis and number of myofibroblasts; mRNA levels of collagen type I and BNP; MMP2 activity; and protein level of CTGF. However, the mRNA level of collagen type III and TGF-beta1, MMP9 activity, and ROS production were not improved. In conclusion, pioglitazone reversed the concentric LV remodeling independently from blood pressure or oxidative stress in chronic hypertension.

Topics: Animals; Blood Glucose; Blood Pressure; Collagen Type I; Collagen Type III; Connective Tissue Growth Factor; Echocardiography; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Immediate-Early Proteins; Insulin; Intercellular Signaling Peptides and Proteins; Male; Matrix Metalloproteinases; Natriuretic Peptide, Brain; Organ Size; Pioglitazone; PPAR gamma; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; RNA, Messenger; Thiazolidinediones; Transforming Growth Factor beta1

Pulse pressure (PP) is an independent marker of cardiovascular risk, even in treated hypertensive subjects, but is often little changed by antihypertensive treatment. We assessed the hypothesis that changes in PP during antihypertensive therapy correlate with changes in surrogate markers of target-organ damage.. We studied 540 treated hypertensive subjects whose home systolic blood pressure (SBP) was >/=135 mm Hg. They were followed for 6 months after allocation to either a control group or an added treatment group (doxazosin, 1 to 4 mg plus beta-blocker when needed). The changes in PP and various blood pressure (BP) measures, including mean BP (MP), SBP, and diastolic BP (DBP) during follow-up, were related to changes in plasma B-type natriuretic peptide (BNP) and the urine albumin-creatinine ratio (UAR).. Although self-measured MP was significantly lowered in the added treatment group, PP was not changed overall, although some patients showed a decrease, and others showed an increase. In multivariable analyses, changes in both clinic and home PP were positively associated with changes in log BNP, such that increases in clinic and home PP were paralleled by corresponding increases in BNP. However, no such corresponding relationships were observed when home PP decreased. The change in home PP, but not clinic PP, was positively and linearly associated with the change in UAR.. Changes in PP during antihypertensive treatment are important because PP may increase in some patients, in whom there are adverse changes in surrogate markers of target-organ damage. These changes of PP are best evaluated by home monitoring.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome

A dihydropyridine calcium (Ca) antagonist, azelnidipine (CAS 123524-52-7, Calblock), exhibits hypotensive effects for a prolonged duration, and has been reported to have a strong antiarteriosclerotic action due to its high affinity for vascular tissues and antioxidative action. It has also been reported that azelnidipine does not cause tachycardia associated with the baroreceptor reflex due to vasodilatation. In this study, the antiarteriosclerotic and cardiac hypertrophy-inhibitory effects, and the autonomic nervous activity in essential hypertension of azelnidipine were investigated. The study was performed using the following 2 protocols: 1) Pulse wave velocity (PWV), carotid arterial intima media thickness (IMT), echocardiography, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, brain natriuretic peptide (BNP), and 8-isoprostane were measured after an initial treatment with azelnidipine. 2) The treatment was switched to azelnidipine in patients who had previously been under treatment with amlodipine for essential hypertension, and 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG), measurements of plasma norepinephrine, atrial natriuretic peptide (ANP), and BNP, Holter electrocardiography, and heart rate variability analysis were performed. PWV, IMT, hs-CRP, IL-6, and TNF-alpha significantly decreased. The levels of 8-isoprostane, an antioxidative marker, were also significantly decreased, while adioponectin levels were significantly increased after the initial treatment with azelnidipine. After switching from amlodipine, azelnidipine exhibited a hypotensive effects comparable to amlodipine, and significantly decreased heart rate and the total number of extrasystoles. Noradrenaline levels and the LF/HF ratio were significantly decreased, and the washout rate was significantly reduced on 123I-MIBG myocardial scintigraphy. These findings suggest that azelnidipine inhibits the enhancement of sympathetic nervous activity and the progression of arteriosclerosis through its antioxidative effects.

Topics: 3-Iodobenzylguanidine; Adipokines; Aged; Antihypertensive Agents; Antioxidants; Arteriosclerosis; Autonomic Nervous System; Azetidinecarboxylic Acid; Calcium Channel Blockers; Cardiomegaly; Carotid Arteries; Catecholamines; Cytokines; Dihydropyridines; Electrocardiography; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Pulse; Radionuclide Imaging; Radiopharmaceuticals

Cardiac activator protein-1 (AP-1), composed of c-Jun, is significantly activated by hypertension or angiotensin II (AngII). This study was undertaken to elucidate whether c-Jun could be the potential target for treatment of cardiac hypertrophy. We constructed recombinant adenovirus carrying dominant-negative mutant of c-Jun (Ad.DN-c-Jun). Using catheter-based technique of adenoviral gene transfer, we achieved global myocardial transduction of DN-c-Jun in rats, to specifically inhibit cardiac AP-1. (1) AngII (200 ng/kg/min) infusion in rats caused cardiac hypertrophy, increased cardiac p70S6 kinase activity by 1.3-fold (P<0.05) and enhanced the gene expression of cardiac hypertrophic markers. Ad.DN-c-Jun, which was transferred to the heart 2 days before AngII infusion, prevented cardiac hypertrophy (P<0.01), decreased p70S6 kinase phosphorylation (P<0.05), and suppressed cardiac gene expression of brain natriuretic peptide, collagen I, III, and IV, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) (P<0.01). (2) In genetically hypertensive rats with cardiac hypertrophy, cardiac gene transfer of Ad.DN-c-Jun, without affecting hypertension, regressed cardiac hypertrophy (P<0.05), and suppressed p70S6 kinase phosphorylation by 20% (P<0.05) and suppressed the enhanced expression of collagen I, III, and IV, MCP-1 and PAI-1. These results provided the first evidence that in vivo blockade of cardiac c-Jun inhibits pathologic cardiac hypertrophy.

Topics: Adenoviridae; Angiotensin II; Animals; Blotting, Western; Cardiomegaly; Chemokine CCL2; Collagen Type I; Collagen Type III; Collagen Type IV; Gene Deletion; Genes, Dominant; Genetic Therapy; Genetic Vectors; Hypertension; Injections; Male; Models, Animal; Natriuretic Peptide, Brain; Phosphorylation; Plasminogen Activator Inhibitor 1; Rats; Rats, Sprague-Dawley; Ribosomal Protein S6 Kinases, 70-kDa; Transcription Factor AP-1

The potential use of assays of N-terminal pro-brain natriuretic peptide for detection of diastolic abnormalities associated with alterations in blood pressure has not been elucidated. This study was designed to determine whether increased plasma concentrations of N-terminal pro-brain natriuretic peptide sensitively reflect abnormal diastolic function associated with hypertension.. Concentrations of N-terminal pro-brain natriuretic peptide in plasma were assayed in 40 previously untreated hypertensive patients without overt congestive heart failure and in 20 age and sex-matched controls. Hypertensive patients were studied with the use of pulsed Doppler and color M-mode Doppler echocardiography for the evaluation of left ventricular diastolic function.. Concentrations of N-terminal pro-brain natriuretic peptide were elevated in hypertensive patients [75.1+/-75.2 (SD) pg/ml compared with 37.9+/-38.5 in controls, P<0.05]. In hypertensive patients, concentrations of N-terminal pro-brain natriuretic peptide were negatively correlated with the ratio of color M-mode flow propagation velocity to transmitral E velocity consistent with the view that increased concentrations of N-terminal pro-brain natriuretic peptide are indicative of alterations in diastolic function. Hypertensive patients with N-terminal pro-brain natriuretic peptide values above the mean value in the control group exhibited significantly increased brachial intimal-medial thickness and reduced wall stress, consistent with the view that increased N-terminal pro-brain natriuretic peptide was associated with favorable peripheral arterial remodeling.. Elevated concentrations of N-terminal pro-brain natriuretic peptide in plasma reflect the presence of left ventricular diastolic abnormalities and peripheral arterial remodeling in asymptomatic patients with hypertension.

Topics: Biomarkers; Disease Progression; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Radioimmunoassay; Ventricular Dysfunction, Left

The levels of B-type natriuretic peptide (BNP), a marker of heart failure, are higher in women and anaemic subjects, and tend to be lower in obese people. These relationships are still largely unexplained and it is unclear whether they also apply to the N-terminal portion of BNP precursor (NT-proBNP).. This cross-sectional study was performed to assess general and abdominal obesity, sex and other variables as possible extra-cardiac determinants of NT-proBNP.. A random sample of 713 subjects aged 65-74 years resident of Pianoro (Northern Italy) underwent assessment of NT-proBNP, several haemato-chemical variables, body mass index (BMI), body fat estimation (through skinfold measurement), waist circumference, intra-abdominal thickness and possible presence of hepatic steatosis (by ultrasound examination). An echocardiogram was performed in a subset of 125 subjects. In multivariable analysis NT-proBNP was inversely associated with haematocrit (r=0.22, P<0.0001) and hepatic steatosis (r=0.13, P=0.0001), while no association was found with BMI and body fat estimation. NT-proBNP was higher in women, but this relationship disappeared when haematocrit was included in the multivariable model. The associations with haematocrit and hepatic steatosis were independent from echocardiographic measurements.. NT-proBNP is increased in subjects with low haematocrit, which explains the higher values in women. Although NT-proBNP is not affected by general adiposity, low levels of NT-proBNP are associated with hepatic steatosis.

Topics: Aged; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus; Fatty Liver; Female; Heart Rate; Hematocrit; Humans; Hypertension; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Risk Assessment; Sex Factors; Smoking

Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N-terminal proBNP and BNP.. The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP.. Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L(-1), NS) nor the BNP plasma concentrations (4, 12, 9 pmol L(-1), NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N-terminal proBNP (0.16) was not different from that of BNP (0.16). In contrast, the N-terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0.00 vs. 0.125, P = 0.007).. A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N-terminal proBNP compared with BNP concentrations in normal plasma.

Topics: Aged; Biomarkers; Female; Hemodynamics; Humans; Hypertension; Kidney; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

The diagnosis of left ventricular (LV) hypertrophy, an independent predictor of death and cardiovascular events, is difficult without using echocardiography. This study tested the hypothesis whether C-reactive protein (CRP) and B-type natriuretic peptide (BNP) would be useful to exclude echocardiographic LV hypertrophy. Consecutive hypertensive outpatients were asked to participate. Exclusion criteria were overt heart failure, severe renal insufficiency or any other severe concomitant illness. A venous blood sample was taken to measure plasma CRP and BNP concentrations. Echocardiographic LV hypertrophy was defined as LV mass > or =125 g/m2 for men and > or =110 g/m2 for women. In total, 320 patients were studied, and 37 patients (12%) had echocardiographic LV hypertrophy. Patients with LV hypertrophy were significantly older and had higher CRP and BNP concentrations and higher systolic blood pressure than those without LV hypertrophy. The optimal cut-off points for the diagnosis of LV hypertrophy were 35 pg/ml for BNP (sensitivity 73%, specificity 72%) and 2.5 mg/L for CRP (sensitivity 68%, specificity 59%). Only 1 of 123 patients with values of BNP and CRP less than the optimal cut-off point had echocardiographic LV hypertrophy, resulting in a high negative predictive value of 99% for the 2 blood tests combined to exclude LV hypertrophy. In conclusion, in hypertensive patients, echocardiographic LV hypertrophy can be excluded on the basis of a single blood sample for the determination of BNP and CRP.

Topics: Adult; Area Under Curve; C-Reactive Protein; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity

Adrenomedullin (AM) is a multifunctional regulatory peptide, and endogenous AM is an important factor in regulating cardiovascular and renal homeostasis as a potent cardio-reno-protective factor. To illustrate the protective mechanism of adrenomedullin (AM) on the cardiovascular system by observing (1) the changes in mRNA and protein levels of AM and its receptor-calcitonin receptor-like receptor (CL) and receptor activity-modifying proteins (RAMPs)-in myocardia and aortas of spontaneously hypertensive rats (SHRs) and (2) the response of cardiovascular tissue to AM. The AM content and cyclic adenosine monophosphate (cAMP) production in myocardia and aortas were measured in SHRs and Wistar Kyoto (WKY) rats (11-week-old) by radioimmunoassay (RIA). The mRNA levels of brain natriuretic peptide (BNP), AM, CL, RAMP1, -2, -3 were determined by semi-quantitative RTPCR. Protein levels of CL, RAMP1, -2, -3 were assayed by Western blotting. SHRs had severe hypertension, and the tail-blood pressure was 76.7% higher, the ratio of heart weight to body weight (heart coefficient) 45.5% higher, and the BNP gene expression 4.5-fold higher than that of WKY rats (all p < 0.01). The AM-ir content in plasma, myocardia and aortas of SHRs increased by 42.5%, 68.3% and 80.4%, respectively (all p < 0.01) compared with WKY rats. Furthermore, the mRNA levels of AM, CL, RAMP1, RAMP2 and RAMP3 were elevated by 46% (p < 0.01), 62% (p < 0.05), 51.2% (p < 0.01), 41% (p < 0.01) and 54% (p < 0.01), respectively, in myocardia and by 72%, 87%, 155%, 53% and 74% (all p < 0.01), respectively, in aortas. The elevated mRNA level of CL, RAMP1 RAMP2 and RAMP3 correlated positively with that of AM mRNA in hypertrophic myocardia (r= 0.943, 0.621, 0.688 and 0.633, respectively, all p < 0.01) and aortas (r = 0.762, 0.892, 0.828 and 0.736, respectively, all p < 0.01). The protein levels of CL, RAMP1, RAMP2 and RAMP3 in myocardia and aortas of SHRs were increased compared with that of WKY rats. The response to AM was potentiated in myocardia and aortas in SHRs, and the production of cAMP was increased by 47% and 65% (both p < 0.01), respectively. AM-stimulated cAMP generation in myocardia and aortas was blocked by both AM(22-52), the specific antagonist of AM, and calcitonin gene-related peptide (CGRP)(8-37), the antagonist of the CGRP1 receptor. In myocardia and aortas of SHRs, the gene expressions and protein levels of AM, CL, RAMP1, RAMP2 and RAMP3 were increased, and the response to AM was potentiat

Topics: Adrenomedullin; Animals; Aorta; Blood Pressure; Blotting, Western; Calcitonin Receptor-Like Protein; Cardiomegaly; Cyclic AMP; Hypertension; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Myocardium; Natriuretic Peptide, Brain; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor Activity-Modifying Protein 1; Receptor Activity-Modifying Protein 2; Receptor Activity-Modifying Protein 3; Receptor Activity-Modifying Proteins; Receptors, Calcitonin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

Plasma concentrations of B-type natriuretic peptides (BNP) independently predict the risk of death and cardiovascular events. In the present study, we investigated the intraindividual variability of BNP concentrations, a potential confounder of risk prediction. Consecutive outpatients with blood pressure (BP) values of at least 140/90 mm Hg and not taking BP lowering therapy were asked to participate. Exclusion criteria were renal insufficiency, structural heart disease on echocardiography, except left ventricular hypertrophy and any other severe concomitant illness. Plasma BNP levels were determined on two different days using the same assay. In total, 77 patients were included. Mean age was 54+/-12 years, 55% were male and mean systolic/diastolic BP was 163+/-16/96+/-8 mm Hg. Mean creatinine was 70+/-14 micromol/l. The median interval between the two BNP assays was 10 days (interquartile range 1-23 days). Median BNP concentrations were 17 and 16 pg/ml for the first and second visit, respectively (P=0.48). However, there was a wide range of differences in BNP values among individual patients, 34 patients (44%) having an absolute difference of at least 10 pg/ml. When patients were categorized according to tertiles of BNP levels, 25 (32%) changed from one tertile at the first visit to another at the second visit. In conclusion, these data indicate that BNP levels may be used on a population level. However, the high intraindividual variability seems to preclude useful risk stratification in the individual patient. Care should be taken in the interpretation of single BNP values below the currently accepted thresholds for heart failure.

Topics: Disease Progression; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Factors; Statistics, Nonparametric; Time Factors

Topics: Biomarkers; Cardiovascular Diseases; Disease Progression; Humans; Hypertension; Natriuretic Peptide, Brain; Prognosis; Time Factors

Left atrial (LA) enlargement is an index of adverse cardiovascular events. We sought to investigate any possible correlation between haemodynamic load, neurohumoral factors and LA size in the early stages of essential hypertension.. We studied 94 consecutive middle-aged subjects, with newly diagnosed stage I-II essential hypertension without left ventricular (LV) hypertrophy and 34 age and sex-matched normotensive individuals. Ambulatory blood pressure (BP) monitoring, plasma levels of brain natriuretic peptide (BNP), metabolic profile and left atrial volume index (LAVI), an echocardiographic measurement of LA volume indexed for the body surface area, constituted the work-up of all subjects.. Hypertensive compared with normotensive subjects had significantly increased office and ambulatory systolic and diastolic BP (P < 0.0001 for all cases) as well as body mass index and waist-to-hip ratio (P < 0.05 for both cases). BNP levels were greater in hypertensive compared with normotensive subjects but were not statistically significant (20.4 versus 17.1 pg/ml, P = NS). Hypertensive compared with normotensive subjects also had significantly increased LV mass index (105 versus 84 g/m, P < 0.0001), LA diameter (39 versus 36 mm, P < 0.0001), and LAVI (22 versus 19 ml/m, P < 0.05). In the hypertensive population, LAVI exhibited significant positive relationships with office systolic BP, ambulatory pulse pressure, LV mass index and BNP. In multiple linear regression analysis only LV mass index and BNP were significantly associated with LAVI (beta = 0.298, P = 0.030 and beta = 0.322, P = 0.009, respectively).. Increased LAVI, closely associated with LV mass index and BNP, was still found in the early stages of essential hypertension. However, the clinical significance of these findings remains to be elucidated in future studies.

Topics: Adult; Anthropometry; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Echocardiography; Female; Heart Atria; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors

We evaluated relationships among two circulating molecular forms of brain natriuretic peptide (BNP32 and NT-proBNP), severity of hypertension (HTN), and cardiac hypertrophy in subjects with mild, moderate, and severe HTN. We prospectively studied 78 patients (43 males; mean age 51.4 +/- 11 yr) with essential HTN and 28 age- and sex-matched controls. BNP32 and NT-proBNP were measured by radioimmunoassay. In grade 1 HTN, BNP32 was not elevated and NT-proBNP was reduced (P = 0.030) compared with controls. However, log-transformed values of BNP32 and NT-proBNP were both increased with severity of HTN from grade 1 to 3 (P <0.0001 and P = 0.003, respectively). By multivariate analysis, log BNP32 was independently predicted by age (beta = 0.210, P = 0.026) and HTN grade (beta = 0.274, P = 0.004), whereas log NT-proBNP was independently predicted by sex (beta = 0.235, P = 0.012) and HTN grade (beta = 0.218, P = 0.0023). Two forms of BNP were measured in normal subjects and patients with essential HTN. In grade 1 HTN, BNP32 was unchanged and NT-proBNP was significantly reduced compared with controls. As severity increased in humans with grade 1 to 3 HTN, both BNP32 and NT-proBNP levels were increased while not being affected by the presence of left ventricular hypertrophy. The lack of activation of BNP32 together with the reduction of NT-proBNP in grade 1 HTN may represent an impaired response of the BNP system in the early phase of HTN. The later activation of both forms of BNP may be a late compensatory effect, because it correlates with severity of HTN rather than cardiac hypertrophy/remodeling.

Topics: Blood Pressure; Cardiomegaly; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index; Ventricular Remodeling

We investigated the contribution of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) generation to the pathogenesis of diastolic heart failure (DHF) in Dahl salt-sensitive (DS) hypertensive rats, with the aim of testing our hypothesis that the cardioprotective effects of angiotensin II (Ang II) blockade are provided by the suppression of this pathway.. DS rats were maintained on high (H: 8.0% NaCl) or low (L: 0.3% NaCl) salt diets from age 7 to 17 weeks. DS/H rats were also treated with candesartan cilexetil (10 mg/kg per day, orally) or a superoxide dismutase mimetic, tempol (3 mmol/l in drinking water) from age 7 to 17 weeks.. DS/H rats represented hypertension, left ventricular (LV) relaxation abnormality and myocardial stiffening with preserved systolic heart function. As compared with DS/L rats, DS/H rats showed higher levels of transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), p22phox and gp91phox mRNA expression, NADPH oxidase activity and thiobarbituric acid-reactive substance (TBARS) contents in LV tissues. Gene expression of uncoupling protein-2 (UCP-2), an inner mitochondrial membrane proton transporter, was also 2.8 +/- 0.5-fold higher. In DS/H rats, treatment with candesartan did not alter blood pressure, but resulted in a marked improvement of the hemodynamic deterioration; these therapeutic effects were accompanied by decreases in myocardial NADPH oxidase activity, TBARS contents and the expression of TGF-beta, CTGF, p22phox, gp91phox and UCP-2. Similar therapeutic effects were provided by treatment with tempol in DS/H rats.. Our data suggest that NADPH oxidase-mediated ROS production contributes to the pathogenesis of DHF in DS hypertensive rats, and that the cardioprotective effects of AngII blockade are, at least partially, mediated through the suppression of this pathway.

Topics: Angiotensin II; Animals; Blood Pressure; Collagen; Connective Tissue Growth Factor; Diastole; Gene Expression; Heart Failure; Heart Ventricles; Hypertension; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Ion Channels; Lung; Male; Membrane Transport Proteins; Mitochondrial Proteins; Myocardium; NADPH Oxidases; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Inbred Dahl; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Transforming Growth Factor beta; Uncoupling Protein 2; Ventricular Dysfunction, Left

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.

Topics: Albuminuria; Antihypertensive Agents; Blood Pressure Determination; Circadian Rhythm; Clinical Protocols; Creatine; Doxazosin; Humans; Hypertension; Japan; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF).. Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients.. We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay.. Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects.. These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.

Topics: Adult; Aged; Blotting, Western; Cardiac Volume; Collagen; Female; Heart Failure; Humans; Hypertension; Immunohistochemistry; Male; Matrix Metalloproteinase 1; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Systole; Tissue Inhibitor of Metalloproteinase-1; Ventricular Function, Left

The purpose of the study was to assess the effect of percutaneous transluminal coronary angioplasty (PTCA) on plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level in hypertensive and normotensive subjects with and without systolic left ventricular dysfunction.. Forty patients affected by ischemic heart disease and submitted to PTCA were studied. The patients were divided into four groups: group I - 10 patients with essential arterial hypertension (HT) and normal left ventricular ejection fraction (EF); group II - 10 patients with HT and EF < 55%; group III - 10 patients without HT and with normal EF; group IV - 10 patients without HT and with EF < 55%. Blood samples were collected twice: 24 h before and after PTCA. The plasma NT-proBNP concentrations increased significantly in group I (368+/-103 pg/ml vs 488 +/- 182 pg/ml; p < 0.05), in group III (257 +/- 107 pg/ml vs 447 +/- 198 pg/ml; p < 0.05), and in group IV (419 +/- 99 pg/ml vs 826 +/- 432 pg/ml; p < 0.05) 24 h after PTCA. There were significant differences in the relative change in plasma NT-proBNP concentrations between groups I and II, and between groups III and IV.. Successful coronary angioplasty results in a rise in plasma NT-proBNP concentration. The increase is less expressive in patients with systolic left ventricular dysfunction. The presence of hypertension does not affect NT-proBNP concentration after PTCA.

Topics: Aged; Angioplasty, Balloon, Coronary; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Dysfunction, Left

The goal of our study was to investigate the relationships between atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and type A natriuretic peptide receptor (NPRA) gene polymorphisms and left ventricular structure in human essential hypertension.. Experimental evidence supports a key role for natriuretic peptides in the modulation of cardiac mass. This relationship has not yet been described in human disease.. A total of 203 hypertensive patients were studied by mono-bidimensional echocardiography. Three markers of the ANP gene (-C664G, G1837A, and T2238C polymorphisms) and a microsatellite marker of both NPRA and BNP genes were characterized.. Patients carrying the ANP gene promoter allelic variant had increased left ventricular mass index (117.4 +/- 1.7 g vs. 95.7 +/- 1.7 g, p = 0.005), left ventricular posterior wall thickness (1.14 +/- 0.07 cm vs. 0.96 +/- 0.01 cm, p < 0.0001), left ventricular septal thickness (1.12 +/- 0.10 cm vs. 1.04 +/- 0.01 cm, p = 0.01), and relative wall thickening (47.5 +/- 4.1% vs. 39.4 +/- 5.3%, p = 0.001) as compared with the wild-type genotype. These associations were independent from anthropometric factors and major clinical features and were confirmed in a large subgroup of never-treated hypertensive patients (n = 148). Carrier status of the ANP gene promoter allelic variant was associated with significantly lower plasma proANP levels: 1,395 +/- 104 fmol/ml versus 3,110 +/- 141 fmol/ml in hypertensive patients carrying the wild-type genotype (p < 0.05). A significant association for NPRA gene variants with left ventricular mass index and left ventricular septal thickness was found. The analysis of BNP did not reveal any effect on cardiac phenotypes.. Our findings show that the ANP/NPRA system significantly contributes to ventricular remodeling in human essential hypertension.

Topics: Adenine; Adult; Alleles; Atrial Natriuretic Factor; Cytosine; Echocardiography; Female; Genetic Variation; Guanine; Guanylate Cyclase; Heterozygote; Homozygote; Humans; Hypertension; Hypertrophy, Left Ventricular; Introns; Male; Natriuretic Peptide, Brain; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Atrial Natriuretic Factor; Thymine; Ventricular Remodeling

Arterial hypertension has been associated with increased plasma concentrations of C-reactive protein (CRP) and B-type natriuretic peptide (BNP). This study tested the hypothesis that patients with white coat hypertension have lower plasma CRP and BNP concentrations than those with sustained hypertension. A total of 109 consecutive medical outpatients with never-treated office hypertension underwent ambulatory blood pressure monitoring and blood sampling to determine CRP and BNP concentrations. Patients with treated hypertension, lipid-lowering therapy, renal insufficiency or structural heart disease other than left ventricular hypertrophy were excluded. White coat hypertension was defined as office hypertension associated with mean daytime blood pressure values below 135/85 mmHg. A control group of 48 consecutive, age- and sex-matched patients without office hypertension were recruited during the same period. Twenty-six patients (24%) had white coat hypertension. There were no statistically significant differences in baseline variables between patients with sustained hypertension and white coat hypertensives, except for mean blood pressure values. Mean CRP was 3.2+/-5.1 mg/l in patients with white coat hypertension compared to 3.4+/-4.2 mg/l in those with sustained hypertension (p=0.79). Control patients had significantly lower CRP values than patients with either white coat or sustained hypertension (1.2+/-0.9 mg/l, p=0.002 and p=0.038, respectively). Mean BNP concentrations were 21+/-25 pg/l and 44+/-125 pg/l in white coat and sustained hypertensives, respectively (p=0.36). The plasma concentrations of CRP and BNP did not differ between patients with white coat hypertension and those with sustained hypertension.

Topics: Adult; Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Case-Control Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Office Visits

The physiologic properties of the b-type natriuretic peptide nesiritide include pulmonary, coronary, and renal arterial vasodilation and lusitropic effects on ventricular myocardium. These effects may be useful during cardiac surgery, particularly when myocardial function and cardiac output (CO) are compromised. Intraoperative hemodynamic data were collected retrospectively before and 5-15 min following completion of a nesiritide loading dose in 15 adult cardiac surgical patients with low CO associated with pulmonary hypertension, low left ventricular ejection fraction, diastolic dysfunction, or left ventricular assist device placement. In seven patients, prior alternative pharmacologic interventions had failed to improve CO, and fluid challenges were ineffective in six patients with diastolic dysfunction. Perioperative nesiritide administration (2 microg.kg(-1) load, followed by 0.01 microg.kg(-1).min(-1) for a maximum of 24 h) resulted in a statistically significant median increase in CO of 35% (P = 0.0006). In conclusion, nesiritide was associated with increased CO in patients with low CO syndromes undergoing cardiac surgery, when other measures failed. This novel agent may offer an additional option to inotropes and fluid challenges for these patients perioperatively. Randomized clinical trials are desirable to determine the risks and benefits of nesiritides and to elucidate its role for the cardiac anesthesiologist.

Topics: Aged; Aged, 80 and over; Carbon Monoxide; Cardiac Output, Low; Cardiac Surgical Procedures; Echocardiography, Transesophageal; Female; Heart-Assist Devices; Humans; Hypertension; Male; Middle Aged; Monitoring, Physiologic; Natriuretic Agents; Natriuretic Peptide, Brain; Perioperative Care; Retrospective Studies

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful predictor of cardiovascular events in patients without clinical evidence of cardiovascular disease. It is unknown if the cardiovascular risk factors control can modify these levels. We studied if atorvastatin treatment decrease NT-proBNP levels in hypercholesterolemic subjects, with and without hypertension.. It was an open, prospective study in 39 patients with hypercholesterolemia without clinical evidence of cardiovascular disease. 15 (38.5%) had hypertension. Blood samples were collected initially and 12 and 24 weeks after beginning treatment with 20 mg of atorvastatin.. The median age was 54 years, and 41% were males. NT-proBNP (pg/ml) values were: 193 (294) at baseline; 141 (211) (p < 0.05) after 12 weeks therapy, and 89 (130) (p < 0.01) at 24 weeks. In hypertensive patients value changed from: 275 (388) at baseline, 196 (290) (p < 0.05) and 112 (124) (p < 0.001) after 12 and 24 weeks treatment. And the levels in normotensives patients were: 137 (198) at baseline, 103 (129) (p = NS), and 74 (135) (p < 0.001) at 12 and 24 weeks after treatment with atorvastatin. We didn't find any correlations between the percentage decrease in NT-proBNP levels, and change of total cholesterol, systolic blood pressure, C reactive protein, or nitrites/nitrates blood levels, at 12, and 24 weeks compared to baseline levels.. In middle-aged hypercholesterolemic patients, without evidence of cardiovascular disease, atorvastatin therapy decrease NT-proBNP blood levels, in both hypertensive and normotensives subjects.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pyrroles

Our hypothesis states that the reactivity of the cutaneous microcirculation is reduced in patients with hypertension compared with healthy subjects. The objective was to verify the hypothesis by measuring microvascular function in hypertensive patients.. The study was a controlled trial with two arms: 15 hypertensives and 15 normotensives were enrolled, aged 30-60 years, and in hypertensives, a diastolic blood pressure of > 90 mmHg. The hypertensive patients were compared with gender- and age-matched controls having a diastolic blood pressure < 90 mmHg. The patients were kept on their medication.. The local cutaneous forearm blood flow was measured by Laser-Doppler flowmetry. The blood flow response to local warming (44 degrees C), to the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) administered by iontophoresis were determined. Inflammatory markers and NT-pro brain natriuretic peptide (NT-proBNP) levels in plasma was also measured. Electrocardiograms (ECG) were evaluated and the subjects answered a lifestyle questionnaire.. The percentage change in vasodilator response to CGRP was significantly lower in the hypertensives compared with normotensives, 285% (95% CI 86-484) vs 764% (95% CI 366-1162) of baseline, p < 0.05. The change to local warming was 2191% (95% CI 1574-2807) in normotensives vs 1384% (95% CI 852-1917) in the hypertensives, p < 0.05. The vasodilator response to ACh was 1249% (95% CI 895-1602) in the normotensives and 873% (95% CI 610-1136) in the hypertensives. The vasodilator response to SNP in the normotensives was 771% (95% CI 436-1107) and 682% (95% CI 416-948) in the hypertensive group. Plasma level of NT-proBNP was 90 ng/1 (95% CI 35-145) in normotensives vs 285 ng/l (95% CI 70-499) in hypertensives (p = 0.06). The ECGs showed a tendency towards left ventricular hypertrophy (LVH) in hypertensives.. Patients with essential hypertension had significantly reduced microvascular dilator responses to CGRP and to local warming. Also, there was a tendency towards reduced responses to ACh. This points towards a generally weaker responsiveness of the cutaneous microvessels in hypertensives and could be a contributing factor to the development of high blood pressure. Patients with essential hypertension also had a tendency of higher plasma levels of NT-proBNP, which could be seen as an early sign of organ damage.

Topics: Acetylcholine; Adult; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Forearm; Hot Temperature; Humans; Hypertension; Male; Microcirculation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Skin; Vasodilation

Brain natriuretic peptide (BNP) has important role in the diagnosis and management of heart failure. Data on the impact of blood pressure (BP) on BNP are controversial. In primary aldosteronism (PA), BNP production can be affected by both hypertension and specific endocrine mechanisms. This study was aimed at investigating the impact of hypertension and hyperaldosteronism on plasma BNP levels.. Plasma BNP concentration, casual and 24-h BP and echocardiographic indices were assessed in 40 patients with moderate to severe essential hypertension (EH), 40 BP-matched patients with PA, and 40 age- and sex-matched healthy controls.. BNP levels in PA and EH groups did not differ significantly and were higher compared with those in controls [median and interquartile range 26 (13-48) pg/ml, p = 0.01, and 23 (9-32) pg/ml, n.s., vs 14 (6-26) pg/ml in controls]. Remarkably elevated BNP was observed only in three PA and two EH patients, all having significant left ventricular (LV) hypertrophy. BNP levels in PA and EH groups correlated weakly with casual and 24-h BP, interventricular septal thickness and LV mass index (LVMI). Diastolic BP and LVMI were identified as the strongest independent determinants of BNP (p = 0.002 and p = 0.01, respectively).. Both PA and EH patients had modest and mutually comparable elevation of BNP, which was independently determined by diastolic BP and LVMI. Both subtypes of PA (aldosterone-producing adenoma and bilateral adrenal hyperplasia) had similar effect on BNP production. Specific impact of hyperaldosteronism on BNP was not confirmed.

Topics: Adult; Aged; Blood Pressure; Case-Control Studies; Diastole; Electrocardiography; Female; Humans; Hyperaldosteronism; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain

There are few community-based epidemiologic studies that have dealt with risk factors for heart failure in non-Western populations. It has been reported that the measurement of plasma B-type natriuretic peptide (BNP) is useful for detecting patients with asymptomatic heart failure. To clarify the determinants of high plasma BNP level, the association of BNP with cardiovascular risk factors in community dwelling residents was examined. The plasma BNP levels were measured in 686 residents aged 35-69 years who received annual health check-up. The relationship of BNP to blood pressure, blood haemoglobin, serum cholesterol (total and high-density lipoprotein cholesterol), plasma glucose, electrocardiographic (ECG) findings, urinary salt excretion, and lifestyle factors (smoking and alcohol consumption) were cross-sectionally analysed. The plasma BNP geometric mean was 13.7 pg/ml. Both linear and logistic regression analyses indicated that the plasma BNP levels were positively associated with age, urinary salt excretion, higher blood pressure, high R-wave voltage in the 12-lead ECG (Minnesota Code 3-1 or 3-3), and female gender. Plasma BNP levels were inversely associated with blood haemoglobin levels. Gender-specific analysis showed similar results. However, plasma BNP did not correlate with other cardiovascular risk factors such as serum lipids.

Topics: Adult; Age Factors; Aged; Blood Pressure; Electrocardiography; Female; Humans; Hypertension; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sex Factors; Sodium Chloride, Dietary

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Case-Control Studies; Cerebrovascular Disorders; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Perindopril; Predictive Value of Tests; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity; Stroke

Acute blood pressure (BP) elevation and cardiac abnormalities are known to follow ischemic stroke. Brain natriuretic peptide (BNP), which is produced in response to such cardiovascular alterations, is expected to play a hemodynamic role. We measured plasma BNP concentrations in patients with cerebral infarction (CI) to determine the implications of BNP in acute ischemic stroke.. Eighty-eight patients with CI, 59 with essential hypertension, 44 with spontaneous intracerebral hemorrhage, 22 with asymptomatic atrial fibrillation (Af), and 20 age- and sex-matched healthy volunteers were recruited in the study. CI patients were divided into 2 subgroups either having Af (27 patients) or not (61 patients). BNP levels were repeatedly measured in 58 patients with CI. BNP levels were compared between ischemic subgroups categorized by size of infarction. Correlation was investigated between BNP levels and hemodynamic parameters.. BNP levels in CI patients were significantly higher, but they decreased in the subacute period. BNP levels in CI patients without Af were correlated with mean arterial blood pressure (MAP) on admission or the degree of reduction in MAP at day 1, while in CI patients with Af BNP levels showed negative correlation with MAP on admission. Follow-up serum sodium levels in CI patients with Af were negatively correlated with BNP levels on admission.. This study suggests the hemodynamic implications of BNP in acute ischemic patients.

Topics: Acute Disease; Aged; Atrial Fibrillation; Blood Pressure; Brain Ischemia; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sodium; Stroke; Water-Electrolyte Balance

A significant number (20% to 40%) of hypertensive patients with renal artery stenosis will not have blood pressure improvement after successful percutaneous revascularization. Identifying a group of patients with refractory hypertension and renal artery stenosis who are likely to respond to renal stent placement would be beneficial.. Brain natriuretic peptide (BNP) was measured in 27 patients with refractory hypertension and significant renal artery stenosis before and after successful renal artery stent placement. This neuropeptide was elevated (median, 187 pg/mL; 25th to 75th percentiles, 89 to 306 pg/mL) before stent placement and fell within 24 hours of the successful stent procedure (96 pg/mL; 25th to 75th percentiles, 61 to 182 pg/mL; P=0.002), remaining low (85 pg/mL; 25th to 75th percentiles, 43 to 171 pg/mL) at follow-up. Clinical improvement in hypertension was observed in the patients with a baseline BNP >80 pg/mL (n=22) in 17 patients (77%) compared with 0% of the patients with a baseline BNP < or =80 pg/mL (n=5) (P=0.001). After correction for glomerular filtration rate, BNP was strongly correlated with improvement in hypertension.. BNP is increased in patients with severe renal artery stenosis and decreases after successful stent revascularization. In addition, an elevated baseline BNP level of >80 pg/mL appears to be a good predictor of a blood pressure response after successful stent revascularization.

Topics: Aged; Biomarkers; Blood Pressure; Female; Glomerular Filtration Rate; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Renal Artery Obstruction; Stents; Vascular Surgical Procedures

Nesiritide is a recombinant formulation of B-type natriuretic peptide (BNP). Preliminary experience in the adult population has shown nesiritide to be an effective agent in the treatment of decompensated congestive heart failure (CHF) in adults. Given its physiological effects, it may be an effective agent in other clinical scenarios. We report the use of nesiritide in two infants during extracorporeal membrane oxygenation (ECMO). In one patient, nesiritide in doses up to 0.09 microg.kg(-1).min(-1) were used to control mean arterial pressure while in the other patient, doses of 0.01-0.03 microg.kg(-1).min(-1) were used to augment urine output. The potential applications of nesiritide and dosing regimens for this agent in the ECMO population are discussed.

Topics: Blood Pressure; Cardiopulmonary Resuscitation; Dose-Response Relationship, Drug; Electrocardiography; Extracorporeal Membrane Oxygenation; Fatal Outcome; Heart Diseases; Heart Ventricles; Hernia, Diaphragmatic; Humans; Hypertension; Hypokinesia; Hypoplastic Left Heart Syndrome; Infant, Newborn; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Respiratory Insufficiency; Urination

We recently showed that plasma concentration of N-terminal atrial natriuretic peptide (Nt-proANP) is strongly directly related to salt sensitivity. The aims of the present study were to test (i) whether plasma concentration of N-terminal brain natriuretic peptide (Nt-proBNP) is related to salt sensitivity and (ii) whether Nt-proANP, as a marker of salt sensitivity, differs between type 2 diabetes patients and nondiabetic subjects without a history of coronary heart disease.. Nt-proBNP was determined in 30 Swedish normal subjects with heredity for primary hypertension and salt sensitivity was defined as the difference between mean arterial blood pressure after 1 week on a high-salt diet (240 mmol day(-1)) and 1 week on a low-salt diet (10 mmol day(-1)). Nt-proANP was measured in 253 patients with type 2 diabetes and in 230 nondiabetic subjects aged 40-70 years, all without a history of coronary heart disease.. Amongst the 30 subjects, in whom salt sensitivity was directly measured, Nt-proBNP was not correlated with salt sensitivity (R=-0.18, P=0.35). Nt-proANP (median, interquartile range) was lower in patients with type 2 diabetes (505, 387-661 pmol L(-1)) than in nondiabetic subjects (536, 421-696 pmol L(-1)) (P=0.02). In a multiple regression analysis heart rate (P <0.00001), diastolic blood pressure (P=0.02) and diabetes status (P=0.02) were inversely related whereas age (P <0.00001), cystatin C (P=0.0006), hypertension treatment (P=0.002) and female sex (P=0.006) were directly related to ln(Nt-proANP).. In contrast to Nt-proANP, Nt-proBNP is not related to salt sensitivity. Salt sensitivity, as estimated by Nt-proANP, seems to be reduced in type 2 diabetes.

Topics: Atrial Natriuretic Factor; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Sodium Chloride, Dietary

This study was designed to investigate whether plasma concentration of cardiotrophin-1 (CT-1), a cytokine that induces cardiomyocyte hypertrophy and stimulates cardiac fibroblasts, is related to hypertensive heart disease, as defined by the presence of echocardiographically assessed left ventricular hypertrophy (LVH).. The study was performed in 31 normotensive subjects and 111 patients with never-treated essential hypertension (54 without LVH and 57 with LVH). Causes of LVH other than hypertension were excluded after a complete medical workup. A novel enzyme-linked immunosorbent assay was developed to measure plasma CT-1.. Plasma CT-1 was increased (P < 0.001) in hypertensives compared with normotensives. The value of CT-1 was higher (P < 0.001) in hypertensives with LVH than in hypertensives without LVH. Some 31% of patients without LVH exhibited values of CT-1 above the upper normal limit in normotensives. A direct correlation was found between CT-1 and left ventricular mass index (r = 0.319, P < 0.001) in all subjects. Receiver operating characteristic curves showed that a cutoff of 39 fmol/ml for CT-1 provided 75% specificity and 70% sensitivity for predicting LVH with a relative risk of 6.21 (95% confidence interval, 2.95 to 13.09).. These results show an association between LVH and the plasma concentration of CT-1 in essential hypertension. Although preliminary, these findings suggest that the determination of CT-1 may be an easy and reliable method for the initial screening and diagnosis of hypertensive heart disease.

Topics: Animals; Antibodies; Biomarkers; Blood Pressure; Cytokines; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Fibrosis; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Procollagen; Rabbits; ROC Curve

Patients with hypertension are at high risk for the development of left ventricular dysfunction (LVD). Echocardiography is considered to be the gold standard for diagnosis of LVD; but its cost, complexity, and availability prevents its use for frequent evaluation. Brain natriuretic peptide (BNP) and N-terminal BNP (NT-BNP) can identify heart failure in dyspneic patients. Impedance cardiography (ICG) is a noninvasive method of measuring hemodynamic and electromechanical timing parameters. The objective of this study was to determine the ability of BNP, NT-BNP, and ICG to detect the presence of LVD in patients with hypertension.. A convenience sample of subjects undergoing echocardiography who had a history of hypertension or current systolic blood pressure >/=140 mm Hg were enrolled and retrospectively evaluated. Patients with known LVD were excluded. Diagnosis of LVD was determined by the presence of systolic or diastolic dysfunction, valvular or wall motion abnormalities, or left ventricular hypertrophy.. A total of 193 subjects were enrolled: 189 men and four women, age 68.8 +/- 11.7 years. Multivariate regression analysis of history and symptoms, BNP, and ICG parameters identified significant predictor variables for LVD including cardiac index (P = .005), left cardiac work index (P = .008), BNP (P = .017), arrhythmia (P = .023), angina (P = .034), and systemic vascular resistance (P = .048). Receiver operating characteristic (ROC) analysis determined the area under the ROC curve (AUC) of BNP (0.60), NT-BNP (0.67), ICG velocity index (0.66), composite ICG (0.66), ICG combined with BNP (0.70), and ICG combined with NT-BNP (0.73).. In this high-risk hypertensive population, BNP, NT-BNP, and ICG were useful to identify the presence of LVD. The use of ICG with natriuretic peptide testing may improve the ability to detect LVD.

Topics: Aged; Area Under Curve; Cardiography, Impedance; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Retrospective Studies; ROC Curve; Ventricular Dysfunction, Left

In this study, it was found that increased plasma B-type natriuretic peptide (BNP) levels in patients with diabetes may be related to left ventricular (LV) diastolic relaxation, independent of LV mass and atherosclerosis (using common carotid intima-media thickness as a surrogate index). A "package of care" of glycemic control and cardiovascular risk management was not associated with reduction in BNP levels.

Topics: Aged; Diabetes Complications; Diastole; Echocardiography, Doppler; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD. We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 microg of FGF-2 plus 1.28 microg of heparin (n = 6), 100 microg of FGF-2 (n = 6), 1.28 microg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline. These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography; Fibroblast Growth Factor 2; Heart Failure; Heart Rate; Heparin; Hypertension; Hypertrophy, Left Ventricular; Injections; Male; Myocardium; Natriuretic Peptide, Brain; Neovascularization, Pathologic; Rats; Rats, Inbred Dahl; Ventricular Function

Topics: Adult; Biomarkers; Case-Control Studies; Chronic Disease; Disease Progression; Echocardiography, Doppler; Female; Heart Failure; Heart Function Tests; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

To assess relationships between noninvasive ambulatory blood pressure (BP), clinic BP (mean value of three readings in the seated position measured by nurses), structural cardiac indices, intima-media thickness of the common carotid artery and several hormones.. Cross-sectional study of 75 subjects with hypertension and left ventricular hypertrophy (HTH) according to echocardiography, 35 subjects with hypertension and normal left ventricular dimensions (HT) and 23 normotensive subjects (NT).. We found an excellent correlation between mean 24-h ambulatory BP and clinic BP, the r-value for systolic BP being 0.82 and for diastolic levels 0.78 (both P < 0.0001). Clinic and ambulatory BP correlated equally well with left ventricular (LV) mass index (r-values between 0.55 and 0.64, all P < 0.0001) and to intima-media thickness of the carotid artery (r = 0.18-0.34, P < 0.01). The systolic white-coat effect (clinic BP - day-time BP) was higher in the HTH and HT compared with NT and was weakly correlated to LV mass index (r = 0.18, P = 0.04). Nondippers (mean arterial night/day BP ratio of > 0.9) had higher brain (6.1 +/- 7.5 pmol L(-1) vs. 3.7 +/- 3.2 pmol L(-1), P = 0.01) and atrial (14 +/- 3.4 pmol L(-1) vs. 9.3 +/- 5.4 pmol L(-1), P = 0.04) natriuretic peptide levels, and also exhibited a lower ejection fraction (49 +/- 8% vs. 57 +/- 9%, P = 0.006), than dippers.. Clinic BP recordings performed by nurses as three measurements 1 min apart provide excellent relationship to target organ damage. Nondippers exhibited signs of a more advanced hypertensive organ damage than dippers which corresponds well with the poor prognosis linked to this condition.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Carotid Artery, Common; Cross-Sectional Studies; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Nursing Care

N-terminal pro-brain natriuretic peptide (NT-proBNP) provides important prognostic information in patients with chronic heart failure and in the general population. The aim of this study was to evaluate NT-proBNP as a prognostic marker of cardiovascular morbidity and death in a sample of subjects with hypertension and preserved left ventricular systolic function from the general population.. The study population was recruited from 4 general practitioners. The study participants (n = 569 subjects; ages, 50-89 years) completed a heart failure questionnaire and were submitted to blood pressure measurement, electrocardiography, echocardiography, and blood sampling. After exclusion of subjects with left ventricular ejection fraction of <50%, 270 subjects fulfilled the following criteria for hypertension: history of hypertension or blood pressure >150/90 mmHg. During 3 years of follow-up, 28 subjects (10.4%) reached the composite end point of death, stroke/transient ischemic attack, or myocardial infarction. After adjustment for cardiovascular risk factors, NT-proBNP (logarithmically transformed) independently predicted the risk of experiencing a composite end point (hazard ratio, 1.94; P < .0001), and death (hazard ratio, 2.28; P < .0001). The risk of having a composite end point (21 vs 7; P = .005) was significantly higher for subjects with NT-proBNP above the study median than for subjects with NT-proBNP below the study median.. In this sample of subjects with hypertension and preserved left ventricular systolic function from the general population, plasma NT-proBNP was found to be a valuable cardiovascular risk marker, independently of traditional risk factors and prevalent cardiovascular disease.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Pressure Monitors; Cardiovascular Diseases; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Prognosis; Stroke Volume; Surveys and Questionnaires

To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1 receptor blockers (ARBs) have different abilities to attenuate progressive cardiac hypertrophy despite their comparable lowering of blood pressure, we compared the effect of these agents alone or in combination on hypertensive cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were divided into 7 groups. Single administration of doxazosin, atenolol, or losartan, or half-dose combinations of these drugs were given orally for 6 weeks. The control group did not receive any drugs. The heart weight-to-body weight ratio (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide (BNP) and left ventricular BNP mRNA expression were measured after 6-week administration. Blood pressure did not differ among the drug-treated groups, all of which showed lower blood pressure than the control group. The HW/BW and LVMI of the drug-treated groups, except the doxazosin group, were lower than in the control group. Moreover, the LVMI values of the groups receiving losartan were significantly lower than those in the groups without losartan (p < 0.05). Plasma BNP of the drug-treated groups was lower than that in the control group (p < 0.05). The left ventricular BNP mRNA expression of the drug-treated groups, except the doxazosin group, was lower than that in the control group. The atenolol group showed a higher level of BNP mRNA than the groups receiving losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB had the strongest attenuating effect on the development of hypertensive cardiac hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more effective in combination than as monotherapies in SHR.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Atenolol; Blood Pressure; Cardiomegaly; Doxazosin; Drug Therapy, Combination; Echocardiography; Heart Rate; Hypertension; Losartan; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; RNA, Messenger

Cardiotrophin-1 (CT-1) is an interleukin-6-related cytokine with known hypertrophic and protective actions upon cardiac myocytes. We provide here the first report of cardiac tissue and plasma levels of CT-1 in human and experimental hypertension, demonstrate cardiac CT-1 secretion stimulated by ventricular stretch, and characterise molecular forms of CT-1 in tissue and plasma.. CT-1 levels in human and rat plasma and in rat cardiac tissue extracts were determined by specific radioimmunoassay (RIA). Cardiac CT-1 secretion during ventricular stretch was studied in isolated, perfused hearts. Molecular forms of CT-1 were identified using RIA coupled with high performance liquid chromatography (HPLC). Results are given as mean+/-SEM.. Plasma levels of CT-1 in patients with untreated hypertension (UTH, 606+/-18 pmol/L, n=24) were significantly higher than those in age-and BMI-matched normotensive volunteers (NT, 546+/-12 pmol/L, n=31, P<0.01 vs. UTH). CT-1 levels in matched patients with treated hypertension (THT, 618+/-10 pmol/L, n=35) were similar to those in UTH patients, but higher than in NT controls (P<0.01). Plasma CT-1 demonstrated a weak but significant correlation with systolic blood pressure in all patients (r=0.241, P<0.05, n=90). In contrast, CT-1 levels in male, 40-week-old, NT-WKY rats (1295+/-98 pmol/L) were significantly higher than those in matched UTH-SHR (937+/-31 pmol/L, P<0.01). In both WKY and SHR rats, atrial tissue concentrations of CT-1 were 8-fold higher than ventricular levels. Left ventricular tissue CT-1 protein concentrations were significantly higher in 40-week-old SHR compared with age-matched WKY (SHR 12.6+/-0.5 fmol/g vs. WKY 9.5+/-0.8 fmol/g, P<0.01). Ventricular stretch of Langendorff perfused, isolated WKY/SHR hearts resulted in significant, acute release of CT-1 and BNP. HPLC coupled with specific RIA revealed CT-1 in human/rat plasma, isolated rat heart perfusate, and rat heart tissue extracts to consist of complex, high molecular weight forms.. This is the first report to show increased levels of plasma CT-1 in hypertensive disease. CT-1 is a unique cardiac cytokine whose release is stimulated by ventricular stretch. The atrium contains the highest levels of the protein. The stored and circulating molecular form of CT-1 is complex, which may modulate its in vivo role in cardiovascular disease.

Topics: Aged; Animals; Case-Control Studies; Chromatography, High Pressure Liquid; Cytokines; Female; Heart; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Perfusion; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stress, Mechanical

Transfusion-associated circulatory overload (TACO) occurs when the transfusion rate or volume exceeds the capacity of a compromised cardiovascular system. Characteristic symptoms and signs associated with TACO are neither sensitive nor specific. B-natriuretic peptide (BNP) is a 32-amino-acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. This study was performed to explore the usage of BNP in the differential diagnosis of TACO.. Pre- and posttransfusion BNP levels were determined in 21 patients with suspected TACO and 19 control patients. The BNP was considered significant if the posttransfusion-to-pretransfusion ratio was at least 1.5 and the posttransfusion BNP level was at least 100 pg per mL.. The BNP test has a sensitivity and specificity of 81 and 89 percent, respectively, in diagnosis of TACO. It has a positive predictive value of 89 percent, a negative predictive value of 81 percent, and an accuracy of 87 percent. In logistic regression analysis, BNP was found to have significant predictive power independent of other clinical variables in models predicting which patients had TACO.. Our study suggests that in patients who present symptoms suggestive of TACO, BNP can be a useful adjunct marker in confirming volume overload as the cause of acute dyspnea and symptoms related to cardiovascular compromise.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Diagnosis, Differential; Dyspnea; Female; Heart Failure; Humans; Hypertension; Immunoassay; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Respiratory Distress Syndrome; Risk Factors; Sensitivity and Specificity; Tachycardia; Transfusion Reaction

Obesity is associated with lower B-type natriuretic peptide (BNP) levels in healthy individuals and patients with chronic congestive heart failure (CHF). Neither the mechanism of natriuretic peptide suppression in the obese patient nor whether obesity affects natriuretic peptide levels among patients with acute CHF is known.. The associations of amino-terminal pro-BNP (NT-proBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute CHF. Multivariable regression analyses were performed to identify factors independently related to NT-proBNP and BNP levels.. Across clinical strata of normal (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2) patients, median NT-proBNP and BNP levels decreased with increasing BMI (both P values < .001). In multivariable analyses adjusting for covariates known to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and BNP remained ( P < .05 for both). Using a cut point of 900 pg/mL, NT-proBNP was falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m2) and 15% in obese patients (> or =30 kg/m2). Using the standard cut point of 100 pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight and obese patients. The assays for NT-proBNP and BNP exhibited similar overall sensitivity for the diagnosis of CHF.. When adjusted for relevant covariates, compared with normal counterparts, overweight and obese patients with acute CHF have lower circulating NT-proBNP and BNP levels, suggesting a BMI-related defect in natriuretic peptide secretion. NT-proBNP fell below the diagnostic cutoff for CHF less often than BNP in overweight and obese individuals; however, when used as a diagnostic tool to identify CHF in such patients, both markers may have reduced sensitivity.

Topics: Acute Disease; Aged; Biomarkers; Body Mass Index; Comorbidity; Creatinine; Diabetes Complications; Dyspnea; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Sensitivity and Specificity; Troponin T

This study investigates whether the plasma brain natriuretic peptide (BNP) level is increased by the clinical traits of diabetes, including its complications, and whether these levels are affected by the presence of other combined diseases such as hypertension, hyperlipidemia, and coronary heart disease (CHD) in patients with diabetes. In 223 patients with Type 2 diabetes, the mean value of plasma BNP reached 32.3+/-4.1 pg/mL. The levels significantly increased with age, hypertension, and CHD but not with the duration of diabetes, HbA1c level, or hyperlipidemia. With regard to the type of therapy, the BNP levels were significantly lower in the combinations of both sulfonylurea and metformin and sulfonylurea and pioglitazone than those in insulin alone. In addition, the BNP levels in the group with diabetic complications, including retinopathy and nephropathy, and macroalbuminuria were significantly elevated in comparison with those without these complications and macroalbuminuria. Interestingly, however, no difference was observed between these groups after removal of the values in patients with CHD. These results have clarified that the plasma BNP levels in diabetic patients could increase only by the progression of macrovascular diseases, such as CHD, but not by the current diabetic control or diabetic microvascular complications.

Topics: Age Factors; Aged; Aged, 80 and over; Albuminuria; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Natriuretic Peptide, Brain

Recently there has been a growing interest in risk assessment of individuals, using biochemical markers of cardiac risk, with an increasing focus on a multi-marker strategy. Natriuretic peptides (BNP and NT-proBNP) are well-established markers of increased risk in the general population and in high-risk groups with hypertension, and coronary heart disease. However, there is at present no indication for routine measurements of natriuretic peptides in the risk assessment of individuals or patients, as there is no evidence for subsequent therapeutic initiatives. Natriuretic peptides are useful when screening for heart failure in symptomatic individuals. However, the use of NT-proBNP screening for risk or left ventricular systolic dysfunction in the general population is still a matter of debate.

Topics: Biomarkers; Coronary Disease; Humans; Hypertension; Natriuretic Peptide, Brain; Peptide Fragments; Risk

We wanted to investigate the relationship of N-terminal pro brain natriuretic peptide (Nt-proBNP) to metabolic and hemodynamic cardiovascular (CV) risk factors in the general population. From a population-based sample of 2656 people 41, 51, 61, or 71 years of age, we selected 2070 patients without previous stroke or myocardial infarction who did not receive any CV, antidiabetic, or lipid-lowering treatment in 1993 to 1994. Traditional CV risk factors, 24-hour blood pressures, left ventricular (LV) mass, and ejection fraction by echocardiography, pulse wave velocity, urine albumin/creatinine ratio (UACR), and serum Nt-proBNP were measured in 1993 to 1994. The metabolic syndrome was defined in accordance with the definition of the European Group for the Study of Insulin Resistance (EGIR). Higher log(Nt-proBNP) was in multiple regression analysis related to female gender (beta=-0.37), older age (beta=0.32), higher clinic pulse pressure (beta=0.20), lower serum total cholesterol (beta=-0.15), lower LVEF (beta=-0.08, all P<0.001), lower log(serum insulin) (beta=-0.07), lower log(plasma glucose) (beta=-0.06, both P<0.01, lower log(serum triglyceride) (beta=-0.06), lower body mass index (beta=-0.05); lower heart rate (beta=-0.05), higher logUACR (beta=0.04, all P<0.05) and higher log(LV mass index) (beta=0.04, P=0.07), adjusted R2=0.35, P<0.001). The metabolic syndrome was associated with lower Nt-proBNP (35 pg/mL versus 48 pg/mL; P<0.001) and shifted the positive relationship between pulse pressure and Nt-proBNP to the right (ie, higher blood pressure for a given level of Nt-proBNP). The metabolic syndrome was associated with lower Nt-proBNP levels and shifted the positive relationship between Nt-proBNP and pulse pressure to the right, creating a possible link between the metabolic syndrome and hypertension.

Topics: Adult; Aging; Blood Pressure; Cardiovascular Diseases; Dyslipidemias; Echocardiography; Female; Humans; Hyperinsulinism; Hypertension; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Risk Factors; Sex Factors; Stroke Volume

The aim of the present study was to prospectively evaluate the diagnostic utility of B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) measurements for the detection of cardiac structural disease in asymptomatic patients with systemic arterial hypertension and to test the hypothesis that the 2 analytes are equally useful in this clinical setting.. We studied a consecutive series of 149 asymptomatic patients referred for echocardiographic evaluation of the cardiac effects of systemic arterial hypertension. Diagnosis of cardiac structural disease was based on the presence of systolic or diastolic dysfunction, left atrial dilatation, left ventricular dilatation or hypertrophy, pulmonary hypertension, and wall motion or valvular abnormalities. Blood concentrations of BNP and NT-proBNP were measured by 2 commercially available assays (Abbott AxSYM and Roche Elecsys, respectively). Diagnostic accuracies of BNP and NT-proBNP were assessed by ROC curve analysis. Areas under the curves were compared by analysis of equivalency.. In distinguishing between hypertensive patients with cardiac structural disease (n = 118) and hypertensive patients without (n = 31), areas under the curves were 0.740 (95% confidence interval, 0.662-0.808) for BNP and 0.762 (0.685-0.828) for NT-proBNP and were significantly equivalent (P = 0.015). Cutoff values with a 90% sensitivity for cardiac structural disease were 17 ng/L for BNP and 39 ng/L for NT-proBNP, with 29% and 32% specificity, respectively.. BNP and NT-proBNP have similar capabilities for detecting cardiac structural disease in asymptomatic patients with systemic arterial hypertension. However, in the setting evaluated, a screening strategy relying on measurement of BNP or NT-proBNP may be of limited value because of the low specificity at the selected cutoff values.

Topics: Aged; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Protein Precursors; Sensitivity and Specificity

The accuracy of the tissue Doppler E/Ea and color M-mode Doppler E/Vp indexes in diagnosing congestive heart failure (HF) was investigated in 20 chronic hypertensive patients with acute dyspnea and normal left ventricular ejection fractions who met Vasan's criteria for definite diastolic HF, compared with 20 gender- and age-matched hypertensive patients with noncardiac cause of acute dyspnea. The E/Ea ratio appeared to be more reproducible (variability 4% to 9% vs 6 to 14%) and more precise (sensitivity 77.8%, specificity 100%, and accuracy 89.5% for the optimal cutoff of 11 vs sensitivity 73.7%, specificity 75%, and accuracy 74.3% for the optimal cutoff of 1.5) than the E/Vp ratio in this clinical setting.

Topics: Aged; Aged, 80 and over; Blood Flow Velocity; Chronic Disease; Coronary Angiography; Coronary Artery Disease; Echocardiography; Echocardiography, Doppler, Color; Emergency Medical Services; Female; Heart Failure; Humans; Hypertension; Male; Mitral Valve; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Stroke Volume; Ventricular Function, Left

The mechanisms linking obesity to hypertension have not been established, but sodium retention and excessive sympathetic tone are key contributors. The natriuretic peptides are important regulators of sodium homeostasis and neurohormonal activation, raising the possibility that obese individuals have an impaired natriuretic peptide response.. We examined the relations of plasma B-type natriuretic peptide (BNP) and N-terminal proatrial natriuretic peptide (N-ANP) to body mass index in 3389 Framingham Study participants (1803 women) without heart failure. Multivariable regression analyses were performed, adjusting for clinical and echocardiographic covariates. BNP levels below the assay detection limit and N-ANP levels in the lowest sex-specific quartile were categorized as low. Multivariable-adjusted mean plasma BNP levels in lean (<25 kg/m2), overweight (25 to 29.9 kg/m2), and obese (> or =30 kg/m2) men were 21.4, 15.5, and 12.7 pg/mL, respectively (trend P<0.0001). Corresponding values in women were 21.1, 16.3, and 13.1 pg/mL (trend P<0.001). A similar pattern was noted for plasma N-ANP. Obese individuals had higher odds of having low plasma BNP (multivariable-adjusted odds ratios: men, 2.51; 95% CI, 1.71 to 3.68; women, 1.84; 95% CI, 1.32 to 2.58) and low plasma N-ANP (odds ratios: men, 4.81; 95% CI, 2.98 to 7.76; women, 2.85; 95% CI, 2.01 to 4.04) compared with lean individuals. Diabetes also was associated with low plasma natriuretic peptide levels, and the negative effects of obesity and diabetes on natriuretic peptide levels were additive.. Obese individuals have low circulating natriuretic peptide levels, which may contribute to their susceptibility to hypertension and hypertension-related disorders.

Topics: Atrial Natriuretic Factor; Body Constitution; Body Mass Index; Diabetes Complications; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Protein Precursors

In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass index (R=0.47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy and preserved LV function demonstrated that NT-proBNP was a very strong prognostic marker, especially combined with a history of cardiovascular disease. Patients with high NT-proBNP and known cardiovascular disease had a seven-fold increase in CV events compared to patients with low NT-proBNP and no CV disease, while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk stratification and perhaps monitoring of treatment in patients with arterial hypertension.

Topics: Aged; Aged, 80 and over; Biomarkers; Body Weights and Measures; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Ventricular Function, Left

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antihypertensive Agents; Biomarkers; Blood Pressure Determination; Cardiomyopathy, Hypertrophic; Combined Modality Therapy; Home Nursing; Humans; Hypertension; Immunoglobulin Fab Fragments; Myocardial Infarction; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Recombinant Proteins; Tissue Plasminogen Activator

We investigated whether inappropriately high left ventricular (LV) mass, defined as observed LV mass exceeding the level of individual LV mass predicted from gender, height, and stroke work, may be associated with an imbalance between growth-promoting and growth-inhibitory factors and/or structural vascular changes. In 53 patients with hypertension and electrocardiographic LV hypertrophy, 24-h ambulatory blood pressure (BP); echocardiographic LV mass, stroke volume and stroke work; minimal forearm vascular resistance (MFVR); and intima-media cross-sectional area in common carotid arteries (IMA) were evaluated after 2 weeks of placebo treatment. Serum insulin, plasma epinephrine, norepinephrine, endothelin, angiotensin II, aldosterone, and brain natriuretic peptide (BNP) were also measured. High observed LV mass was related to high IMA (r=0.46, P<0.001), MFVR (in men: r=0.36, P<0.05), 24-h ambulatory systolic BP (r=0.30, P=0.06), and lower plasma angiotensin II (r=-0.33, P<0.05), but not to other circulating growth factors. Stroke work was similarly related to IMA (r=0.42, P<0.01), MFVR (in men: r=0.41, P<0.05), and plasma angiotensin II (r=-0.32, P<0.05). Inappropriate LV mass, identified by the ratio between observed LV mass and the value predicted for gender, height, and stroke work, was not significantly related to any of the arterial or neurohormonal variables. In this small series of older hypertensive patients, inappropriate LV mass was not significantly related to arterial changes or to measured circulating growth factors, although weak relations cannot be excluded. Alternatively, inappropriately high LV mass might be related to unmeasured factors such as local myocardial alterations in growth factors and/or genetic predisposition to develop excessive LV hypertrophy.

Topics: Aged; Carotid Arteries; Female; Growth Substances; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Tunica Intima; Tunica Media; Ultrasonography; Vascular Resistance

From a previous survey of cardiac nurses attending a scientific conference, we learned that these nurses adopted a healthier lifestyle than the general population.. The aim of this study was to determine the overall profile of cardiac risk factors in a similar cohort and determine whether cardiac nurses continue to 'practice what they preach' in this regard. Secondly, we examined the practical value of screening a large cohort of individuals within a short time frame (total of 8 hours screening time) and determined the range of BNP concentrations within a 'healthy' cohort.. Data on CHD risk factors were collected with a short self-report questionnaire. The sample consisted of 122 cardiac nurses from 19 countries attending a European cardiac nursing conference held in Stockholm. A venous blood sample was collected into a tube containing potassium ETDA. B-type natriuretic peptide was measured on-site with the use of a portable fluorescence immunoassay kit.. Most participants were female (89%). Participants ranged in age from 23 to 60 years with a mean age of 41 (S.D. 9.4). Eleven percent - all female - reported they were current smokers, 27% (34) had a BMI >25 and 27% of the sample stated they did not exercise regularly. Almost half (48%) of the sample reported a family history of CHD. As expected, all BNP-values were within the normal range. There were significant differences in BNP on the basis of sex (P<0.05) and age (P<0.05) and a trend towards increasing BNP concentrations with progressively higher BMI scores (P=0.06).. This study reconfirms the likelihood that many cardiac nurses heed their own advice on lifestyle modification to reduce cardiovascular risk and therefore provide a good role model for the promotion of primary and secondary prevention initiatives.

Topics: Adult; Attitude to Health; Cardiology; Coronary Disease; Diabetes Complications; Europe; Female; Fluorescence Polarization Immunoassay; Health Behavior; Health Knowledge, Attitudes, Practice; Health Surveys; Humans; Hypertension; Life Style; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Nurse Clinicians; Obesity; Risk Assessment; Risk Factors

Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD.. Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM.. The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Coronary Vessels; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Pressure; Ventricular Dysfunction, Left; Ventricular Function

Greater change of postural blood pressure (BP) is often seen in elderly hypertensives and is recognized as a risk factor for cognitive decline and poorer cerebrovascular outcome, but its clinical significance still remains to be clarified. We performed a head-up tilting test, ambulatory BP monitoring, and brain MRI in 59 hypertensives and 27 normotensive subjects. We measured plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels at rest to assess cardiac burden. The 59 hypertensive patients were classified into 3 groups: an orthostatic hypertension (OHT) group with orthostatic increase in systolic BP (SBP) > or = 10 mmHg (n=16); an orthostatic hypotension (OHYPO) group with orthostatic SBP decrease < or = -10 mmHg (n=18); and an orthostatic normotension (ONT) group with neither of these two patterns (n=25). A group of 27 normotensive subjects (NT) was also included as a control. Plasma BNP (72 +/- 92 vs. 29 +/- 24 pg/ml, p < 0.05) and BNP/ANP ratio (4.6 +/- 3.3 vs. 2.4 +/- 1.5, p < 0.05) were significantly higher in the OHYPO than in the NT group. The BNP/ANP ratio was also higher in the OHT than in the NT group (5.1 +/- 3.9 vs. 2.4 +/- 1.5, p < 0.01). The number of silent cerebral infarct (SCI), prevalence of SCI and number of multiple SCIs was the highest in the OHT group, followed in order by the OHYPO, ONT and NT groups. Blood pressure and left ventricular mass index were not significantly different among the 3 hypertensive groups. In conclusion, hypertensive patients with greater change of postural BP (OHT and OHYPO) were shown to have increased risk of advanced silent brain lesions and greater cardiac burden.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Cerebral Infarction; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypotension, Orthostatic; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.. We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography.. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values.. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Female; Heart Diseases; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Ventricular Dysfunction, Left; Ventricular Function, Left

Plasma brain natriuretic peptide (BNP) was evaluated before and after sinus rhythm restoration in patients with paroxysmal and persistent atrial fibrillation (AF) who had underlying hypertension or coronary heart disease and normal left ventricle function. Twenty-four hours after successful cardioversion, plasma BNP decreased significantly to levels that had been measured in controlled subjects: from 95 to 28 pg/ml in 24 patients in the paroxysmal AF group and from 75 to 41 pg/ml in 36 patients in the persistent AF group. This indicates that AF affects BNP secretion in patients with AF and that some BNP may be atrially delivered.

Topics: Atrial Fibrillation; Case-Control Studies; Coronary Disease; Electric Countershock; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

It has been published that hypertension (HT) must be taken into account when using NT-proBNP, but left ventricular (LV) hypertrophy without HT could be a cause of NT-proBNP elevation. In a population study we compared NT-proBNP in subjects with hypertrophy, with and without diagnosis of HT.. We studied 215 subjects from a random sample of 432 people who had declared to suffer from dyspnea. These 432 subjects were referred to their hospital where blood samples were taken, an echo-Doppler study was performed and a specific questionnaire was completed. We got a positive answer from 215, and 52 (24%) have LV hypertrophy.. When we compared NT-proBNP in non-hypertrophic population, 148 +/- 286 pg/ml, with NT-proBNP in LV hypertrophic population, 202 +/- 209 pg/ml, we found P < 0.001. In the hypertrophic group, when we compared NT-proBNP (199 +/- 201 pg/ml) in normotensive subjects (LV mass index 170 +/- 70 g/m2, Vp 50 +/- 18 cm/s, LVEF 62 +/- 8) with NT-proBNP (205 +/- 220 pg/ml) in subjects with diagnosis of HT (LV mass index 169 +/- 37 g/m2, Vp 55 +/- 20 cm/s, LVEF 64 +/- 10), we found NS.. This population study shows that NT-proBNP is elevated in patients with LV hypertrophy with or without HT. In LV hypertrophy the presence of HT does not influence the peptide levels significantly.

Topics: Aged; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Echocardiography, Doppler; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Observer Variation; Peptide Fragments; Probability; Prognosis; Reference Values; Reproducibility of Results; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric

Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF.. Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (Sa) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios.. Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/ 90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 +/- 57 to 74 +/- 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise Sa, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027).. Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.

Topics: Atrial Function, Left; Diastole; Dyspnea; Echocardiography; Exercise; Exercise Tolerance; Heart Failure; Hemodynamics; Humans; Hypertension; Natriuretic Peptide, Brain; ROC Curve; Stroke Volume; Ventricular Function, Left

Topics: Antihypertensive Agents; Atrial Natriuretic Factor; Blood Volume; Cohort Studies; Cross-Sectional Studies; Diet, Reducing; Disease Susceptibility; Humans; Hypertension; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Thinness

The prevalence of inflammation is high among patients with chronic renal failure but the reason of inflammation is unclear. We test the hypothesis that inflammation in chronic renal failure could be the consequence of an increased left-ventricular wall tension related to ventricular dysfunction, hypervolemia or both.. For assessing left-ventricular filling pressure, plasma level of N-terminal pro-B-type natriuretic peptide (N-BNP) was used, as B-type natriuretic peptide is secreted from the cardiac ventricles in response to increased wall tension. N-BNP levels and C-reactive protein (CRP) were measured on the same day in 75 pre-dialysis patients. A previous history of cardiomiopathy with systolic dysfunction was present in 27 (36%) of them.. The levels of N-BNP were not normally distributed (mean: 2,589 +/- 4,514 pg/ml; median: 789 pg/ml). The distribution of CRP levels was also not normal (mean: 15 +/- 27 mg/l; median: 5 mg/l). Both parameters correlated significantly (r: 0.41; p < 0.005). N-BNP was higher (p < 0.001) in patients with known ventricular dysfunction. Excluding these patients, the correlation between N-BNP and CRP was stronger (r: 0.88; p < 0.001). Univariate analysis in these patients without known cardiomyopathy showed that N-BNP levels also correlated with systolic and diastolic blood pressure (r: 0.54; p < 0.005) and inversely with creatinine clearance (r: -0.43; p < 0.01), serum albumin (r: 0.6; p < 0.001) and hemoglobin levels (r: 0.37; p < 0.05). CRP levels correlated significantly (p < 0.01) with the same parameters as N-BNP in univariate analysis. However, in multiple stepwise regression analysis in which CRP was the dependent variable, only the association with N-BNP remained significant (r: 0.87; p < 0.001).. Our results suggest a link between left-ventricular filling pressure and inflammation in patients with advanced renal insufficiency. The importance of strict volume control in these patients, in order to reduce left-ventricular pressure and therefore inflammation, should be considered.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Coronary Disease; Creatinine; Diabetes Complications; Edema; Female; Ferritins; Heart Ventricles; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Pressure; Serum Albumin; Stroke Volume; Systole; Vasculitis; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is useful for the evaluation of ventricular dysfunction in patients with various cardiac diseases. However, its diagnostic value has been considered to be limited in patients with chronic renal failure (CRF) because renal dysfunction itself may affect BNP levels. This study is designed to clarify the diagnostic and prognostic value of plasma BNP level in patients with CRF.. In 103 non-dialysis-dependent patients with CRF without heart failure and 60 hypertensive patients with normal renal function, echocardiographic examinations and BNP measurements were performed.. Plasma BNP level was much greater in patients with CRF than in hypertensive controls; however, multiple regression analysis showed that left ventricular (LV) end-diastolic volume (EDV) index (LVEDVI) and the difference in mitral and pulmonary venous atrial wave duration (Ad-PVad), a marker of LV end-diastolic pressure, were independent determinants of plasma BNP levels in patients with CRF. The influence of LV overload (LVEDVI > or = 75 mL/m 2 and/or Ad-PVad < 0 milliseconds) on plasma BNP levels in subjects with CRF was independent of the severity of renal dysfunction. From Kaplan-Meier event-free curves (mean follow-up, 13 months), the incidence of heart failure was much greater in patients with a plasma BNP level of 150 pg/mL or greater ( P < 0.001). By means of multivariate Cox regression analysis, high plasma BNP level was the strongest predictor for heart failure events (hazard ratio, 6.31; P < 0.001).. These findings support plasma BNP level as a reliable marker of LV overload, even in nondialysis patients with CRF. Also, a high BNP level (> or =150 pg/mL) may have powerful predictive potential for heart failure in these patients.

Topics: Aged; Female; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Male; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Regression Analysis; Risk Factors; Ventricular Dysfunction, Left

Hypertension is associated with changes in concentrations of vasoactive peptides and procollagen propeptides, but their relationships with left ventricular hypertrophy and cardiac function are unclear.. We measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1), and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and the aminoterminal propeptide of type III procollagen (PIIINP) and echocardiographic parameters in 97 patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial.. Median values (reference values) of the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l, BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2) microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of diastolic dysfunction (1.5 pmol/l) were greater than those in patients without hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05). BNP was the only biochemical parameter that independently predicted interventricular septal diastolic diameter (p<0.05), left ventricular mass index (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the mitral inflow in a stepwise logistic regression analysis (p<0.05).. The results show that BNP reflects the remodelling process in hypertension.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Diastole; Endothelin-1; Humans; Hypertension; Hypertrophy, Left Ventricular; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Protein Precursors; Ultrasonography; Ventricular Dysfunction, Left

Topics: Humans; Hypertension; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Risk Factors

We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure.. In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial.. In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California).. A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011).. In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diastole; Echocardiography; Female; Follow-Up Studies; Heart; Hemodynamics; Humans; Hypertension; Inpatients; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Stress, Mechanical; Stroke Volume; Systole; Ventricular Function, Left

While arterial stiffness is known to be related to atherosclerosis, the association between arterial stiffness and cardiac systolic and diastolic function in hypertension has not been fully evaluated. The present study was conducted to simultaneously evaluate the relationship of brachial-ankle pulse wave velocity (PWV) to parameters reflecting atherosclerosis and to those reflecting the risk of congestive heart failure in patients with hypertension. In 147 patients with hypertension, the left ventricular ejection fraction, the ratio of the peak velocity of early rapid filling and the peak velocity of atrial filling (E/A ratio), and left ventricular mass index were obtained from echocardiographs, the intima-media thickness of the common carotid artery was obtained by ultrasonography, the plasma B-type natriuretic peptide (BNP) level was measured by radioimmunoassay, and the brachial-ankle PWV was measured by the volume rendering method. Brachial-ankle PWV correlated positively with the intima-media thickness of the carotid artery, E/A ratio and BNP. Multiple linear regression analysis demonstrated that the relationship between the brachial-ankle PWV and the E/A ratio was significantly independent from other clinical variables. The receiver operator characteristic curve demonstrated that a brachial-ankle PWV of 1,600 cm/s was useful to discriminate mild cardiac diastolic dysfunction (E/A ratio of < or =0.75) (sensitivity=78% and specificity=58%). The present study demonstrated that increased brachial-ankle PWV relates not only to the parameters reflecting atherosclerosis but also to those reflecting cardiac diastolic dysfunction. Therefore, increased arterial stiffness is a possible simultaneous risk for atherosclerotic cardiovascular disease and diastolic heart failure in patients with hypertension.

Topics: Aged; Ankle; Blood Flow Velocity; Brachial Artery; Carotid Artery Diseases; Diastole; Female; Heart Failure; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Pulsatile Flow; Risk Factors; Systole; Ultrasonography; Ventricular Dysfunction, Left

In spontaneously hypertensive rats a decrease occurs in myocardial energy supply from long-chain triglyceride (LCT) by CD36 gene mutation-induced dysfunction. We investigated whether long-term intake of medium-chain triglyceride, which enters into cells without CD36, upregulates fatty acid metabolic capacity in the heart of spontaneously hypertensive rats, and whether this upregulation improves cardiac hypertrophy and molecular markers. Male 4-week-old spontaneously hypertensive rats were given medium-chain triglyceride (SHR-MCT) or LCT (SHR-LCT) for 16 weeks. After hemodynamic measurement, we determined myocardial fatty acid metabolic enzyme activity and mRNA expression of molecular markers (endothelin-1, alpha-skeletal actin, angiotensin-converting enzyme and brain natriuretic peptide) for cardiac hypertrophy. We used Wistar-Kyoto rats (WKY-MCT and WKY-LCT) as controls. When compared with SHR-LCT rats, SHRMCT rats showed an increase in myocardial fatty acid metabolic enzyme activity and improvement in cardiac function (left ventricular end-diastolic pressure and +dP/dt/P) and cardiac hypertrophy. Blood pressure did not differ between them. The mRNA expression of endothelin-1, alpha-skeletal actin, angiotensin-converting enzyme and brain natriuretic peptide in the heart was significantly higher in SHR-LCT than in WKY-MCT and WKYLCT rats, and there was no significant difference between SHRLCT and SHR-MCT. These findings suggest that medium-chain triglyceride application to spontaneously hypertensive rats improves decreased cardiac function and cardiac hypertrophy without affecting blood pressure and myocardial mRNA expression of molecular markers. Because mechanical stress to the heart is similar between SHR-LCT and SHR-MCT, this may be a reason for the lack of difference in expression of molecular markers.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Actins; Animals; Blood Pressure; Cardiomegaly; Disease Models, Animal; Endothelin-1; Energy Metabolism; Heart Rate; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Time Factors; Triglycerides; Ventricular Function, Left; Ventricular Pressure

Hypertension produced by chronic inhibition of nitric oxide (NO) synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) was used to determine the effect of severe pressure overload with or without left ventricular (LV) hypertrophy on the transcriptional activation of the cardiac fetal genes encoding for the natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), and for beta-myosin heavy chain (MHC) in both atrial and ventricular muscle. A previously reported association of LV hypertrophy with the activation of cardiac renin and angiotensin-converting enzyme (ACE) in this hypertension model was also investigated.. Male Sprague-Dawley rats received L-NAME (75 mg/kg/day) or were left untreated for 4 (n=12) or 8 (n=12) weeks.. L-NAME-treated rats became severely hypertensive in both treatment groups but only five out of 12 8-week treatment animals showed a significantly increased LV weight to body weight (BW) ratio (LVW/BW). LV ANF mRNA, but not LV BNP mRNA, correlated significantly with LVW/BW only in animals showing LV hypertrophy. No changes were observed in atrial gene expression or plasma concentration of ANF or BNP. A significant correlation was found between LVW/BW and LV renin mRNA and LV ACE activity in rats with LV hypertrophy. LV beta-MHC mRNA levels were significantly increased in the LV of rats with or without LV hypertrophy at both 4 and 8 weeks of treatment.. It is concluded that pressure overload per se does not promote NP or cardiac renin-angiotensin system gene expression while increased beta-MHC expression is a marker of LV pressure overload even in the absence of LV hypertrophy. It is apparent that L-NAME causes a disruption in the coordinated transcriptional activation of cardiac fetal genes expected of hypertrophic stimuli acting on the LV.

Topics: Animals; Atrial Natriuretic Factor; Enzyme Inhibitors; Gene Expression Regulation; Heart Ventricles; Hypertension; Male; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger

Increased brain natriuretic peptide (BNP) expression in the ventricles antedates elevated blood pressure (BP) in experimental studies. We hypothesized that higher plasma BNP levels in nonhypertensive individuals may be associated with a greater likelihood of future BP increase and/or hypertension. We evaluated the relations of plasma BNP to longitudinal BP tracking and incidence of hypertension in 1801 nonhypertensive Framingham Heart Study participants (mean age, 56 years; 57% women) by using gender-specific multivariable logistic regression. Progression of BP stage was defined as an increment of one or more BP categories, as classified by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Hypertension was defined as a systolic BP > or =140 or diastolic BP > or =90 mm Hg or use of antihypertensive medications. On follow-up 4 years from baseline, progression of BP category was observed in 36.2% of men and 33.1% of women; hypertension developed in 16.4% of men and 15.5% of women. In multivariable models adjusting for known risk factors, elevated plasma BNP level was associated with increased risk of BP progression in men (odds ratio of 1.15 for trend across categories, P=0.046) but not in women (P=0.82). There were no significant trends of increasing incidence of hypertension across BNP categories in men or women. In our community-based sample, higher plasma BNP levels were associated with increased risk of BP progression in men but not women. Additional investigations are warranted to confirm these findings and elucidate the basis for these gender-related differences.

Topics: Blood Pressure; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Sex Factors

Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the role of mechanical load in regulating gene expression of AM by using two hypertensive rat strains as experimental models. Acute pressure overload was produced by arginine(8)-vasopressin (AVP, 0.05 microg/kg/min, i.v.) infusion in conscious spontaneously hypertensive rats (SHR) and double transgenic rats (dTGR) harboring both the human renin and angiotensinogen genes and in their respective normotensive strains. A significant increase in left ventricular AM mRNA levels was seen in the left ventricles of all rat strains, the increase being augmented in hypertensive strains. Direct left ventricular wall stretch in isolated, perfused rat heart preparation also activated AM gene expression. However, stretching of cultured neonatal ventricular myocytes resulted in inhibition of AM gene expression, and stretch also blocked hypoxia-induced increase in AM gene expression. The present study shows that cardiac AM gene expression is upregulated in response to pressure overload and that this upregulation may be mediated via cell types other than cardiac myocytes.

Topics: Adrenomedullin; Animals; Arginine Vasopressin; Gene Expression Regulation; Heart Ventricles; Humans; Hypertension; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptides; Pressure; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; RNA, Messenger

Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction.. BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.. The 91 patients with no-CIE with echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (63 +/- 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 +/- 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 +/- 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 +/- 60 pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).. BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.

Topics: Atrial Fibrillation; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left

To assess the accuracy of B-type natriuretic peptide (BNP) plasma levels for the diagnosis of left ventricular hypertrophy (LVH) in hypertensive patients.. We studied a sample of 409 adults aged 45 years or older, recruited from residents of Porto by random digit dialing. Data were collected by clinical interview and physical examination, ECG, echocardiogram and venous blood sampling for the measurement of plasma concentrations of BNP. Hypertension (HT) was defined as blood pressure > or = 140/90 mmHg on the day of interview and/or self-reported HT if treated with any antihypertensive medication; LVH was defined as left ventricular mass index (LVMI) > or = 125 g/m2 in men and 110 g/m2 in women. The participants were further classified in four strata according to left ventricular morphology--normal, concentric remodeling, eccentric LVH or concentric LVH.. Two hundred and thirty-two (56.7%) individuals were hypertensive, and among these 73 (31.5%) had LVH. BNP levels were significantly higher in these individuals (median [P25-P75] = 55.8 pg/ml [22.6-88.4]) than in hypertensive patients without LVH (29.9 pg/ml [10.0-62.8]), p = 0.003. BNP levels also differed significantly across strata of left ventricular geometry, the main difference depending on the presence or absence of LVH. There was a positive correlation between plasma BNP levels and LVMI (Spearman's P 0.185, p = 0.005). The area under the ROC curve--a parameter for diagnostic accuracy quantification--was 0.62 (95% confidence interval 0.54-0.70), indicating low discriminatory power between normal and abnormal LVMI.. In the assessed population, BNP levels were higher in hypertensive patients with LVH than in the absence of LVH. However, BNP did not perform well in discriminating between the presence or absence of LVH.

Topics: Aged; Atrial Natriuretic Factor; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain

Proinflammatory cytokines are capable of modulating cardiovascular function by a various mechanisms. The aim of the study was to evaluate the influence of the selected cytokines: tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (L-6), endothelin 1 (ET-1) on the remodeling of the heart in patients with congestive heart failure (1-year follow-up). The study was made in 45 patients with congestive heart failure treated in the Department of Cardiology. Of these, 31 were men aged from 44 to 77 and 14 were women aged from 48 to 79. Ischaemic heart disease was diagnosed in 22 patients and ischaemic heart disease and hypertension in 10 patients, dilated cardiomyopathy was diagnosed in 6 patients and postinflammatory cardiomyopathy in 7 patients. Blood samples for determination of TNF-alpha, IL-1, IL-2, IL-6, ET-1, aldosterone, catecholamines, brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels were obtained prior to the treatment and in 3 and 6 and 12 month follow-up. At the same time were estimated: NYHA functional class, structure, systolic and diastolic left ventricle function of the heart using echocardiography and 24-hour ECG Holter monitoring (HR, supraventricular and ventricular arrhythmias). TNF-alpha, IL-1, IL-2, IL-6, ET-1, aldosterone, catecholamines, BNP and ANP plasma levels were determined with radioimmunological assay. In patients with progression of congestive heart failure (worsening of NYHA class and ejection fraction of left ventricle) the plasma concentrations of TNF-alpha and ET-1 significantly increased in following observations. In this group patients we determined a correlation between ejection fraction of the left ventricle and serum concentration of TNF-alpha and ET-1. In patients with improving of NYHA functional class and ejection fraction of left ventricle the plasma concentrations of cytokines were not altering. In all patients the plasma concentration of TNF-alpha correlated with ANP and BNP concentrations.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Catecholamines; Cytokines; Echocardiography; Endothelin-1; Female; Follow-Up Studies; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Interleukin-1; Interleukin-2; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Radioimmunoprecipitation Assay; Severity of Illness Index; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Remodeling

To evaluate the relationship between the left ventricular diastolic function and plasma level of plasma brain natriuretic peptide (BNP) among patients with pregnancy-induced hypertension (PIH) syndrome.. The left ventricular diastolic function was evaluated by Doppler echocardiography, and plasma BNP level was tested by radioimmunoassay among 36 pregnant women with severe PIH, 32 normal pregnant women, and 21 normal non-pregnant women of childbearing age.. The parameters such as peak mitral flow velocity in early diastole (E), E-wave velocity-time integral (EVTI), the ratio of peak mitral flow velocity in early diastole and peak A-wave velocity in late diastole (E/A), peak pulmonary venous diastolic forward flow velocity (D) and D-wave velocity-time integral (DVTI) of the 36 severe PIH patients were significantly lower than those of the 32 normal pregnant women and those of the 21 normal non-pregnant women of child-bearing age. But the parameters such as A, A-wave velocity integral (AVTI), and peak pulmonary venous diastolic forward flow velocity (AR) were significantly higher than those of the normal pregnant women and those of the normal non-pregnant women of child-bearing age. E/A ratio, D and DVTI of the normal pregnant women were significantly lower than those of the normal non-pregnant women of child-bearing age, however, A, AVTI, S/D, and AR were significantly higher than those of the normal non-pregnant women of child-bearing age. The BNP concentration of the normal pregnant women was significantly higher than that of the normal non-pregnant women of childbearing age, but significantly lower than that of the severe PIH patients. There were significant correlations between left ventricular diastolic function variables (E/A ratio and AR) and BNP concentration in normal pregnant women and in PIH patients.. The left ventricular diastolic function is slightly damaged in normal pregnant women and significantly damaged in patients with severe PIH. The plasma BNP level of pregnant women can become an excellent index to predict their left ventricular diastolic function.

Topics: Adult; Diastole; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Ventricular Function, Left

Left ventricular hypertrophy, in particular concentric, accompanying hypertension is an independent risk factor of sudden death and other serious cardiovascular complications. It is still not clear how ANP and BNP are related to various types of left ventricular geometry and whether BNP is a better predictor of left ventricular hypertrophy and dysfunction than ANP. The aim of the study was estimation of plasma ANP and BNP levels in patients with hypertension in relation to the changes of left ventricular geometry. Investigations were carried out in 80 patients aged 52.5 +/- 12.6. In every patient plasma levels of ANP and BNP were estimated, blood pressure was measured and echocardiographic study was performed. Based on echocardiographic measurements every patient was classified into one of four left ventricular geometric patterns. It was found that in patients with left ventricular concentric hypertrophy plasma level of ANP and BNP was increased whereas in patients with concentric remodeling and eccentric hypertrophy only plasma level of ANP was elevated. In patients with concentric hypertrophy higher levels of ANP and BNP were found compared to patients with concentric remodeling and eccentric hypertrophy.

Topics: Atrial Natriuretic Factor; Electrocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain

The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in cardiac pressure overload.. Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours. Ang II-induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal alpha-actin and beta-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II-induced hypertension. In parallel, Ang II-stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression of vascular endothelial growth factor and fibroblast growth factor-1 was downregulated by Ang II only in the presence of AT2-R blockade.. Our results provide evidence that AT2-R plays a functional role in the cardiac hypertrophic process in vivo by selectively regulating the expression of growth-promoting and growth-inhibiting factors.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin II Type 2 Receptor Blockers; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Hypertrophic; Fibroblast Growth Factor 1; Gene Expression Regulation; Genes, fos; Heart Rate; Hypertension; Imidazoles; Infusion Pumps, Implantable; Losartan; Male; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-fos; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 2; RNA, Messenger; Vascular Endothelial Growth Factor A

In hypertensive patients, diminished nocturnal blood pressure (BP) fall is associated with poor prognosis for cardiovascular events. However, the relation of insulin resistance with the etiology of nondipper essential hypertension remains unclear. The aim of the present study was to assess the role of insulin resistance in diminished nocturnal BP fall, left ventricular hypertrophy (LVH), and increased plasma atrial (ANP) and brain natriuretic peptides (BNP) in essential hypertensive patients. One hundred and three patients with essential hypertension were divided into dippers (n = 57; age: 57 +/- 5 years, mean +/- SD) or age-matched nondippers (n = 46; 57 +/- 4 years), based on ambulatory BP (ABP) monitoring. Although the systolic and diastolic ABP values were similar during the day, those at night were higher in nondippers than in dippers ( p < 0.0001 for each). Echocardiographic findings revealed that the left ventricular mass index (LVMI) was higher in nondippers (p < 0.0001). Plasma ANP and BNP were also higher in nondippers (p < 0.0001 for each). Fasting plasma concentrations of glucose and insulin (p < 0.0001 for each) and the homeostasis model assessment (HOMA) index (p < 0.0001) were also higher in nondippers. Multivariate analysis revealed that systolic ABP at night was a significant factor for LVMI, ANP and BNP. In addition, the HOMA index was a significant factor for LVMI and BNP. These observations suggest that diminished nocturnal BP fall is closely related to the development of LVH with concomitant increase in BNP in essential hypertensive patients, and that insulin resistance may play a key role in these processes.

Topics: Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Circadian Rhythm; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain

Several reports have suggested that plasma B-type natriuretic peptide (BNP) levels are elevated in hypertensive patients especially with left ventricular (LV) hypertrophy. However, few data have been available concerning the utility of plasma BNP measurement to identify LV hypertrophy in hypertensive patients in a general population screening context.. We measured plasma BNP concentrations in 1112 volunteers in a health screening program (mean age, 57 years). All subjects underwent electrocardiography, chest X-ray, and echocardiography. Among the sample, 284 subjects were designated as hypertensive because they were on antihypertensive drugs or showed elevated systemic blood pressure. By echocardiography, 36 of the hypertensive patients showed significant LV hypertrophy.. There were no significant differences in age and sex between the LV hypertrophy and non-LV hypertrophy groups. Plasma BNP levels in the LV hypertrophy group were significantly higher than in the non-LV hypertrophy group (19.4 +/- 18.9 v 28.2 +/- 28.2 pg/mL; P <.05). However, the ability of plasma BNP levels to discriminate between LV hypertrophy and non-LV hypertrophy patients was not sufficient as the area under the receiver operating characteristic curve was 0.588 (95% CI: 0.528-0.646) with sensitivity of 50.0% and specificity of 69.0%. Positive and negative predictive values for detecting LV hypertrophy among hypertensive patients were 18.9% and 90.5%, respectively. This ability did not improve significantly when the screening was limited to patients with untreated LV hypertrophy or concentric LV hypertrophy.. Plasma BNP testing in a mass screening setting is of limited use for the identification of LV hypertrophy patients among hypertensive patients with heterogeneous etiology.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity

B-type natriuretic peptide (BNP) levels increase in systolic heart failure (HF). However, the value of BNP in hypertensive patients with suspected diastolic HF (symptoms suggestive of HF but normal ejection fraction) and its relation to myocardial function in these patients is unclear. We prospectively studied 72 ambulatory hypertensive subjects (40 women, mean age 58 +/- 8 years) with exertional dyspnea and ejection fraction > or =50%. Diastolic function was evaluated with transmitral and pulmonary venous Doppler, mitral annular velocities (pulsed-wave tissue Doppler), and flow propagation velocity (color M-mode). Systolic function was assessed with strain and strain rate derived from color tissue Doppler imaging. BNP was related to myocardial function and the presence or absence of global diastolic dysfunction. By conventional Doppler criteria, 34 patients had normal left ventricular diastolic function and 38 had isolated diastolic dysfunction. BNP values were higher in patients with diastolic dysfunction (46 +/- 48 vs 20 +/- 20 pg/ml, p=0.004) and were related independently to blood pressure, systolic strain rate, left atrial function (p<0.01 for all), and age (p=0.015). Patients with diastolic dysfunction and pseudonormal filling had higher BNP levels compared with impaired relaxation (89 +/- 47 vs 35 +/- 42 pg/ml, p=0.001). However, 79% of patients with diastolic dysfunction had BNP levels within the normal range. We conclude that in ambulatory hypertensive patients with symptoms suggestive of mild HF and normal ejection fraction, BNP is related to atrial and ventricular systolic parameters, blood pressure, and age. Although elevated in the presence of diastolic dysfunction, the BNP level mostly is in the normal range and, therefore, has limited diagnostic value in stable patients with suspected diastolic HF.

Topics: Biomarkers; Diastole; Dyspnea; Echocardiography, Doppler; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Exertion; Prospective Studies; ROC Curve; Systole; Ventricular Function, Left

Moxonidine, an imidazoline receptor agonist that acts centrally to inhibit sympathetic activity, has been shown to reduce effectively blood pressure, fasting insulin levels, and free fatty acids. In this study, we investigated the long-term effects of moxonidine treatment on cardiac natriuretic peptides (ANP and BNP) in Spontaneously Hypertensive Obese Rats (SHROBs), a rat model that resembles human Syndrome X. SHROBs expressing spontaneous hypertension, insulin resistance, and genetic obesity (weight 590 +/- 20 g, at 30 weeks) received moxonidine in chow at 4 mg/kg/day for 15 days. Moxonidine significantly reduced not only systolic blood pressure (187 +/- 6 versus 156 +/- 5 mm Hg, P < 0.05) but also plasma ANP (1595 +/- 371 versus 793 +/- 131 pg/mL, P < 0.05) and BNP (22 +/- 3 versus 14 +/- 1 pg/mL, P < 0.04), without influencing cardiac content of either peptide. Semi-quantitative PCR revealed that atrial ANPmRNA/GAPDHmRNA decreased to 39% 6 10% of pair-fed controls, P < 0.03. In left ventricles, moxonidine also decreased ANP mRNA to 69% +/- 7% and BNP mRNA to 74% +/- 6% of control, P < 0.02, but right ventricular ANP and BNP mRNA were not affected. These findings indicate that chronic inhibition of sympathetic activity with moxonidine in SHROB is associated with decreased ventricular natriuretic peptide transcription, consistent with the cardioprotective effects of moxonidine given the role of ANP and BNP as markers of cadiac disease. Moxonidine also improves the metabolic profile in these rats, thus it may be considered the drug of choice in treatment of metabolic syndrome X.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Ventricles; Humans; Hypertension; Imidazoles; Male; Natriuretic Peptide, Brain; Obesity; Rats; Rats, Inbred SHR

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones that regulate blood pressure and volume, and exert their biological actions via the natriuretic peptide receptor-A gene (Npr1). Mice lacking Npr1 (Npr(-/-)) have marked cardiac hypertrophy and fibrosis disproportionate to their increased blood pressure. This study examined the relationships between ANP and BNP gene expression, immunoreactivity and fibrosis in cardiac tissue, circulating ANP levels, and ANP and BNP mRNA during embryogenesis in Npr1(-/-) mice. Disruption of the Npr1 signaling pathway resulted in augmented ANP and BNP gene and ANP protein expression in the cardiac ventricles, most pronounced for ANP mRNA in females [414 +/- 57 in Npr1(-/-) ng/mg and 124 +/- 25 ng/mg in wild-type (WT) by Taqman assay, P < 0.001]. This increased expression was highly correlated to the degree of cardiac hypertrophy and was localized to the left ventricle (LV) inner free wall and to areas of ventricular fibrosis. In contrast, plasma ANP was significantly greater than WT in male but not female Npr1(-/-) mice. Increased ANP and BNP gene expression was observed in Npr1(-/-) embryos from 16 days of gestation. Our study suggests that cardiac ventricular expression of ANP and BNP is more closely associated with local hypertrophy and fibrosis than either systemic blood pressure or circulating ANP levels.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Cardiomyopathies; Embryo, Mammalian; Female; Fibrosis; Guanylate Cyclase; Heart Ventricles; Hypertension; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor; Reference Values; RNA, Messenger

The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We recently characterized the exon/intron organization of the human type A NP receptor (hNPRA) gene. The aim of this study was to isolate the genetic markers according to the organization of this gene, and to study the association between this gene and essential hypertension. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we identified a novel missense mutation, M3411, consisting of a methionine (ATG) to isoleucine (ATC) substitution at nucleotide 1023 in exon 3. Computer-aided three-dimensional structural analysis suggested that M341 exists in the loop between two alpha-helices, and that the mutation may influence receptor activities by altering the conformation of the alpha-helices. We performed an association study of the mutation in 210 essential hypertension (EH) patients and 210 normotensive controls. The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. The ratio of plasma brain natriuretic peptide (BNP)/mean blood pressure of the C/C genotype was significantly higher than that of the G/G genotype or the G/C genotype. We conclude that the significance of homozygous M3411 mutation in exon 3 is worth investigating for its possible association with EH.

Topics: Adult; Aged; Atrial Natriuretic Factor; Dimerization; Exons; Genotype; Guanylate Cyclase; Humans; Hypertension; Male; Middle Aged; Mutation, Missense; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Pressure; Calcium Channel Blockers; Cilazapril; Dihydropyridines; Drug Therapy, Combination; Heart Failure; Hypertension; Kidney; Natriuretic Peptide, Brain; Organ Size; Rats; Receptor, Angiotensin, Type 1; RNA, Messenger; Survival Rate; Systole; Transforming Growth Factor beta

Guanylyl cyclase (GC)-A, a natriuretic peptide receptor, lowers blood pressure and inhibits the growth of cardiac myocytes and fibroblasts. Angiotensin II (Ang II) type 1A (AT1A), an Ang II receptor, regulates cardiovascular homeostasis oppositely. Disruption of GC-A induces cardiac hypertrophy and fibrosis, suggesting that GC-A protects the heart from abnormal remodeling. We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice.. We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866. The cardiac hypertrophy and fibrosis of GC-A-KO mice were greatly improved by deletion or pharmacological blockade of AT1A. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, transforming growth factors beta1 and beta3, were also strongly inhibited. Furthermore, stimulation of AT1A by exogenous Ang II at a subpressor dose significantly exacerbated cardiac hypertrophy and dramatically augmented interstitial fibrosis in GC-A-KO mice but not in wild-type animals.. These results suggest that cardiac hypertrophy and fibrosis of GC-A-deficient mice are partially ascribed to an augmented cardiac AT1A signaling and that GC-A inhibits AT1A signaling-mediated excessive remodeling.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensinogen; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Cardiomegaly; Collagen; Fibrosis; Gene Targeting; Guanylate Cyclase; Heart Rate; Heart Ventricles; Hypertension; Imidazoles; Mice; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Organ Size; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Tetrazoles; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factor beta2; Ventricular Remodeling

Brain natriuretic peptide (BNP) is increased and it is also released during exercise in hypertension, but its biologic role is unclear. However, since BNP is released from the left ventricule and it is known to reduce left ventricular filling pressure, it is possible that it exerts a favorable effect on exercise performance. We studied the relationship between endogenous BNP release and exercise capacity in hypertension with reference to left ventricular hypertrophy (LVH). Cardiopulmonary exercise study was carried out in 2 groups of hypertensives, 24 [16 men, aged 50 (SD 11) years] of whom had echocardiographic LVH and 25 [16 men, aged 41 ( 12)] who did not have LVH. In multiple regression analyses, the major determinants of peak oxygen uptake (VO max) were age (-), sex (male), peak exercise systolic BP (+) and post-exercise BNP (-). For the predicted adjusted %VO max as a measure of individualised exercise capacity, the significant predictors were the exercise-induced BNP rise (-) (p = 0.0003) and peak exercise systolic BP (+) (p = 0.001). In other words, subjects with greater myocardial dysfunction had a greater rise in BNP during exercise. LVH did not however relate to exercise capacity. The baseline, post-exercise and the % rise in BNP (pmol/L) with exercise were not statistically different in those with LVH compared with those without (median values of 11.2, 14.6 and 133% versus 10.6, 11.5 and 120% respectively). Similarly, there were no significant differences in exercise capacity between the groups: exercise time, oxygen uptakes at ventilatory threshold and at peak exercise (VO max) were 10.8 (2.5) min, 15.8 (4.6) and 33.6 (7.6) ml/min/kg in the LVH group against 11.4 (2.9) min, 18.6 (5.2) and 36 (11.1) ml/min/kg in the non-LVH group respectively. The estimated VO max was not different from that predicted from age, sex, weight and height in either group suggesting preserved exercise capacity in these subjects as a whole. In Conclusion, BNP may potentially act as a homeostatic mechanism that helps to limit exercise incapacity in hypertension irrespective of LVH.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Exercise Test; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Ventilation; Regression Analysis; Sex Factors

Topics: Antihypertensive Agents; Aorta; Blood Pressure; Blood Pressure Determination; Female; Humans; Hypertension; Male; Natriuretic Peptide, Brain

A positive correlation has been previously documented between B-type natriuretic peptide (BNP) levels and left ventricular mass index (LVMI) in hypertensive patients. We evaluated 8 cycling athletes, 8 healthy age-matched controls; 17 hypertensive patients and 7 age-matched controls. LVMI was significantly higher in athletes and hypertensive patients than in their controls. Plasma levels of BNP in hypertensive patients were significantly higher than in athletes and their age-matched controls. No significant difference was found between athletes and their controls. Cycling athletes had significantly larger LVMI than hypertensive patients and controls, without elevated BNP levels. These results suggest that BNP levels are elevated in patients with increased LVM due to hypertension but not in physiologically increased LVM. Whether elevated BNP levels in athletes is a sign of structural heart disease merits further investigation.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Sports; Statistics as Topic

We examined the effects of aging and hypertensive left ventricular hypertrophy on the plasma level of brain natriuretic peptide (BNP), and assessed BNP as a risk marker for incident hypertensive cardiovascular events. One hundred and eighty-five hypertensive patients were echocardiographically divided into a hypertensive group with normal left ventricular mass (n=96; age range, 37-86 years; left ventricular mass, 97+/-14 g/m2) and a hypertensive group with left ventricular hypertrophy (n=89; 37-90 years; 140+/-20 g/m2). Forty-four normotensive subjects served as the normotensive group (32-84 years; 91+/-15 g/m2). We examined the association of age with BNP in the three groups and also evaluated BNP as a risk marker for incident cardiovascular events by following up all patients for 40 months. All three groups demonstrated a significant positive relationship between age and BNP. The slope of the relation between age and BNP was steepest in the hypertensive group with left ventricular hypertrophy (p<0.0001 vs. the other two groups). Multiple regression analysis revealed that age, pulse pressure and left ventricular mass index were significantly associated with the increase in BNP. Multivariate Cox proportional hazards regression analysis, which was used to assess the potential association of age, pulse pressure, left ventricular mass index and BNP with the cardiovascular events during follow-up, revealed the highest correlation between BNP and incident cardiovascular events (risk ratio=1.011; p=0.0011). BNP, which is synergistically increased with aging and left ventricular hypertrophy, may be an important risk marker for hypertensive cardiovascular events.

Topics: Aged; Aging; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Catecholamines; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Incidence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Renin; Risk Factors

Messenger RNA of brain natriuretic polypeptide (BNP) is detected in both the atrium and the ventricle in vitro. Clinical usefulness has been shown in assessment of BNP level in patients with left ventricular hypertrophy; however, few studies have reported the role of the atrium and ventricle separately in the secretion of BNP from the hypertrophied heart.. To investigate how the atrium and ventricle secrete natriuretic peptides by comparing the regional concentration of atrial natriuretic polypeptide (ANP) or BNP in the hypertrophied heart with clinical parameters.. ANP and BNP were measured in blood samples from the aortic root, the anterior interventricular vein (AIV) and the coronary sinus in 12 control subjects, 10 subjects with hypertensive hypertrophy and eight with non-obstructive hypertrophic cardiomyopathy. The difference in concentration between the aortic root and the AIV and that between the AIV and the coronary sinus was calculated to estimate ventricular and atrial secretion, respectively.. Plasma BNP levels correlated significantly with left ventricular mass index, pulmonary artery wedge pressure, stroke volume and left atrial dimension. Stepwise multiple regression analysis identified BNP from the atrium, not the ventricle, as an independent predictor of left ventricular mass.. These data suggest that atrium-derived BNP is a significant predictor of left ventricular mass index in patients with left ventricular hypertrophy. The atrium-derived component contributes significantly to the elevation of plasma BNP level, reflecting atrial pressure and volume loading in left ventricular hypertrophy without systolic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Heart Atria; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis

We investigated the effect of long-term in vivo blockade of the ET-1 receptor subtype B (ET(B)) with A-192621, a selective ET(B) antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the renin-angiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET(B) blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET(B) blockade/DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. Collagen III and beta-myosin heavy chain gene expression were enhanced in both the right and the left ventricle of DOCA-salt hypertensive rats. The results of this study suggest that the ET(B) receptor does not participate directly in the modulation of atrial or ventricular NP gene expression and that this receptor mediates a protective cardiovascular function. ET(B) blockade can induce significant ventricular hypertrophy without an increase in ANF or brain NP gene expression.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Desoxycorticosterone; Endothelin Receptor Antagonists; Gene Expression Regulation; Heart Ventricles; Hypertension; Natriuretic Peptide, Brain; Organ Size; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B; Sodium, Dietary; Transcription, Genetic

B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and plasma BNP peptide levels are normal, despite the persistent increase in blood pressure and ventricular hypertrophy. In this study, the role of transcriptional mechanisms in the regulation of BNP gene expression were studied in angiotensin (Ang) II-induced hypertension by injecting DNA constructs containing the BNP promoter (-2200 to 75 bp of the transcriptional start site) linked to luciferase reporter into rat myocardium. Ang II was administered to conscious rats via intravenous infusion for 2 hours or by subcutaneous minipumps for 6 hours, 12 hours, 3 days, 1 week, and 2 weeks. Ang II increased blood pressure and cardiac mass and induced changes in diastolic function. The left ventricular BNP mRNA levels increased 2.2-fold (P<0.001) at 2 hours and peaked at 12 hours (5.2-fold, P<0.001). Thereafter, BNP mRNA levels decreased (1.8-fold induction at 3 days, P<0.05) and returned to control levels at 1 week, despite persistent hypertension and myocardial hypertrophy. Left ventricular BNP peptide concentrations followed the changes in BNP mRNA levels. The BNP promoter was activated 2.7-fold (P<0.05) at 2 hours and remained upregulated up to 2 weeks (2.8-fold, P<0.05) during Ang II infusion, except at 12 hours. These results indicate that posttranscriptional control plays a major role in the regulation of ventricular BNP gene expression in Ang II-induced hypertension.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Echocardiography; Gene Expression Regulation; Heart Rate; Heart Ventricles; Hypertension; Male; Natriuretic Peptide, Brain; Organ Size; Promoter Regions, Genetic; Protein Binding; Rats; Rats, Sprague-Dawley; RNA Processing, Post-Transcriptional; RNA, Messenger; Transcription Factor AP-1

Midwall fractional shortening (MFS) is a useful index to evaluate left ventricular myocardial function in patients with essential hypertension. The study investigated the prevalence and characterization of low MFS in hemodialysis patients.. MFS was calculated from M-mode echocardiograms in 67 patients (34 males, 33 females) receiving maintenance hemodialysis in whom fractional shortening was normal. Plasma levels of atrial and brain natriuretic peptides were also measured in these patients before and after hemodialysis. MFS was evaluated by stress-corrected MFS (ratio of observed to predicted MFS). The relationship of MFS to circumferential end-systolic stress in 122 healthy subjects was used to calculate the predicted MFS.. Stress-corrected MFS was depressed in 18 of the 67 patients (26.9%). In the low MFS group, duration of hypertension was significantly longer (p < 0.05), wall thickness was significantly greater (p < 0.001), left ventricular dimension was significantly smaller (p < 0.0001), and relative wall thickness was significantly greater (p < 0.0001) than in the normal MFS group. Reduction of brain natriuretic peptide level by hemodialysis in the low MFS group was significantly higher (p < 0.05) than in the normal MFS group.. Depression of stress-corrected MFS may be common in hemodialysis patients. Long duration of hypertension and concentric geometry of the left ventricle occur in patients with low MFS.

Topics: Aged; Atrial Natriuretic Factor; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Renal Dialysis; Renal Insufficiency; Ventricular Function, Left

We examined whether Ca2+ channel blockers inhibit the activation of the Ca2+-dependent phosphatase calcineurin and the development of cardiac hypertrophy in spontaneously hypertensive rats (SHR). We randomly divided 12-week-old SHR into three groups, one each receiving vehicle, bolus injection or continuous infusion of nifedipine (10 mg/kg/day) from 12 to 24 weeks of age. Systolic blood pressure (BP) and heart rate were measured every week after the treatment using the tail-cuff plethysmography method. After 4, 8 and 12 weeks of treatment, 6 rats of each group were subjected to examinations that included an assay for calcineurin activity in the heart, magnetic resonance imaging (MRI), histology and Northern blot analysis. Continuous infusion of nifedipine consistently reduced BP, whereas bolus injection resulted in a fluctuation of BP. Continuous infusion of nifedipine not only reduced left ventricular mass but also decreased the transverse diameter of cardiomyocytes, interstitial fibrosis and the expression of the atrial natriuretic peptide and brain natriuretic peptide genes in the heart, while bolus injection of nifedipine did not significantly attenuate any of these hypertrophic responses in SHR. The activity of calcineurin in the heart was strongly suppressed by continuous but not bolus infusion of nifedipine in SHR. The results indicate that continuous blockade of Ca2+ channels with nifedipine effectively suppresses the development of cardiac hypertrophy in SHR, possibly through inhibition of the calcineurin activity.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Calcineurin Inhibitors; Calcium Channel Blockers; Calcium Channels, L-Type; Cardiomegaly; Fibrosis; Gene Expression; Heart Rate; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Nifedipine; Rats; Rats, Inbred SHR

This study was designed to examine whether aldosterone is produced from the hearts of patients with essential hypertension without left ventricular systolic dysfunction (LVSD). The study population consisted of 20 patients with essential hypertension without LVSD and 22 control subjects. Plasma levels of aldosterone, serum ACE activity, and B-type natriuretic peptide levels were measured in the anterior interventricular vein (AIV), coronary sinus, and aortic root during cardiac catheterization. The plasma aldosterone levels were significantly higher in AIV and coronary sinus than in aortic root (99+/-11 versus 88+/-10 pg/mL, P<0.01, and 100+/-12 versus 88+/-10 pg/mL, P<0.01, respectively) in the hypertension group. On the other hand, there were no significant differences in aldosterone levels for these sites in the control group. There were no significant differences in ACE activity levels between aortic root, AIV, and coronary sinus in either the hypertension or control group. The levels of B-type natriuretic peptide were significantly higher in AIV than in aortic root in both groups. The difference in aldosterone levels between AIV and aortic root (Delta Aldo[AIV-Ao]) had a significant positive correlation with the difference in ACE activity between AIV and aortic root (DeltaACE[AIV-Ao]) (r=0.501, P<0.05) in the hypertension group. Both Delta Aldo[AIV-Ao] and DeltaACE[AIV-Ao] had a significant positive correlation with diastolic blood pressure (r=0.498, P<0.05; r=0.577, P<0.01, respectively) in the hypertension group. We conclude that production of aldosterone is activated in the left ventricles in patients with essential hypertension without LVSD in proportion to the severity of hypertension.

Topics: Aldosterone; Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A

This study investigated the comparative effects of losartan and amlodipine on the activation of the sympathetic nervous system, renin-angiotensin-aldosterone system (R-A-A system) and brain natriuretic peptide (BNP) in patients with essential hypertension. Twenty-four elderly patients who had received more than 12 months of antihypertensive treatment with amlodipine participated in this study. The treatment regimen of 5 mg/day amlodipine was changed to 50 mg/day losartan. Plasma catecholamines (norepinephrine, epinephrine and dopamine), active renin, aldosterone and BNP concentration were measured before and after an average of 5 months of losartan treatment. After losartan treatment, blood pressures were not changed, suggesting the comparable effect of 50 mg losartan and 5 mg amlodipine on elevated blood pressure. Losartan significantly reduced norepinephrine (799 +/- 277 pg/mL vs. 692 +/- 268 pg/mL, p < 0.05) and aldosterone concentration (81.2 +/- 35.3 pg/mL vs. 55.2 +/- 17.7 pg/mL, p < 0.01), whereas there were not any changes in BNP concentrations. These findings suggested that losartan might be superior to amlodipine in prevention of chronic or intermittent sympathetic hyperactivity and enhanced R-A-A system.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Heart Rate; Humans; Hypertension; Losartan; Natriuretic Peptide, Brain; Renin-Angiotensin System; Sympathetic Nervous System

Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks but showed aldosterone breakthrough after 8 weeks of AT1A administration. Plasma angiotensin II concentration was significantly elevated, whereas no change was seen in plasma ACTH or serum potassium. The mechanism(s) of aldosterone breakthrough were investigated by giving high doses of candesartan (3 mg/kg per day PO), dexamethasone (200 microg/kg per day IP), or the AT2 antagonist (PD123319, 10 mg/kg per day SC) during the last week of the 24-week AT1A treatment period. Dexamethasone and AT2 antagonist but not high-dose AT1A produced a significant decrease in PAC, with a larger decrease produced by the AT2 antagonist. To clarify the effects of the residual aldosterone, effects of coadministration of low-dose spironolactone (10 mg/kg per day SC), an aldosterone antagonist, on left ventricular hypertrophy and expression of brain natriuretic peptide mRNA were determined. Low-dose spironolactone further improved left ventricular hypertrophy and brain natriuretic peptide mRNA expression despite no additional depressor effect. These results suggest that aldosterone breakthrough occurs during long-term AT1A therapy, mainly by an AT2-dependent mechanism. Residual aldosterone may attenuate the cardioprotective effects of AT1A.

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Body Weight; Corticosterone; Dexamethasone; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypertension; Imidazoles; Male; Natriuretic Peptide, Brain; Prodrugs; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Spironolactone; Stroke; Tetrazoles; Time Factors

To verify in a unitary view whether autonomic control of heart rate and cardiac structure and function are modified early in offspring of hypertensive families.. We selected 87 age- and sex-matched young normotensive subjects with (n = 45) and without (n = 42) a family history of hypertension who underwent evaluations of arterial pressure, time-domain parameters of autonomic heart rate control (24-h ECG monitoring), spectral baroreflex sensitivity, left ventricular geometry and function (echo-Doppler) and plasma brain natriuretic peptide levels (BNP). The group with a family history of hypertension significantly differed from their counterparts for systolic pressure (119 +/- 11 versus 114 +/- 9 mmHg, P< 0.05), heart rate (RR interval, 766 +/- 64 versus 810 +/- 93 ms, P< 0.05), heart rate variability [the standard deviation of normal RR intervals (SDNN), 147 +/- 29 versus 171 +/- 33 ms, P < 0.051, diastolic function (isovolumetric relaxation time, 65 +/- 9 versus 60 +/- 8 ms, P< 0.05) and BNP (23 +/- 13 versus 37 +/- 10 pg/ml, P< 0.05). Baroreflex sensitivity values did not differ between the two groups. When gender was considered, all the above-mentioned measures, as well as baroreflex sensitivity, were significantly different between males with and without a family history of hypertension but not between females, except for BNP, which was lower in males and females with a history of hypertension (males, 24 +/- 11 versus 38 +/- 8 pg/ml, P< 0.01; females 21 +/- 14 versus 36 +/- 13 pg/ml, P < 0.05).. Male, but not female, hypertensive offspring have modified diastolic function and autonomic control of heart rate; BNP is the only parameter able to characterize hypertensive offspring independently from the influence of gender. This provides the hypothesis that the impaired production of this hormone could play a primary role in the pre-hypertensive state.

Topics: Adolescent; Adult; Age Factors; Autonomic Nervous System; Baroreflex; Diastole; Echocardiography, Doppler; Electrocardiography; Female; Genetic Predisposition to Disease; Heart Rate; Heart Ventricles; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; ROC Curve; Sex Factors; Ventricular Function, Left

The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood). In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber-specific factors.

Topics: Age Factors; Aging; Animals; Atrial Natriuretic Factor; Heart Atria; Heart Ventricles; Hypertension; In Situ Hybridization; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results-- Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II, ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and diastolic (tau) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (*P<0.05 versus controls: 139+/-4* versus 123+/-4 mm Hg), week 5 (174+/-7* versus 124+/-4 mm Hg), and week 12 (181+/-12* versus 124+/-4 mm Hg). LV mass index was increased in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees was preserved in HTN-5wk and HTN-12wk. tau was increased in HTN-5wk (50+/-3* ms) and HTN-12wk (62+/-10* ms) dogs compared with sham (41+/-2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different from controls.. Systemic HTN induces LV hypertrophy, myocardial fibrosis, and isolated diastolic dysfunction in the absence of local or systemic activation of Ang II or ET. These findings suggest that load is the prevailing stimulus for the structural and functional changes associated with early hypertensive heart disease.

Topics: Angiotensin II; Animals; Catecholamines; Diastole; Disease Models, Animal; Dogs; Endothelin-1; Heart Ventricles; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Kidney; Natriuretic Peptide, Brain; Propranolol; Renin; Systole; Ventricular Dysfunction, Left

We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice.. The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases.. Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Heart Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure.. Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5).. The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased.. BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Echocardiography; Fibrosis; Heart Ventricles; Hemodynamics; Hypertension; Male; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Rats; Rats, Inbred Dahl; RNA, Messenger; Ventricular Remodeling

To identify the mechanisms that couple hemodynamic stress to alterations in cardiac gene expression, DNA constructs containing the rat B-type natriuretic peptide (BNP) promoter were injected into the myocardium of rats, which underwent bilateral nephrectomy or were sham-operated. Ventricular BNP mRNA levels were induced about 4-fold; and the BNP reporter construct containing the proximal 2200 bp, 5-fold, in response to 1-d nephrectomy. Deletion of sequences between bp -2200 and -114 did not affect basal or inducible activity of the BNP promoter. An activator protein-1-like site and two tandem GATA elements are located within this 114-bp sequence. Both deletion and mutation of the AP-1-like motif decreased basal activity but did not abolish the response to nephrectomy. In contrast, mutation or deletion of -90 bp GATA-sites abrogated the response to hemodynamic stress. The importance of these GATA elements to BNP promoter activation was further confirmed by the corresponding 38-bp oligonucleotide conferring hemodynamic stress responsiveness to a minimal BNP promoter. In gel mobility shift assays, nephrectomy increased left ventricular BNP GATA4 binding activity significantly. In conclusion, GATA elements are necessary and sufficient to confer transcriptional activation of BNP gene in response to hemodynamic stress.

Topics: Amino Acid Motifs; Animals; Atrial Natriuretic Factor; DNA-Binding Proteins; GATA4 Transcription Factor; GATA6 Transcription Factor; Gene Expression Regulation; Heart; Heart Ventricles; Hemodynamics; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stress, Physiological; Transcription Factors; Transcriptional Activation; Up-Regulation

Topics: Amlodipine; Antihypertensive Agents; Atenolol; Atrial Natriuretic Factor; Bendroflumethiazide; Cardiomegaly; Endothelin-1; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Perindopril; Procollagen; Randomized Controlled Trials as Topic

To investigate serum levels of amino-terminal pro-brain natriuretic peptide (Nt pro-BNP) as an index of left-ventricular function in normal pregnancy and pregnancies complicated by hypertension and also to investigate levels in both primigravid and multigravid women.. Women with hypertension in pregnancy (at least two readings of systolic blood pressure > 140 mm Hg and diastolic blood pressure > 90 mm Hg) (n = 24) and normotensive women (n = 42) were included in the study. Serum Nt pro-BNP was measured using an enzyme-linked immunosorbent assay technique.. The median serum Nt pro-BNP level in pregnancies complicated by hypertension was 420 fmol/L, which was significantly greater than that measured in samples obtained from normotensive women in pregnancy (340 fmol/L) (p = 0.03). There was a nonsignificant trend toward increased levels in proteinuric as compared to nonproteinuric hypertension in pregnancy. Multigravida had higher Nt pro-BNP levels (n = 26; median Nt pro-BNP = 358 fmol/L) than primigravida (n = 16; median Nt pro-BNP = 278 fmol/L) (p = 0.01) in association with normal pregnancy. Multigravida also demonstrated a dramatic rise in serum Nt pro-BNP levels in association with hypertension in pregnancy (n = 13; median Nt pro-BNP = 572 fmol/L) as compared to normal pregnancy (n = 26; median Nt pro-BNP = 358 fmol/L) (p = 0.009).. Serum Nt pro-BNP is elevated in women with hypertensive disorders of pregnancy, indicating elevated left-ventricular filling pressures. Measured serum levels in both normal and hypertensive pregnancy are higher in multigravida than in primigravida.

Topics: Adult; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular

To examine the relation between plasma concentration of the N terminal of the precursor of brain natriuretic peptide (NT proBNP), left ventricular hypertrophy (LVH), and left ventricular systolic dysfunction (LVSD) in patients with a history of hypertension.. Prospective study.. Teaching hospital based study.. NT proBNP concentrations were determined in five groups of individuals. Group 1: 15 echocardiographic normal controls; group 2: 22 patients with hypertension, normal left ventricular systolic function, and no LVH; group 3: 24 patients with hypertension, normal left ventricular systolic function, and LVH; group 4: 13 patients with history of hypertension, no history of ischaemic heart disease, and left ventricular wall motion index (WMI) between 1.9-1.3; and group 5:17 patients with a history of hypertension, no history of ischaemic heart disease, and WMI < 1.2.. Median (range) NT proBNP concentrations (in fmol/ml) for groups 1-5, respectively, were: 129.4 (53.6-159.7), 147.4 (54.3-730. 5), 137.1 (35.8-403.9), 356.7 (124.4-934.4), and 493.5 (248.9-909). Mean log NT proBNP differed among all five groups (p < 0.0001), and between groups 4 and 5 versus groups 1-3 (p < 0.0001), and group 4 versus group 5 (p = 0.02) only.. The results suggest that the presence of hypertension with or without LVH (and normal left ventricular systolic function) does not affect NT proBNP concentrations. Moreover, there is a significant rise in NT proBNP only when LVSD develops in hypertension. Thus, NT proBNP remains a useful diagnostic aid for LVSD, even in hypertensive patients.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prospective Studies; Regression Analysis; Ventricular Dysfunction, Left

Topics: Exercise Test; Humans; Hypertension; Hypertrophy, Left Ventricular; Jogging; Natriuretic Peptide, Brain; Risk Factors; Running; Sports

To examine whether plasma levels of brain natriuretic peptide identify hypertensive patients at risk for progressive cardiac hypertrophy.. We examined the association between plasma brain natriuretic peptide levels and left ventricular structural changes in 54 hypertensive patients and 28 normotensive control subjects. Patients were divided into those with elevated (n = 14) or normal (n = 40) levels of brain natriuretic peptide, based on a cutoff level of 41 pg/mL (2 SD above the mean in the control subjects). Left ventricular function and geometry were assessed echocardiographically at baseline and follow-up.. At baseline, initial left ventricular chamber size, wall thickness, and systolic function did not differ between the hypertensive patients and normotensive subjects. After a mean (+/- SD) follow-up of 9 +/- 3 months, blood pressure was relatively unchanged in the hypertensive patients with normal brain natriuretic peptide levels, whereas there were significant increases in systolic blood pressure and pulse pressure (both P <0.05 versus baseline) in patients with elevated brain natriuretic peptide levels. Moreover, left ventricular midwall systolic function had decreased significantly at follow-up in those with elevated levels (P <0.05 versus baseline). At follow-up, the hypertensive patients with elevated brain natriuretic peptide levels had a significantly greater left ventricular mass index and relative wall thickness than those with normal levels. Multiple regression analyses determined that only initial plasma brain natriuretic peptide was significantly (P <0.01) associated with subsequent left ventricular hypertrophy.. Plasma brain natriuretic peptide levels may identify hypertensive patients who are likely to have progressive cardiac hypertrophy.

Topics: Aged; Case-Control Studies; Disease Progression; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk

To determine the role of endothelin-1 (ET-1) in the upregulation of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) observed in deoxycorticosterone acetate (DOCA)-salt hypertension, the selective ET-1 type-A receptor (ET(A)) antagonist ABT-627 was chronically administered to normal controls and hypertensive rats. Chronic ET(A) blockade in DOCA-salt-treated rats prevented the increase in blood pressure and circulating natriuretic protein (NP) levels and partially prevented left ventricular hypertrophy. The changes observed in NP gene expression in the atria were not affected by ABT-627. In the ventricles, ABT-627 reduced NP gene expression. Rats receiving the ET(A) antagonist alone showed reduced left ventricular NP gene expression. ABT-627 did not affect ventricular collagen III gene expression but enhanced left ventricular alpha-myosin heavy chain expression. These findings suggest that in vivo, ventricular but not atrial NP production is regulated by ET-1. This difference in response between atrial and ventricular NP gene expression to ET(A) receptor blockade is similar to that observed by us after applying angiotensin-converting enzyme inhibitors in other hypertensive models. In general therefore, atrial NP gene expression may not be as sensitive to the endocrine environment as is ventricular NP gene expression.

Topics: Animals; Atrasentan; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Desoxycorticosterone; Endothelin Receptor Antagonists; Gene Expression Regulation; Heart; Heart Ventricles; Hypertension; Male; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Organ Size; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Sodium, Dietary; Transcription, Genetic

In the elderly, left ventricular hypertrophy (LVH) is a powerful risk factor for cardiovascular events and cardiovascular death. The purpose of the present study is to investigate the effect of long-term effective blood pressure control with the angiotensin-converting enzyme (ACE) inhibitor temocapril on left ventricular (LV) mass and function indices and the circulating concentration of the cardiac hormone brain natriuretic peptide (BNP) in elderly hypertensives with LVH. Temocapril treatment was administered for 1 year to 11 elderly hypertensives (mean age, 72 years) with LVH. Cardiac dimensions and circulating concentrations of BNP were monitored before initiation of treatment and after 1 year of treatment. At entry, BNP levels were positively correlated with the LV mass index, but were not correlated with the mean blood pressure, LV ejection fraction, or E/A ratio (the ratio of peak transmitral flow velocity in early diastole, peak E, to that in late diastole, peak A). After 1 year, temocapril treatment resulted in effective control of blood pressure. The treatment did not affect the LV ejection fraction, but modestly increased the E/A ratio. Temocapril significantly reduced septal and posterior wall thickness and the LV mass index. BNP significantly declined after 1 year. Changes in BNP were significantly related to changes in the LV mass index, but were not related to changes in the mean blood pressure, LV ejection fraction, or E/A ratio. The results suggest that long-term ACE inhibitor treatment with temocapril can induce the regression of LV mass and reduce elevated plasma BNP in elderly hypertensive patients with LVH. In this study, changes in BNP reflected the magnitude of regression of LVH.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Ventricular Function, Left

We examined the effect of a hypocaloric diet on adrenomedullin (AM), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in 12 obese patients with essential hypertension (age, 48-81 years; body mass index, 26-34 kg/m2). For the initial week, a standard diet of 2000 kcal/day was given, followed by 3 weeks of a hypocaloric diet of 850 kcal/day, with a constant intake of sodium. The patients lost 3.7 +/- 0.2 kg body weight during the hypocaloric diet period (p < 0.0001). The decrease in blood pressure during the study period was 10.3 +/- 3.6 mmHg systole (p = 0.017) and 4.2 +/- 3.2 mmHg diastole (NS). Plasma AM concentration was decreased significantly from 4.88 +/- 0.46 to 3.97 +/- 0.38 pmol/l by the hypocaloric diet (p = 0.004). Plasma ANP and BNP concentrations were also decreased significantly by the hypocaloric diet (p = 0.042 for each). These results demonstrate, for the first time, that plasma AM concentration as well as plasma ANP and BNP concentrations are decreased by a hypocaloric diet in obese patients with essential hypertension. These vasodilator peptides may act against further elevation in blood pressure in obese patients with essential hypertension.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Energy Intake; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptides

-Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium-dependent relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8; pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.

Topics: Amino Acid Substitution; Animals; Atrial Natriuretic Factor; Base Sequence; Brain; Brain Ischemia; Cells, Cultured; Cerebrovascular Disorders; Chromosome Mapping; DNA Primers; Exons; Genetic Markers; Genetic Predisposition to Disease; Hypertension; Introns; Male; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Point Mutation; Polymerase Chain Reaction; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley

Adrenomedullin (AM), a potent vasodilator and natriuretic peptide, is found in human blood. To investigate the pathophysiological role of AM in essential and malignant hypertension (EHT and MHT), we measured the plasma concentrations of AM in patients with EHT of WHO stage I or II (n = 42) and in those with MHT (n = 9) by a specific radioimmunoassay, and compared these concentrations with those in normotensive controls (n = 46). The plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) in these subjects were also measured by immunoradiometric assays, and their relations to plasma AM were examined. The plasma AM level in the EHT patients (7.15+/-0.21 pmol/l, mean+/-SEM) was significantly (p < 0.01) higher than that in the normotensive controls (6.14+/-0.25 pmol/l), and a further elevation was observed in the MHT patients (14.1+/-3.8 pmol/l). Similar elevations of plasma ANP and BNP were seen in the two patient groups. The plasma AM level significantly (p < 0.01) correlated with not only the systolic (r = 0.44) and diastolic (r = 0.46) blood pressures, but also with the plasma levels of ANP (r = 0.43) and BNP (r = 0.43). The elevated plasma concentration of AM in the MHT patients decreased significantly (p < 0.05) after antihypertensive treatment, and the plasma ANP and BNP levels similarly declined. These results suggest that AM may participate, along with ANP and BNP, in mechanisms counteracting a further elevation of blood pressure in patients with EHT and MHT.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Calcitonin Gene-Related Peptide; Creatinine; Female; Humans; Hypertension; Hypertension, Malignant; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Radioimmunoassay; Renin

An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor.. ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored.. Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean +/- SD) serum ACE activity was significantly greater (P <0.05) in the DD (18 +/- 7 IU/L) group than in the II (7 +/- 4 IU/L) or ID (12 +/- 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (+/- SD) regression in posterior wall thickness was significantly less (P <0.05) in the DD group (-9% +/- 5%) than in the ID (-21% +/- 7%) and II (-21% +/- 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group (P <0.05).. Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Female; Genotype; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Polymorphism, Genetic

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Topics: Atrial Natriuretic Factor; Calcium Channel Blockers; Coronary Circulation; Diastole; Diuretics; Echocardiography; Echocardiography, Doppler, Pulsed; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Ventricular Dysfunction, Left

Although heme oxygenase (HO) has been suggested to be involved in the regulation of cardiovascular function through production of carbon monoxide (CO), the pathophysiological significance of HO in hypertensive organ damage remains unknown. We examined the effects of inducing HO-1 mRNA by stannous chloride (SnCl2) on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Chronic administration of SnCl2 resulted in a significant decrease in left ventricular (LV) weight/body weight ratio and LV brain natriuretic peptide (BNP) mRNA levels as a marker of cardiac hypertrophy and a significant increase in LV HO-1 mRNA levels and LV cGMP contents in SHR-SP/Izm, while there was no significant change in systemic blood pressure. These results provide the first evidence that induction of HO in the heart attenuates cardiac hypertrophy in load-independent mechanism in genetically hypertensive rats.

Topics: Animals; Blood Pressure; Body Weight; Cyclic GMP; Enzyme Induction; Heart Rate; Heart Ventricles; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hypertension; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Tin Compounds

We investigated whether plasma brain and atrial natriuretic peptide (BNP and ANP, respectively) levels could reflect left ventricular (LV) geometry and function in patients with mild to moderate essential hypertension. A positive correlation was found between LV mass index (LVMI) and plasma ANP levels in 84 untreated, hypertensive patients, but not between LVMI and plasma BNP levels. As compared with other geometric patterns, plasma BNP levels were increased in concentric hypertrophy, in which LVMI was increased and LV diastolic function was decreased. These data suggest that production of BNP was increased in hypertensive patients with concentric hypertrophy via LV overload or depression of diastolic function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Epinephrine; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Radioimmunoassay; Renin; Ventricular Remodeling

Hypertensive patients with heart abnormalities have increased risk of cardiovascular events. Brain natriuretic peptide is a natriuretic peptide mainly of ventricular origin produced in response to pressure and stretch. We hypothesise that brain natriuretic peptide could be a useful marker of cardiac remodelling in hypertensive patients. We studied 36 consecutive community mild-to-moderate hypertensive patients and 11 well-matched normotensive controls with respect to clinical characteristics, brain natriuretic peptide, creatinine and echocardiography parameters (M-mode, 2-D arid transmitral pulsed Doppler). Brain natriuretic peptide levels were significantly higher in hypertensive patients than in controls [36.54 (IQR: 38.61) vs. 10.30 (IQR: 13.20) pg ml(-1), p<0.0001] and it was correlated with left ventricular mass index. Hypertensive patients with impairment of diastolic filling had significantly higher brain natriuretic peptide concentrations than patients with no abnormalities on echocardiography [61.16 (45.38) vs. 31.27 (18.10) pg ml(-1), p=0.001]. Multivariate analysis showed that only diastolic dysfunction and left ventricular mass index were significantly and independently related with brain natriuretic peptide concentrations in this population. In conclusion, impairment of diastolic function and left ventricular mass index are related to brain natriuretic peptide levels, thus giving the insight that this peptide can be a marker of ventricular remodelling in hypertensive patients.

Topics: Aged; Biomarkers; Case-Control Studies; Creatinine; Echocardiography, Doppler, Pulsed; Female; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; ROC Curve; Ventricular Dysfunction, Left; Ventricular Remodeling

To study the effects of long-term treatment with the type 1 angiotensin (AT1) receptor antagonist losartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril, on cardiac adrenomedullin (ADM), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression.. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were given losartan (15 mg/kg per day) or enalapril (4 mg/kg per day) orally for 10 weeks. The effects of drugs on systolic blood pressure, cardiac hypertrophy, ANP, BNP and ADM mRNA and immunoreactive-ANP (IR)-ANP, IR-BNP and IR-ADM levels in the left ventricle and atria were compared.. Losartan and enalapril treatments completely inhibited the increase of systolic blood pressure occurring with ageing in SHR. The ratio of heart to body weight was reduced in both losartan- and enalapril-treated SHR and WKY rats. Treatment with losartan or enalapril reduced left ventricular ANP mRNA and IR-ANP in both strains, and ventricular BNP mRNA levels in SHR rats. Inhibition of ACE, AT1 receptor antagonism, changes in blood pressure or cardiac mass had no effect on left ventricular ADM gene expression in SHR and WKY rats. In addition, atrial IR-ANP and IR-ADM levels increased in SHR whereas IR-BNP levels decreased in WKY and SHR rats in response to drug treatments.. Our results show that ventricular ADM synthesis is an insensitive marker of changes in haemodynamic load or cardiac hypertrophy. Furthermore, the expression of ADM, ANP and BNP genes is differently regulated both in the left ventricle and atria in response to AT1 receptor antagonism and ACE inhibition.

Topics: Adrenomedullin; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Enalapril; Gene Expression; Heart; Hypertension; Losartan; Male; Natriuretic Peptide, Brain; Peptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Reference Values

We studied the role of angiotensin II in pressure overload-induced B-type natriuretic peptide (BNP) gene expression by using a double transgenic rat (dTGR) model, in which transgenic rats for the human angiotensinogen and renin genes are crossed. Pressure overload produced by [Arg8]-vasopressin (AVP) infusion (i.v., 0.05 microg/kg/min for 2 h) in conscious, chronically instrumented rats, resulted in a significantly greater increase in BNP mRNA levels in the left atrium of the dTGR rats than in Sprague-Dawley (SD) control rats (3.6- vs 1.6-fold, p < 0.05), while in the left ventricle there was no significant difference between the strains. In dTGR rats, the early activation of the BNP gene expression was associated with a decrease in immunoreactive BNP levels in the atrium (27.5%, p < 0.05), but not in the ventricle. In SD rats, ir-BNP levels did not change significantly in either atria or ventricles in response to AVP infusion. These results show that the pressure overload-induced activation of BNP gene expression differs between atrial and ventricular myocytes in the dTGR model of experimental hypertension.

Topics: Angiotensinogen; Animals; Animals, Genetically Modified; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Gene Expression; Heart Atria; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger

The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid.. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides.. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery.. The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074).. BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Topics: Aged; Atrial Natriuretic Factor; Autocrine Communication; Biomarkers; Cardiac Output, Low; Cardiac Volume; Coronary Artery Bypass; Coronary Disease; Diastole; Female; Hemodynamics; Humans; Hypertension; Male; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Paracrine Communication; Pericardial Effusion; Radioimmunoassay; Systole; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

We have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the development of strokes in rats of a F2 hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats.. To investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.. In view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolated rings of aortas and internal carotid arteries obtained from stroke-prone and stroke-resistant spontaneously hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex-matched Wistar-Kyoto rats was also studied.. Systolic blood pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar-Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular diet were comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar.. The vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Carotid Artery, Internal; Cerebrovascular Disorders; Cyclic GMP; Hypertension; In Vitro Techniques; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitroglycerin; Phenotype; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasodilation

The increase in natriuretic peptides (NP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) production and release by cardiocytes that occurs in hypertension has been considered to be a compensatory mechanism against ventricular overload. Studies on NP production in the spontaneously hypertensive rat (SHR), an experimental model of human hypertension, have produced controversial results and were carried out when hypertension was already established (> 17 weeks). At this time, age-related physiologic and molecular changes in cardiac muscle are difficult to separate from those related to hypertension, ie, increased ANF production and plasma levels. In addition, most of the studies used male rats because the rate of increase in arterial blood pressure--as well as the level to which it rises--is greater in males than in females. Studies of a similar nature using female SHR are not available. The aim of this work was to determine 1) whether ANF and BNP production and secretion increase with the development of hypertension in genetically hypertensive rats; 2) whether a sexual dimorphism in ANF and BNP production and secretion is present in the genetically hypertensive rat during the development of hypertension; and 3) whether the demand for ANF and BNP is the same from each chamber of the heart under these experimental conditions. Age-matched male and female SHR, Wistar-Kyoto (WKY), and Sprague Dawley (SD) rats at 2, 4, and 8 weeks of age were used. The normotensive SD were included to provide a wider basis for baseline findings, as WKY rats are not always a suitable control for SHR due to genetic variations. Natriuretic peptide plasma levels and tissue content were measured by radioimmunoassay. ANF, BNP, as well as alpha- and beta-myosin heavy chain (MHC) mRNA were estimated by Northern blot analysis. Blood pressure (BP) of more than 150 mm Hg was found only in 8-week-old male SHR. Plasma immunoreactive (ir)ANF and irBNP increased significantly at puberty (8 weeks) in both male and female SHR. The earliest molecular change encountered during the development of hypertension was a significant increase in BNP mRNA in the right and left atria from both male and female 8-week-old SHR. In the ventricles from both male and female SHR, there was no increase in the ratio of left ventricular wet weight/body weight, no increase in ventricular ANF mRNA transcripts, and no myosin heavy chain isoform switch (a protein marker of hypertrophy). irBNP ventri

Topics: Age Factors; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Gene Expression; Heart Ventricles; Hypertension; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Sex Factors

The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives.. We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects.. Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups.. Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Circadian Rhythm; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides

The levels of adrenomedullin (ADM), a newly discovered vasodilating and natriuretic peptide, are elevated in plasma and ventricular myocardium in human congestive heart failure suggesting that cardiac synthesis may contribute to the plasma concentrations of ADM. To examine the time course of induction and mechanisms regulating cardiac ADM gene expression, we determined the effect of acute and short-term cardiac overload on ventricular ADM mRNA and immunoreactive ADM (ir-ADM) levels in conscious rats. Acute pressure overload was produced by infusion of arginine8-vasopressin (AVP, 0.05 microg/kg/min, i.v.) for 2 h into 12-week-old hypertensive TGR(mREN-2)27 rats and normotensive Sprague-Dawley (SD) rats. Hypertension and marked left ventricular hypertrophy were associated with 2.2-times higher ir-ADM levels in the left ventricular epicardial layer (178 +/- 36 vs. 81 +/- 23 fmol/g, P<0.05) and 2.6-times higher ir-ADM levels in the left ventricular endocardial layer (213 +/- 23 vs. 83 +/- 22 fmol/g, P<0.01). The infusion of AVP for 2 h in normotensive rats produced rapid increases in the levels of left ventricular ADM mRNA (epicardial layer: 1.6-fold, P<0.05) and ir-ADM (endocardial layer: from 83 +/- 22 to 140 +/- 12 fmol/g, P<0.05), whereas ventricular ADM mRNA and ir-ADM levels did not change significantly in hypertensive rats. Short-term cardiac overload, induced by administration of angiotensin II (33.3 microg/kg/h, s.c., osmotic minipumps) for two weeks in normotensive SD rats resulted in left ventricular hypertrophy (3.05 +/- 0.17 vs. 2.75 +/- 0.3 mg/g, P<0.05) and a 1.5-fold increase (P<0.05) in ventricular ADM mRNA levels. In conclusion, the present results show that pressure overload acutely stimulated ventricular ADM gene expression in conscious normotensive rats suggesting a potential beneficial role for endogenous ADM production in the heart against cardiac overload. Since pressure overload-induced increase in ADM synthesis was attenuated in hypertensive rats, alterations in the ADM system may contribute to the pathogenesis of hypertension in the TGR(mREN-2)27 rat.

Topics: Adrenomedullin; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Heart; Heart Failure; Heart Ventricles; Humans; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Biosynthesis; Peptides; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; RNA, Messenger; Time Factors; Transcription, Genetic

The present study was aimed to investigate the regulatory mechanisms of BNP release. Effects of acute and chronic perturbations in body fluid balance, changes in BP, and regulatory roles of NO and endothelin systems on BNP release were examined in rats. Although acute extracellular volume expansion did not have significant effects on plasma BNP, prolonged high-salt intake increased plasma BNP levels. Plasma BNP levels were also higher in 2K1C rats compared with the control. Although infusion of L-NAME increased the plasma BNP in control, it did not further affect the plasma BNP in rats with high-salt intake. Although L-arginine (20 mg.kg-1 per min) per se did not have significant effects on plasma BNP, it blocked the stimulatory effect of L-NAME (200 micrograms.kg-1 per min). Plasma BNP was severalfold increased following a single injection of endothelin (0.3 micrograms/kg) in normal and high-salt intake groups, the magnitude of which was not significantly affected by the high-salt intake. Although indomethacin did not have significant effects on plasma BNP in normal rats, it blocked the stimulatory effect of 2K1C hypertension. It is concluded that BNP is regulated by chronic changes in body fluid balance and blood pressure. It is also suggested that endothelin and NO systems may directly regulate the secretion of BNP in vivo. An endogenous prostaglandin synthesis may be involved in the stimulated release of BNP in hypertension.

Topics: Animals; Body Fluids; Endothelins; Hypertension; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitric Oxide; Rats; Rats, Sprague-Dawley; Salts; Vasoconstrictor Agents

Chronic pressure overload is known to increase cardiac mass and expression levels of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs. Although mechanical stretching of cardiac myocytes could cause these changes, humoral factor(s) secondary to pressure overload may also be involved. To dissociate humoral effects from the effects of mechanical loading on cardiac hypertrophic responses, we examined expression of ANP and BNP at both mRNA and protein levels and proportions of myosin isoforms in transplanted cervical hearts that were mechanically unloaded under conditions with or without hypertension by aortic coarctation. Seven days after transplantation, cardiac atrophy that usually occurs in transplanted hearts without hypertension by coarctation was prevented in the transplanted hearts with hypertension by coarctation. The levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts with relative to those without hypertension by coarctation. The plasma level of angiotensin II was higher in rats with than without hypertension by coarctation. Plasma endothelin-1 levels were not significantly different between the two groups. In addition, levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts without hypertension relative to those in the in situ hearts. The proportion of the V3 myosin isoform was also increased in the transplanted hearts without hypertension relative to the in situ hearts. These results indicate that humoral factor(s) secondary to the pressure overload produced by aortic coarctation enhanced the cardiac hypertrophic response and elevated the levels of mRNAs encoding these embryonic markers. Moreover, our findings regarding ANP and BNP expression in the transplanted hearts provide additional evidence that the fetal genes are reexpressed during the process of cardiac atrophy as well as in cardiac hypertrophy.

Topics: Angiotensin II; Animals; Aortic Coarctation; Atrial Natriuretic Factor; Atrophy; Blood Pressure; Body Weight; Cardiomegaly; Endothelin-1; Heart Rate; Heart Transplantation; Hypertension; Male; Myosins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Lew; RNA, Messenger; Transcription, Genetic; Transplantation, Heterotopic; Transplantation, Isogeneic

To investigate the activation of particulate guanylate cyclase in pregnant women with pregnancy-induced hypertension (PIH), plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and guanosine 3',5'-cyclic phosphate (cGMP) were measured by radioimmunoassays specific to each substance. Ten normal nonpregnant women, and 30 normal pregnant women, 17 pregnant women with mild PIH and 11 pregnant women with severe PIH in the third trimester were included in this retrospective observational study. The diagnosis and classification of hypertension were carried out according to the technical bulletin (No. 91) of the American College of Obstetricians and Gynecologists. In the pregnant women with mild PIH, plasma cGMP levels as well as ANP and BNP levels were significantly (P < 0.05) higher than those in gestational age-matched normal pregnant or nonpregnant women. But in the pregnant women with severe PIH, plasma cGMP levels were significantly lower than those in pregnant women with mild PIH (P < 0.05), although plasma ANP and BNP levels were higher than those in pregnant women with mild PIH.

Topics: Adult; Atrial Natriuretic Factor; Cyclic GMP; Female; Gestational Age; Humans; Hypertension; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pregnancy; Pregnancy Complications, Cardiovascular; Radioimmunoassay; Retrospective Studies

A genetic model of salt-resistant hypertension has been developed recently through disruption of the guanylyl cyclase-A (GC-A) natriuretic peptide receptor gene (Lopez, M. J., Wong, S. K., Kishimoto, I., Dubois, S., Mach, V., Friesen, J., Garbers, D. L., and Beuve, A. (1995) Nature 378, 65-68). These genetically altered mice were used to determine which of the natural peptides with natriuretic peptide-like structures regulate blood pressure through the GC-A receptor. Atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed precontracted aortic rings in wild-type mice at about 24 nM, but failed to relax such aortas in GC-A null mice, even at micromolar concentrations. C-type natriuretic peptide (CNP), in contrast, caused half-maximal relaxation at concentrations of 335 and 146 nM in aortas from either wild-type or null mice, respectively, suggesting that this peptide acted through a receptor other than GC-A. Since the in vitro results with aortic smooth muscle do not necessarily reflect the physiology of the smaller blood vessels important in blood pressure regulation, the blood pressures of conscious mice infused with the various peptides were determined. ANP caused decreases in blood pressure when infused at rates of 500 ng/kg/min, a rate which resulted in a plasma concentration of 0.8 nM. In the null mice, in contrast, ANP failed to lower blood pressure even at infusion rates of 50 microg/kg/min. Much higher infusion rates for CNP (50 microg/kg/min), which yielded final plasma concentrations of 18.3 nM, were required to lower blood pressure in wild-type mice, but the effects of CNP were not altered in GC-A null mice. Thus, two natriuretic peptides (ANP, BNP) act through GC-A whereas another (CNP) acts through another receptor to regulate blood pressure.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Guanylate Cyclase; Hypertension; In Vitro Techniques; Mice; Mice, Mutant Strains; Muscle Relaxation; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Proteins; Receptors, Atrial Natriuretic Factor; Signal Transduction

A new, fast and reliable radioimmunoassay for measurement of brain natriuretic peptide (BNP) in human plasma has been developed and its application is reported in healthy subjects and in patients with congestive heart failure, chronic renal failure, liver cirrhosis and essential hypertension. The antibody was raised in rabbits, the tracer was made by the iodogen method and polyethylene glycol was used for separation of free and bound tracer. BNP was extracted from plasma using Sep-Pak C18 cartridges. The recovery of unlabelled BNP added to plasma was 77.5 +/- 6.2% (mean +/- SD). The detection limit in plasma was 0.55 pmol l-1. No cross-reactivity existed with the natriuretic peptides ANP, CNP or urodilatin. In 124 healthy subjects the mean BNP was 1.8 +/- 1.0 pmol l-1 (SD), range 0.6-5.5. BNP increased slightly with age, was higher in women than men and had no circadian rhythm. In eight patients with congestive heart failure the median BNP level was 30.5 pmol l-1, range 3.9-65.3. In 14 patients with chronic renal failure the median BNP level was 50.5 pmol l-1, range 10.9-219.8 before dialysis, and 38.0 pmol l-1, range 9.4-180.0 immediately following dialysis. In 25 patients with liver cirrhosis the median BNP value was 7.8 pmol l-1, range 1.2-43.1. There was no difference between patients with or without ascites. In 18 medically treated patients with essential hypertension the median BNP level was 5.0 pmol l-1, range 1.2-45.5 pmol l-1.

Topics: Adult; Aged; Aging; Chromatography, High Pressure Liquid; Circadian Rhythm; Female; Heart Failure; Humans; Hypertension; Iodine Radioisotopes; Isotope Labeling; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Radioimmunoassay; Reference Values; Sensitivity and Specificity; Sex Characteristics

Human brain natriuretic peptide-32 (BNP) (i.e. proBNP(77-108)), the mature form of BNP and secreted predominantly by the cardiac ventricle, is formed from a high molecular weight precursor, proBNP(1-108). We have recently identified the aminoterminal form proBNP(1-76) (NT-proBNP) in human plasma but its source, metabolism and production in circulatory disorders are unknown. We have investigated the relationship between immunoreactive (IR) NT-proBNP and BNP-32 in normal and hypertensive subjects and in patients with cardiac impairment, as well as the regional plasma concentrations in patients undergoing routine cardiac catheterization.. Plasma hormone measurements were made in 26 normal subjects, 20 subjects with untreated mild hypertension and 111 treated patients with a history of coronary heart disease and documented cardiac impairment (left ventricular election fraction (LVEF) < 45% (mean 29%); 25 NYHA Class I, 65 Class II and 21 Class III). Regional blood sampling from the femoral artery, femoral vein, renal vein and coronary sinus was undertaken in 14 patients presenting for left and right cardiac catheterization studies in the course of standard investigation for a range of cardiac disorders.. Plasma samples were assayed for IR NT-proBNP and IR BNP-32 (and atrial natriuretic peptide (ANP) in the regional blood samples). In the patients with cardiac impairment, LVEF was determined by gated radionuclide ventriculography, exercise capacity was measured using a modified Naughton multistage protocol and creatinine clearance was calculated from plasma creatinine, age and weight. In the regional study, extraction ratios across the kidney and lower limb (and step-ups across the heart) were calculated from plasma peptide concentrations.. In normal subjects mean IR NT-proBNP levels (10.8 +/- 1.3 pmol/L) were similar to levels of IR BNP-32 (9.7 +/- 0.5 pmol/L). In hypertensive patients the levels of IR NT-proBNP and IR BNP-32 tended to be higher than but were not significantly different from normal subjects. Both IR NT-proBNP and IR BNP-32 were raised in NYHA Classes I, II and III compared with normals (P < 0.001 for all) with higher levels of both BNP forms seen with increasing cardiac impairment. The levels of IR NT-proBNP were greater than IR BNP-32 in all NYHA Classes (P < 0.001) for all). Overall, the levels of IR NT-proBNP (129 +/- 12 pmol/L) were 4-fold higher than concomitant BNP-32 levels (29 +/- 2 pmol/L). Multivariate analysis showed that LVEF, exercise test time and creatinine clearance were independent predictors of IR NT-proBNP. In all study groups, the levels of IR NT-proBNP and IR BNP-32 levels were highly correlated. Regional plasma sampling showed similar step-ups in IR NT-proBNP and IR BNP-32 levels across the heart, together with similar extraction of both BNP forms across the kidney and lower limb. For both BNP forms, these changes across tissues were significantly less than for ANP.. Plasma levels of immunoreactive amino terminal-proBNP are raised in cardiac impairment, including NYHA Class I, and rise with increasing cardiac decompensation. Metabolism and tissue uptake of immunoreactive amino terminal-proBNP and immunoreactive BNP-32 appear similar. In cardiac impairment the proportional and absolute increment above normal levels of the aminoterminal BNP peptide exceeds that for BNP-32 and suggest that amino terminal-proBNP may be a more discerning marker of early cardiac dysfunction than BNP-32.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiac Catheterization; Coronary Disease; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Reference Values; Regression Analysis; Statistics, Nonparametric; Ventricular Dysfunction, Left

1. The plasma brain natriuretic peptide (BNP) concentration is elevated in patients with essential hypertension and normal systolic function. This may be related to left ventricular hypertrophy or diastolic dysfunction, both of which commonly occur in hypertension. 2. Echocardiography was performed on 32 patients with newly diagnosed untreated mild-to-moderate hypertension (19 men, 13 women; mean +/- SD age 51 +/- 15 years; diastolic blood pressure 99 +/- 12 mmHg; systolic blood pressure 153.2 +/- 18.0 mmHg; plasma creatinine 86 +/- 15 mumol/L; creatinine clearance 92.2 +/- 20.5 mL/min; left ventricular mass index 116 +/- 28 g/m2; left ventricular ejection fraction 66 +/- 9%). A 15 mL peripheral venous blood sample was obtained at the time of echocardiography for radioimmunoassay of BNP. 3. Sixteen patients had abnormal Doppler transmittal flow (E/A ratio < 1) and a higher median plasma BNP concentration compared with those patients with E/A > or = 1 (12.9 vs 5.9 pmol/L, respectively; P = 0.006). The plasma BNP level correlated significantly with E/A ratio (r = -0.50; P = 0.035). Multivariate analysis showed that the E/A ratio is related to plasma BNP, independent of age and blood pressure. 4. Our results suggest that the plasma BNP level is influenced by diastolic dysfunction. Further studies are needed to determine whether assay of plasma BNP helps to identify patients with diastolic dysfunction.

Topics: Adult; Aged; Diastole; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Ventricular Function, Left

In hypertension with cardiac hypertrophy, the specific contributions to increased production of the cardiac natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) by load and the hypertrophic process are not known. In the present work we determine ANF and BNP synthesis and secretion in the aortic-banded rat treated with dosage schedules of the ACE inhibitor ramipril that result in the prevention or regression of both hypertension and hypertrophy (high dosage) or in the prevention or regression of hypertrophy alone with persistent hypertension (low dosage). Myosin heavy chain (MHC) isoform switch was studied as an indicator of ventricular cardiocyte hypertrophy as well as the levels of collagen III mRNA as a measure of changes in extracellular matrix.. Ramipril was administered for 6 weeks just after suprarenal aortic banding, or rats were banded for 6 weeks, after which ramipril was administered during the following 6 weeks. Banding caused an increase in blood pressure, left ventricular weight-to-body weight ratio, plasma and ventricular NP, ventricular NP mRNA, collagen III, and beta-MHC mRNA. Ramipril at 1 mg/kg normalized all these parameters while ramipril at 10 micrograms/kg normalized left ventricular weight-to-body weight ratio but not blood pressure. Plasma and ventricular NP content and mRNA levels were partially normalized by ramipril (10 micrograms/kg). Ramipril (10 micrograms/kg) prevented increased collagen III mRNA levels but did not affect beta-MHC mRNA levels.. (1) NP production and secretion in aortic-banded rats are independently related to increased blood pressure and hypertrophy. (2) A load-dependent component is more important than a load-independent component in regulating left ventricular NP production. (3) ANF production is more sensitive than BNP production to the load-independent component. (4) Low-dose ramipril treatment reverses hypertrophy and the increased collagen III expression but does not reverse the increased beta-MHC isoform expression, suggesting that these are independently regulated processes. (5) Aortic banding and ACE inhibition do not affect atrial NP production and content.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aorta; Atrial Natriuretic Factor; Base Sequence; Body Weight; Constriction; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Organ Size; Ramipril; Rats; Rats, Sprague-Dawley; Renin

Previous studies have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in essential hypertension. However, whether left ventricular geometry affects plasma ANP and BNP levels remains unknown. To investigate the effect of left ventricular geometry on plasma ANP and BNP levels in essential hypertension, we measured plasma ANP and BNP levels in 90 patients with essential hypertension. All patients were hospitalized, and fasting blood samples were obtained in the early morning after 30 minutes of bed rest. Plasma ANP and BNP levels were measured by immunoradiometric assay. Hypertensive patients were classified into four groups according to echocardiographic findings that showed normal geometry, concentric remodeling, eccentric hypertrophy, or concentric hypertrophy. Mean plasma ANP and BNP levels in all essential hypertensive patients were higher than those in age-matched normotensive control subjects. Plasma ANP levels in hypertensive patients with concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were higher than in normotensive control subjects, although there were no differences between normotensive subjects and hypertensive patients with normal geometry. Plasma BNP levels tended to be higher in hypertensive patients with normal geometry, concentric remodeling, and eccentric hypertrophy than in normotensive control subjects; however, the differences were not significant. Plasma BNP levels and BNP/ANP ratio were specifically higher in concentric hypertrophy. There were significant correlations between ANP and left ventricular mass index, relative wall thickness, interventricular septal thickness, posterior wall thickness, and mean arterial pressure. Plasma BNP levels significantly correlated with relative wall thickness, interventricular septal thickness, posterior wall thickness, and left ventricular mass index but not with mean arterial pressure. In addition, plasma BNP levels were well correlated with ANP levels, and the slope for the linear regression model was steeper in concentric hypertrophy than in the other four groups. These results show that plasma ANP and BNP levels are increased in essential hypertensive patients with left ventricular hypertrophy. Furthermore, BNP secretion is augmented to a greater extent in concentric hypertrophy. Thus, measurement of plasma ANP and BNP levels may be useful for the detection of concentric left ventricular hypertrophy in pati

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Prognosis; Regression Analysis

Cardiac ventricle is shown to be an important source of circulating brain natriuretic peptide (BNP) in hypertensive rats with left ventricular hypertrophy (LVH). This study examined the effect of short-term exercise with a bicycle ergometer on plasma BNP concentrations in 21 essential hypertension patients with LVH established by echocardiography. The results were compared with those from 24 age-matched hypertensives without LVH. Blood pressure, heart rate, plasma renin activity (PRA), and plasma norepinephrine level increased during exercise, but the mean increases of these parameters were not different in the two groups. Resting BNP levels were slightly but significantly higher in the LVH group than in the non-LVH group. This peptide increased during exercise in the two groups, but the exercise-induced increase (percent increase) in plasma BNP was significantly greater in the LVH group than in the non-LVH group (207% +/- 50% v 141% +/- 36%, P < .05). The exercise-induced increase in BNP was significantly correlated with the left ventricular (LV) mass index (N = 45, r = .60, P < .01). By contrast, the exercise-induced increase in BNP was not correlated with the exercise-induced increase in heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, PRA, or noradrenaline level. These results suggest that short-term exercise induces an accelerated increase of plasma BNP in hypertensive subjects with LVH. The LV mass appeared to be related to the observed increase of plasma BNP concentration, at least in our hypertensive patients with LVH.

Topics: Adult; Aged; Atrial Natriuretic Factor; Exercise; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renin

Topics: False Positive Reactions; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

The influence of neutral endopeptidase (NEP) inhibition with (S)-thiorphan on the hormonal, renal, and blood-pressure-lowering effects of an infusion of atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) was evaluated in hypertensive transgenic rats (TGR) harboring an additional mouse renin gene (TGR(m(Ren2)27)). These TGR possess an activated natriuretic peptide system as compared with Sprague-Dawley rats (SDR), used in this study as control. (S)-Thiorphan significantly decreased blood pressure in anesthetized TGR but not in anesthetized SDR during the 60-min infusion period. Exogenously administered ANP decreased blood pressure in SDR with no significant effects in TGR after 60 min. In contrast, BNP infusion significantly decreased blood pressure in TGR, while changes in SDR were not significant. The blood pressure was further decreased after combined infusion of ANP and BNP with (S)-thiorphan in TGR. No effect on blood pressure was registered during infusion of CNP in either experimental group. The plasma levels of ANP, BNP, and cGMP were higher in TGR than in SDR, whereas plasma renin activity was lower. Co-administration of ANP, BNP, or CNP with the NEP inhibitor (S)-thiorphan potentiated the plasma ANP, BNP, and cGMP. Infusion of ANP alone did not affect BNP plasma levels of TGR and vice versa. In contrast, CNP infusion increased ANP plasma levels in both TGR and SDR. Renal excretion of sodium and cGMP increased after infusion of (S)-thiorphan and ANP or BNP in both TGR and SDR. The combination of ANP and (S)-thiorphan had a slightly greater effect on urinary excretion of sodium and cGMP in TGR than either compound alone, but the effects were more pronounced in SDR than in TGR. Finally, infusion of CNP alone and in combination with (S)-thiorphan influenced the excretion of sodium and cyclic GMP only slightly. These results indicate that inhibition of neutral endopeptidase by (S)-thiorphan potentiates the hemodynamic and renal effects of natriuretic peptides ANP and BNP, and to some extent those of CNP, in hypertensive TGR and normotensive SDR. In contrast to ANP and BNP, infusion of CNP had no effect on the blood pressure in anesthetized TGR or SDR. Inhibition of NEP therefore seems to be a promising way to potentiate endogenous levels of natriuretic peptides, which may be of therapeutic benefit in cardiovascular diseases such as hypertension or heart failure.

Topics: Animals; Animals, Genetically Modified; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Disease Models, Animal; Drug Therapy, Combination; Electrolytes; Hypertension; Mice; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neprilysin; Protease Inhibitors; Proteins; Rats; Rats, Sprague-Dawley; Renin; Sodium; Thiorphan

We investigated the relationship between changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and changes in cardiac function during mild exercise in patients with mild hypertension. The handgrip test (HGT) was performed by 21 untreated, mildly hypertensive patients, mean age 45 +/- 5 years. M-mode and pulse Doppler echocardiograms were recorded before and during HGT. In 7 patients (Group A), diastolic function, which was determined by the peak early velocity and peak atrial velocity (E/A) ratio using Doppler echocardiography was attenuated during HGT (1.19 +/- 0.21 TO 1.04 +/- 0.16, p < 0.05). There was no change in diastolic function in the remaining 14 patients, left atrial diameter, cardiac index, ejection fraction, plasma renin activity, plasma norepinephrine, blood pressure, nor heart rate were different between the two groups. While ANP was increased in Group A during HGT (from 41.0 +/- 18.2 to 54.0 +/- 24.1 pg/ml, p < 0.05) it was unchanged in Group B (36.8 +/- 16.3 to 33.5 +/- 11.9 pg/ml). BNP did not change in either Group (Group A: 2.9 +/- 3.1 to 3.0 +/- 3.4 pg/ml, Group B: 2.6 +/- 1.6 to 3.6 +/- 4.8 pg/ml). The percent change in ANP during HGT did not correlate with the percent change in BNP. Thus, the impairment of cardiac functional reserve appeared to influence ANP excretion in patients with mild hypertension.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Echocardiography; Exercise; Female; Hand Strength; Heart; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

We examined the relationship between cardiac hypertrophy, myosin heavy chain (MHC) isoform expression, and production of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) before and after the development of DOCA-salt hypertension. DOCA-salt rats exhibited significant left ventricular hypertrophy at the prehypertensive stage (1 week of treatment), without MHC isoform switch or change in natriuretic peptide gene expression. In the hypertensive stage (5 weeks of treatment), pronounced left ventricular hypertrophy was observed, and this was characterized by an increase in beta-MHC protein, resulting in a switch from 90% alpha-MHC to 51% alpha-MHC and 49% beta-MHC. ANF and BNP mRNA levels and peptide content were significantly increased at this stage. Unexpectedly, the MHC isoform switch was evident in the non-hypertrophied right ventricle to the same degree as in the left ventricle. Natriuretic peptide production was also increased in the right ventricle at 5 weeks of treatment, but to a lesser degree than in the left ventricle. In contrast, in the hypertrophied left atrium there was no MHC isoform switch, while ANF and BNP mRNA levels were augmented. Plasma ANF was significantly increased in the prehypertensive stage; this was accompanied by a partial depletion of atrial ANF stores. Plasma BNP was increased only in the hypertensive stage, reflecting an increase in ventricular BNP synthesis and secretion. These results suggest that 1) cardiac hypertrophy, MHC isoform expression, and stimulation of natriuretic peptide production are processes that may be dissociated from each other; 2) increases in plasma ANF without a concomitant increase in plasma BNP reflect atrial hemodynamic overload, while increases in both ANF and BNP in plasma are associated with ventricular hypertrophy; and 3) there exist differences in the storage, secretion, and processing patterns of ANF and BNP in the atria.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Northern; Body Weight; Cardiomegaly; Centrifugation, Density Gradient; Chromatography, High Pressure Liquid; Desoxycorticosterone; Hypertension; Isomerism; Male; Myocardium; Myosin Subfragments; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Organ Size; Radioimmunoassay; Rats; Rats, Sprague-Dawley; RNA; Sodium Chloride

We evaluated the cardiovascular effects of pathophysiological plasma levels of brain natriuretic peptide in seven patients with mild to moderate essential hypertension by performing equilibrium radionuclide angiocardiography at baseline and during brain natriuretic peptide infusion at increasing doses (4, 8, 10, and 12 pmol/kg per minute for 20 minutes each). Brain natriuretic peptide induced a progressive reduction of left ventricular end-diastolic volume (from 107.5 +/- 10.3 to 89.0 +/- 11.0 mL at the end of all infusion periods) and end-systolic volume, whereas stroke volume did not show any significant change (from 64.9 +/- 5.9 to 62.7 +/- 7.8 mL). Cardiac output, arterial pressure, and peripheral vascular resistance did not change significantly. The lack of effects on systemic hemodynamics was probably due to compensatory activation of the sympathetic nervous system, as indicated by the significant increase in plasma norepinephrine levels (from 1.75 +/- 0.18 to 2.19 +/- 0.21 nmol/L), heart rate (from 68 +/- 6 to 81 +/- 6 beats per minute), peak ejection rate, and peak filling rate. These results indicate that brain natriuretic peptide, at the pathophysiological plasma concentrations reached in this study, influences cardiovascular homeostasis mainly by reducing cardiac preload.

Topics: Aged; Female; Hematocrit; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins

1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions. 2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar-Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19-36) 1 mu mol/L prevented HG induced suppression of natriuretic peptides response. 3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.

Topics: Animals; Cells, Cultured; Cyclic GMP; Glucose; Hypertension; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Protein Kinase C; Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Atrial Natriuretic Factor; Receptors, Peptide

To explore the mechanisms of the renal effects of neutral endopeptidase (NEP) inhibition, the effects of an NEP inhibitor, candoxatril (UK 79,300; UK), in Dahl salt-sensitive (SS) and salt-resistant (SR) rats were examined. UK dose-dependently decreased blood pressure (BP) in SS rats (20 mg/kg: 174 +/- 5 vs. 155 +/- 8 mm Hg, p < 0.01) but not in SR rats. Urinary sodium excretion (UNaV) of both rat strains receiving high-salt diets was increased to a greater extent than that of rats receiving low-salt diets. Basal plasma atrial natriuretic peptide (ANP) level in hypertensive SS rats was higher than in SR rats (192 +/- 18 vs. 118 +/- 24 pg/ml, p < 0.05). UK increased ANP levels in the plasma and urine two- and 11-fold, respectively. UK-induced increases in UNaV, urinary cyclic GMP, and plasma ANP concentrations were significantly augmented by coadministration of a clearance receptor agonist, C-ANF(4-23) or brain natriuretic peptide (BNP). Thus, the effects of NEP inhibition appear to be potentiated by the reduced receptor-mediated metabolism of ANP. This may explain the greater response to the NEP inhibitor in Dahl rats with hypertension or high-salt feeding.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Hypertension; Indans; Natriuresis; Natriuretic Peptide, Brain; Neprilysin; Nerve Tissue Proteins; Peptide Fragments; Propionates; Rats; Rats, Inbred Strains; Sodium, Dietary

Vascular remodelling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests the pivotal role of vasoactive substances occurring in the blood vessel, such as angiotensin II (AII), in the control of vascular growth. We recently discovered that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced by vascular endothelial cells and can act as an endothelium-derived relaxing peptide. We also demonstrated gene expression of CNP and the ANP-B receptor, which is one of the three subtypes of the natriuretic peptide receptor and is specific to CNP in blood vessels in vivo. Thus, we propose the existence of a "vascular natriuretic peptide system (NPS)" similar to the vascular renin-angiotensin system (RAS). The present study showed that CNP exerted a growth-inhibitory action and antagonised the growth-promoting action of AII, which was mediated through the AII subtype 1 receptor in cultured vascular smooth muscle cells. In neointimal lesions of rat carotid artery, CNP gene transcript was detectable 2 weeks after balloon injury, and ANP-B receptor gene expression was augmented. These findings suggest that the vascular NPS is activated in proliferative vascular lesions, suppressing further proliferation by antagonising the action of the vascular RAS.

Topics: Angiotensin II; Animals; Arteriosclerosis; Atrial Natriuretic Factor; Base Sequence; Cattle; Cell Division; Cells, Cultured; Endothelium, Vascular; Gene Expression Regulation; Guanylate Cyclase; Hypertension; Male; Molecular Sequence Data; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Atrial Natriuretic Factor; Renin-Angiotensin System; RNA; Stimulation, Chemical

To study the relationship between hypertension and the plasma levels of brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and to determine whether the plasma levels of BNP and CNP are correlated.. A cross-sectional study of the plasma levels of BNP and CNP in hypertensive patients and normotensive controls matched for age and sex was performed.. The hypertension research clinic in a teaching hospital and well-person risk factor screening clinics in general practice health centres.. Fifty-four subjects (29 hypertensive, 25 normotensive controls) took part in the study after giving their informed consent. Hypertensive patients (n = 19) were paired with normotensive controls (n = 19) matched for age and sex to form a subgroup before analysis of the plasma.. The plasma levels of BNP and CNP were determined by specific radioimmunoassays.. The mean plasma concentration of BNP was significantly higher in the hypertensive group than in the paired controls. In contrast, the mean plasma concentration of CNP was not significantly different in the hypertensive group than in the paired controls. Multiple regression analysis of all 54 subjects showed that the plasma level of BNP correlated significantly with age and systolic blood pressure, whereas the plasma level of CNP correlated significantly with sex, heart rate and alcohol intake. The CNP levels did not correlate significantly with either systolic or diastolic blood pressure, or with plasma brain natriuretic levels.. Hypertension is associated with raised BNP but not CNP plasma levels.

Topics: Aging; Blood Pressure; Cross-Sectional Studies; Epinephrine; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Norepinephrine; Proteins; Radioimmunoassay; Reference Values; Sex Characteristics

We have previously reported that C-type natriuretic peptide (CNP), the third member of natriuretic family, was produced in vascular endothelial cells and hypothesized that CNP might be a local regulator of vascular tone and/or growth from endothelial cells. In order to clarify the pathophysiological significance of CNP in humans, we examined the presence of CNP in human circulation and determined plasma levels of CNP in patients with various cardiovascular disorders. The plasma level of CNP in healthy persons was 1.4 +/- 0.6 fmol/ml (n = 13). The plasma level of CNP was markedly increased in patients with septic shock (13.2 +/- 10.1 fmol/ml, n = 11), while there was no alteration in patients with congestive heart failure or hypertension. There was two-fold increase of the plasma CNP level in patients with chronic renal failure. These results indicate that CNP, which can be considered as an endothelium-derived relaxing peptide, is detectable in human circulation and suggest the pathophysiological significance of endothelial CNP in humans.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chromatography, Gel; Chromatography, High Pressure Liquid; Cross Reactions; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Reference Values; Shock, Septic

To evaluate the mechanisms of brain natriuretic peptide (BNP) gene expression, we determined the effect of acute cardiac overload (from 30 min to 4 h) on atrial and ventricular BNP mRNA levels in normal and hypertrophied myocardium. Arginine8 vasopressin (AVP; 0.05 microgram/kg.min) and l-phenylephrine (PHE; 20 micrograms/kg.min) were infused iv to increase cardiac workload in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. At the age of 10-22 months, during the established phase of ventricular hypertrophy, baseline BNP synthesis was increased in the hypertrophic ventricular cells of SHR, as reflected by about 2-fold (P < 0.05-0.001) elevation of levels of immunoreactive BNP (IR-BNP) and BNP mRNA. Intravenous infusions of AVP and PHE increased mean arterial pressure, plasma IR-BNP levels, and ventricular BNP mRNA levels within 1 h of pressure overload; peak levels of BNP mRNA were reached at 4 h. The increase in BNP mRNA levels was slightly greater in the epicardial (2.0- to 2.6-fold; P < 0.01) than in the endocardial layer (1.9- to 2.0-fold; P < 0.01) of the left ventricle. The rapid stimulation of ventricular BNP mRNA synthesis induced by AVP and PHE was accompanied by the simultaneous activation of left atrial BNP gene expression. Left atrial BNP mRNA levels were increased significantly in response to 1-h infusions, and values peaked in both the AVP- and PHE-infused SHR at 2 h, i.e. a 3.6-fold increase in BNP mRNA levels in left atria in AVP-infused SHR, and a 2.5-fold increase in PHE-infused SHR. Right atrial BNP mRNA levels remained unchanged during drug infusion, except for a transient increase in the WKY after 30 min of infusion. The induction of BNP synthesis was also reflected by increased ventricular IR-BNP levels, whereas AVP and PHE did not affect atrial IR-BNP concentrations or contents. In conclusion, the present study shows that pressure overload rapidly stimulates BNP gene expression in the hearts of normal and hypertensive rats. Thus, locally generated BNP in the heart muscle may play a significant role in cardiac adaptation to acute changes in mechanical load.

Topics: Animals; Arginine Vasopressin; Heart Atria; Heart Ventricles; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger

The human heart secretes both atrial natriuretic peptide and brain natriuretic peptide. This study attempts to clarify the pathophysiological significance of the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma brain natriuretic peptide and atrial natriuretic peptide levels in essential hypertension, various secondary hypertension, chronic renal failure, chronic heart failure during cardiac pacing, and acute myocardial infarction were determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively, and increased as a function of age. Plasma brain natriuretic peptide levels showed a larger increase than atrial natriuretic peptide levels in various cardiovascular diseases. In chronic renal failure, whereas plasma atrial natriuretic peptide levels decreased significantly after hemodialysis and were correlated with the changes in body weight, changes in plasma brain natriuretic peptide levels were less prominent and did not show such a correlation. In chronic heart failure, both basal plasma brain natriuretic peptide and atrial natriuretic peptide levels were also significantly elevated. However, in response to acute ventricular or atrial pacing, brain natriuretic peptide levels did not show any increase in contrast to the marked increase of atrial natriuretic peptide levels. In acute myocardial infarction, brain natriuretic peptide levels showed more prominent changes than atrial natriuretic peptide levels and were correlated with serum levels of creatine kinase and cardiac myosin light chain I in most patients. These results suggest that both brain and atrial natriuretic peptides play an important role in the regulation of cardiovascular homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Gland Neoplasms; Adult; Aged; Aging; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiovascular Diseases; Female; Heart Failure; Humans; Hyperaldosteronism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pheochromocytoma; Reference Values; Regression Analysis; Renal Dialysis

1. To examine whether posture-induced changes in central volume affect brain natriuretic peptide secretion, plasma levels of human brain natriuretic peptide-32-like immunoreactivity (hBNP-32-li) were measured by radioimmunoassay in 11 healthy subjects and 20 patients with essential hypertension after 15 min supine, 15 min sitting and 15 min with the legs raised at 60 degrees, together with plasma atrial natriuretic peptide concentration, plasma renin activity and plasma aldosterone concentration. 2. In the supine position, the plasma hBNP-32-li level was 1.57 +/- 0.10 fmol/ml in healthy subjects and significantly higher in hypertensive patients (2.39 +/- 0.13 fmol/ml, P < 0.001). In both groups, plasma hBNP-32-li level significantly (P < 0.001) decreased when sitting (normotensive, 1.22 +/- 0.08 fmol/ml; hypertensive, 1.85 +/- 0.15 fmol/ml, P < 0.001 versus normotensive) and increased again after leg raising (normotensive, 2.13 +/- 0.12 fmol/ml; P < 0.002 versus resting; hypertensive, 2.84 +/- 0.16 fmol/min, P < 0.001 versus resting, P < 0.025 versus normotensive). 3. The plasma atrial natriuretic peptide concentration showed similar behaviour to the plasma hBNP-32-li, whereas plasma renin activity and plasma aldosterone concentration increased during sitting and decreased during leg raising in both healthy subjects and hypertensive patients, who had significantly higher plasma aldosterone levels when supine and sitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Posture; Renin

This study was designed to investigate the modification of plasma and cardiac tissue brain natriuretic peptide concentrations in spontaneously hypertensive rats and Wistar-Kyoto rats in relation to those of atrial natriuretic peptide during the development of hypertension.. Blood pressure, tissue weight, and plasma and cardiac tissue atrial natriuretic peptide and brain natriuretic peptide concentrations were measured in conscious 5, 10, and 18 week old, spontaneously hypertensive, and in corresponding normotensive rats. Pharmacokinetics of atrial natriuretic peptide and brain natriuretic peptide were also examined.. Plasma concentrations of both atrial natriuretic peptide and brain natriuretic peptide in hypertensive rats increased significantly with development of hypertension. The pattern was not in parallel, so that the brain natriuretic peptide/atrial natriuretic peptide ratio was high in spontaneously hypertensive rats. Concentrations of brain natriuretic peptide in the cardiac ventricle were already higher in hypertensive rats than in controls as early as 5 weeks of age, whereas atrial natriuretic peptide concentrations in the ventricle, predominantly in the left ventricles, and the highest brain natriuretic peptide/atrial natriuretic peptide ratio was in the left ventricles from 18 week old spontaneously hypertensive rats. Pharmacokinetics showed that the plasma half lives of atrial natriuretic peptide and brain natriuretic peptide were not different between the two strains.. Although raised blood pressure stimulates both atrial natriuretic peptide and brain natriuretic peptide, production of brain natriuretic peptide in the ventricles is already increased in the prehypertensive stage, and in older hypertensive rats, it is more responsive to progression of hypertension than atrial natriuretic peptide. It is suggested that regulation of production and secretion of the two natriuretic peptides is not temporally coordinated during development of hypertension in this model.

Topics: Animals; Atrial Natriuretic Factor; Half-Life; Hypertension; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY

We have developed a radioimmunoassay for the measurement of immunoreactive BNP (1-32) in human plasma. Simultaneous measurement of ANP have also been carried out to allow for direct comparison between circulating BNP and ANP. Plasma levels of immunoreactive BNP (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in 50 patients with essential hypertension (1.6 +/- 0.2 pmol/l, P < 0.02). Similarly, in patients with essential hypertension plasma levels of ANP were also significantly raised (5.5 +/- 0.6 pmol/l, P < 0.001) when compared with the group of normal healthy subjects (2.8 +/- 0.2 pmol/l). ANP was significantly higher than BNP in normal subjects and in patients with essential hypertension, with ANP/BNP ratios of 2.8 +/- 0.2 and 3.8 +/- 0.3, respectively, in these two groups. A major finding was a significant and positive association between plasma levels of both BNP and ANP within the healthy subjects (r = 0.49, P < 0.05, n = 36) and within the hypertensive subjects (r = 0.76, P < 0.001, n = 50). When all plasma values for BNP and ANP were taken together for both groups, there was an overall correlation coefficient of 0.65 (P < 0.001, n = 86). Both BNP and ANP had significant positive associations with age in hypertensive patients, with correlation coefficients of 0.53 (P < 0.001, n = 50) and of 0.53 (P < 0.001, n = 50) for BNP and ANP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Radioimmunoassay

To explore roles of endogenous atrial natriuretic peptide (ANP) in blood pressure and volume regulation, we examined the effects of a newly developed ANP antagonist, HS-142-1 (HS) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.. We examined 1) the effects of HS on ANP- or brain natriuretic peptide (BNP)-induced reductions in renal vascular resistance (RVR) of rat isolated perfused kidneys, 2) the effects of HS on cyclic GMP (cGMP) production in rat cultured vascular smooth muscle cells pretreated with ANP or BNP, and 3) the renal and systemic effects of HS in DOCA-salt-treated rats and control rats. We found that 1) HS dose-dependently reversed ANP- or BNP-induced decreases in RVR; 2) ANP or BNP at 100 nM caused an eightfold increase in cGMP production. These increases in cGMP were inhibited by HS in a dose-dependent fashion, and 300 micrograms/ml HS decreased cGMP to the control level. HS alone did not influence RVR or cGMP production; and 3) DOCA-salt rats showed higher plasma concentrations of ANP (198 versus 75 pg/ml) and BNP (23.7 versus 2.7 pg/ml, each p < 0.01) than the control rats. Bolus administration of 8 mg/kg HS elevated blood pressure by 8% (p < 0.01). This rise in blood pressure was attributed to an increase in systemic vascular resistance (+14%, p < 0.05). Conversely, urinary excretion of sodium (-41%), glomerular filtration rate (-27%), and plasma (-77%) and urinary cGMP (-69%, each p < 0.01) were decreased by administration of 8 mg/kg HS. These effects were dose dependent in DOCA-salt rats but slight or negligible in the control rats.. These results suggest that endogenous ANP and BNP may be involved in the regulation of blood pressure and body fluid volume in DOCA-salt rats in which ANP and BNP secretion is augmented.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Desoxycorticosterone; Dose-Response Relationship, Drug; Hemodynamics; Hypertension; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polysaccharides; Rats; Receptors, Atrial Natriuretic Factor; Renal Circulation; Sodium Chloride; Vascular Resistance; Vasodilator Agents

Ventricular hypertrophy is characterized by augmentation of the synthesis and storage of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). To evaluate in vitro the cellular mechanisms of immunoreactive ANP (IR-ANP) and BNP (IR-BNP) release from ventricular cardiocytes, we measured the secretory response to graded passive myocardial stretch in isolated atrialectomized perfused hypertrophied hearts of 14- to 18-month-old spontaneously hypertensive rats. At this age, the ventricular levels of both IR-ANP and IR-BNP were markedly higher in spontaneously hypertensive (182 +/- 27 and 32 +/- 3 pmol/ventricle, respectively) than in age-matched normotensive Wistar-Kyoto rats (35 +/- 4 and 12 +/- 1 pmol/ventricle, respectively; P < 0.001), whereas the differences between the strains in atrial levels of these peptides were small. The release of natriuretic peptides from ventricles in response to stretch was examined by increasing the volume of the intraventricular balloon for 10 min. Stretching of the hypertrophied ventricles produced a rapid transient (from 1-5 min) increase in both IR-ANP and IR-BNP secretion. As left ventricular pressure rose from 0 to 26 +/- 1 mm Hg, IR-ANP and IR-BNP release into the perfusion fluid increased 1.8 +/- 0.4- and 2.5 +/- 0.2-fold, respectively. Infusion of staurosporine, known to inhibit protein kinase-C activity in heart cells, blocked the stretch-induced increase in IR-ANP release (F = 3.10; P < 0.001, by analysis of variance), but had no effect on basal ventricular IR-ANP secretion (F = 0.87; P = NS). An L-type calcium channel antagonist, diltiazem, had no significant effect on basal (F = 1.20; P = NS) or stretch-stimulated (F = 1.47; P = NS) IR-ANP release from hypertrophied rat myocardium. Chromatographical analysis revealed that the ventricles primarily release the active processed 28- and 45- amino acid ANP- and BNP-like peptides, respectively, both before and during stretch. This study indicates that stretch stimulates both ANP and BNP secretion from hypertropic ventricular myocytes. The results further suggest that protein kinase-C may be involved in stretch-induced ventricular ANP release, whereas the influx of extracellular calcium may not be necessary.

Topics: Alkaloids; Animals; Atrial Natriuretic Factor; Biomechanical Phenomena; Chromatography, High Pressure Liquid; Heart; Heart Ventricles; Hemodynamics; Hypertension; Kinetics; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Staurosporine

To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension.. We determined the plasma levels of brain and atrial natriuretic peptides in a cross-sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension.. During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P < .05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P < .001).. The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cells, Cultured; Endothelins; Glomerular Mesangium; Humans; Hypertension; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides, Cyclic; Rats

The cardiac natriuretic peptide family includes atrial natriuretic factor and brain or B-type natriuretic peptide, also known as iso-atrial natriuretic factor (isoANF). Although these peptides contribute to cardiovascular homeostasis, their respective roles remain unclear. To study regulation of atrial natriuretic factor and isoANF gene expression during progression of hypertension, we developed a quantitative polymerase chain reaction protocol to measure their transcript level in spontaneously hypertensive rat (SHR) hearts. At the onset of hypertension, atrial natriuretic factor transcripts in 5-week-old SHR were 50% of those of age-matched Wistar-Kyoto (WKY) rats, whereas the level of isoANF transcripts was similar in atria and twofold higher in ventricles. Because atria are the major sites of atrial natriuretic factor gene expression and ventricles contribute predominantly to cardiac isoANF synthesis, total atrial natriuretic factor messenger RNA (mRNA) in the hearts of 5-week-old SHR was about 50% of that in WKY rats, and total isoANF mRNA content was already higher than in control rats. In left ventricles and ventricular septa, progression of hypertension led to a maximal increase of twofold and fourfold in atrial natriuretic factor and isoANF mRNA levels, respectively, with no detectable change in right ventricles. In the atria of older SHR, atrial natriuretic factor and isoANF mRNA levels were comparable to those of age-matched controls. These data indicate that, although increased blood pressure stimulates both atrial natriuretic factor and isoANF gene expression, regulation of the two natriuretic peptide genes is not temporally coordinated in all cardiac compartments. Furthermore, isoANF mRNA is already induced in the ventricles at the onset of the hypertensive stage, and in older SHR, the isoANF gene is hyperresponsive to progression of hypertension compared with atrial natriuretic factor. Thus, isoANF might represent a very sensitive marker of cardiac changes in hypertension.

Topics: Animals; Atrial Natriuretic Factor; Base Sequence; Hypertension; Isomerism; Male; Molecular Probes; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polymerase Chain Reaction; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA; Transcription, Genetic

1. This study examined whether brain and atrial natriuretic peptides (BNP, ANP) are secreted together through the coronary sinus from the heart, and whether plasma concentrations of BNP and ANP were affected by ergometric exercise in patients with essential hypertension. The effects of temocapril, a potent angiotensin-converting enzyme (ACE) inhibitor, on plasma concentrations of these peptides was also examined. 2. The plasma concentrations of immunoreactive (ir) BNP and ir-ANP in the coronary sinus in seven patients with ischaemic heart disease during cardiac catheterization were far greater than values with plasma obtained at the same time from the femoral artery. 3. The plasma concentrations of ir-BNP and ir-ANP increased with exercise and were correlated with each other. Temocapril reduced the blood pressure and slightly (but significantly) decreased the levels of both peptides at rest and during exercise. 4. The results suggest that BNP and ANP were secreted together through the coronary sinus from the heart. The secretion was increased by exercise and suppressed by acute ACE inhibition. The increase in these peptides during exercise may reflect a compensatory mechanism against further elevation of blood pressure.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Coronary Vessels; Exercise; Female; Heart; Heart Rate; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Renin; Rest; Thiazepines

Brain natriuretic peptide (BNP) is secreted through the coronary sinus of the human heart. The purpose of this study was to determine whether BNP secretion from the heart is stimulated by exercise and to examine the relationship between pulmonary arterial BNP concentrations and hemodynamic measurements, especially cardiopulmonary hemodynamics, during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed workloads (25, 50, 75 W) on a bicycle ergometer in the supine position. The mean pulmonary arterial BNP level at rest was 14.8 +/- 4.1 pg/mL, and BNP values gradually increased with higher stages of exercise. At the maximum exercise stage, the BNP value increased to 40.9 +/- 6.5 pg/mL. Close correlations of pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) with pulmonary arterial BNP level were observed at four points at rest and during each stage of exercise. In contrast, heart rate, mean blood pressure, cardiac index (CI), and stroke index (SI) were not correlated with BNP values. Results suggest that cardiac secretion of BNP was increased during exercise in essential hypertensive subjects, and the observed increase of BNP may be related to elevated PAP and PAWP. The enhancement of BNP secretion during exercise in these patients may reflect increased redistribution of blood to the cardiopulmonary compartment.

Topics: Adult; Blood Pressure; Exercise; Exercise Test; Female; Heart; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Artery; Pulmonary Wedge Pressure; Rest; Stroke Volume

A natriuretic peptide, brain natriuretic peptide (BNP), has been isolated from porcine hearts. We performed this study to determine if BNP is secreted from the heart and to identify changes, if any, in the plasma BNP concentration in essential hypertension.. We measured the immunoreactive (ir) BNP concentration at intracardiac sites including the coronary sinus of five patients with heart disease during cardiac catheterization. We examined plasma ir-BNP in 48 hypertensive patients, 15 borderline hypertensive patients, and 25 normotensive subjects.. Plasma ir-BNP in the coronary sinus was greater than at other cardiac sites. The concentration was significantly higher in hypertensive subjects than in borderline hypertensive or normotensive subjects. Hypertensive patients with left ventricular hypertrophy (LVH) established by echocardiography had higher plasma ir-BNP levels than those without LVH. In the hypertensive group, plasma ir-BNP was closely correlated with the LV mass index. In these patients, BNP levels were correlated with mean arterial pressure and inversely correlated with the LV ejection fraction, although these correlations were weak. Reverse-phase high-pressure liquid chromatography showed that the major component of circulating ir-BNP in the hypertensive and normotensive subjects corresponded to authentic human BNP-32.. Human BNP-32 was secreted through the coronary sinus from the heart and may act as a cardiac hormone. Plasma BNP was increased in many of the hypertensive subjects with LVH. The increase in BNP seemed to be related to LVH or the cardiac overload associated with LVH.

Topics: Adult; Cardiac Catheterization; Cardiomegaly; Chromatography, High Pressure Liquid; Clinical Protocols; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Radioimmunoassay

Rat brain natriuretic peptide-45 (rat BNP-45) has recently been isolated from rat heart and shown to be a circulating form of rat BNP. We investigated the effects of rat BNP-45 in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared them with those of rat alpha-atrial natriuretic peptide (alpha-ANP). BNP-45 was a potent natriuretic and hypotensive agent in both strains. The effects were comparable with those of alpha-ANP and were far greater than those of porcine BNP-26 reported previously. In SHR blood pressure decreased more than in WKY following injection of the highest dose (2.0 nmol/kg) of BNP-45 or alpha-ANP. However, WKY were more susceptible than SHR to BNP-45 for diuresis, natriuresis and urinary cGMP excretion. Moreover, a high dose of BNP-45 led to a prolonged lowering of blood pressure and urinary cGMP excretion compared to alpha-ANP, and these features were prominent in WKY. BNP-45 disappeared more slowly than alpha-ANP when the two peptide (2.0 micrograms) were injected i.v. in WKY. Thus, rat BNP-45 and alpha-ANP had comparable hypotensive and natriuretic potency; however, the action and plasma half-life of rat BNP-45 were more prolonged.

Topics: Amino Acid Sequence; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Diuretics; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Urodynamics

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle greater than right ventricle greater than right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.

Topics: Animals; Atrial Natriuretic Factor; Gene Expression; Heart Atria; Heart Ventricles; Hypertension; In Vitro Techniques; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Perfusion; Rats; Rats, Inbred WKY; RNA, Messenger; Secretory Rate

Displacement of bound [125I]alpha-atrial natriuretic peptide (alpha-ANP) by brain natriuretic peptide (BNP) was used to map receptors common to both peptides in rat brain by in vitro autoradiography. Both spontaneously hypertensive rats (SHR) and the normotensive Wistar-Kyoto control strain (WKY) were studied. In both strains, [125I]alpha-ANP bound densely to subfornical organ, choroid plexus and arachnoid mater. Binding at these sites in either strain was displaced similarly by 1 microM unlabelled alpha-ANP or BNP. However, no [125I]alpha-ANP was displaced by peptides unrelated to alpha-ANP or BNP. In WKY, both alpha-ANP and BNP competed with similarly high affinities for binding sites occupied by [125I]alpha-ANP. This was also true for SHR. However, SHR showed a substantial reduction in the maximum number of binding sites in the subfornical organ and choroid plexus which were competed for by the peptides. Therefore, BNP may be a significant high affinity ligand for brain receptors previously thought specific for atrial natriuretic peptides, including receptors which vary between WKY and SHR.

Topics: Animals; Atrial Natriuretic Factor; Brain; Hypertension; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred Strains

Four experimental groups of rats treated with (1) DOCA-salt, (2) DOCA or (3) salt, and (4) controls were used to study the participation of brain natriuretic peptide (BNP) in the development of hypertension. Plasma and cardiac tissue concentrations of BNP as well as atrial natriuretic peptide (ANP) were measured in each group by using radioimmunoassays specific to rat BNP or ANP. Plasma BNP levels in DOCA-salt hypertensive group were higher than those in control (p less than 0.01), salt (p less than 0.01) and DOCA (p less than 0.01) groups. A positive correlation was observed between plasma BNP levels and blood pressure (r = 0.70, p less than 0.001) and between plasma ANP levels and blood pressure (r = 0.62, p less than 0.001). Plasma BNP/ANP ratio increased parallel with elevation of blood pressure. Plasma BNP levels correlated negatively with atrial BNP concentration (r = -0.33, p less than 0.05), but positively with ventricular BNP (r = 0.76, p less than 0.001). Compared with controls, tissue BNP-45/gamma-BNP ratio in the DOCA-salt rats was lower in atrium, but higher in ventricle. Thus, in DOCA-salt hypertension atrial BNP decreased with exhaustion of stored BNP-45, while ventricular BNP increased as BNP-45 accumulated. These results suggest that BNP is a novel cardiac hormone, synthesized, processed and secreted in response to changes in blood pressure. BNP may play different roles in controlling blood pressure than those assumed by ANP.

Topics: Animals; Atrial Natriuretic Factor; Chromatography, Gel; Desoxycorticosterone; Heart Atria; Heart Ventricles; Hypertension; Immunoglobulin G; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Strains

Effects of four doses (0.1, 0.2, 1.0 and 2.0 nmol/kg) of brain natriuretic peptide (BNP) on natriuresis and blood pressure were investigated in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An intravenous injection of 1.0 and 2.0 nmol/kg of BNP caused a significant increase of natriuresis and reduction of blood pressure in SHR and WKY. These effects were essentially identical to the effects of atrial natriuretic peptide (ANP). Remarkable bioactivity elicited by BNP rasises the possibility that BNP has a role in the regulation of blood pressure and water-electrolyte balance. On the other hand, when the effects of BNP on both strains of rats were compared with those of alpha-human ANP reported previously, the hypotensive effect of BNP was less than those of alpha-human ANP only in SHR. It is suggested that BNP might have different bioactivity than that of ANP in SHR.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Hypertension; Kinetics; Natriuresis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Urine

1. Both natriuretic and hypotensive effects of brain natriuretic peptide (BNP), a novel peptide identified in porcine brain, were investigated in anaesthetized DOCA-salt rats and control rats. 2. An intravenous injection of two different doses (0.5 and 5.0 nmol/kg) of BNP produced a rapid and marked natriuresis and hypotension in DOCA-salt rats. 3. In particular, significant differences of responsiveness were observed between DOCA-salt and control rats when administered the lower dose of BNP. 4. It was suggested that DOCA-salt rats might be relatively more susceptible to BNP.

Topics: Anesthesia; Animals; Blood Pressure; Desoxycorticosterone; Hypertension; Male; Natriuresis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Strains