natriuretic-peptide--brain and Obesity

Although the prevalence of heart failure has been increasing over time, the presentation of heart failure has been shifting, with a greater proportion of preserved ejection fraction and more slowly progressive symptoms that require recognition in the outpatient setting. These shifts have placed more of the diagnostic responsibility onto primary care physicians, who often are challenged to determine the etiology of common symptoms in patients who often have several other potential reasons for these symptoms. Establishing a diagnosis of heart failure requires a step-wise approach that includes physical exam (looking for multiple signs of hypervolemia), labs (B-type natriuretic peptide levels), and echocardiography (structural and functional measures). Diagnostic algorithms are particularly challenging in patients with obesity, which limits the assessment of intravascular volume on exam, the quality of cardiac imaging, and the diagnostic accuracy of B-type natriuretic peptide levels, which may be falsely low. In these challenging patients, the use of risk scores, invasive testing of intravascular volume, or empiric treatment of hypervolemia may be needed to determine whether symptoms are due to heart failure. Once a diagnosis of heart failure is established, several treatments can be beneficial, from diuretics to relieve congestion to various aspects of guideline-directed medical therapy, some of which vary according to the ejection fraction of the patient. In addition, a diagnosis of heart failure may alter the treatment plan for comorbidities, including selection of anti-hypertensive and glucose-lowering medications, and medical or surgical treatments for obesity. While a diagnosis of heart failure may be challenging in many patients with slowly progressive and non-specific symptoms, early recognition and treatment can be extremely effective at preventing hospitalizations, prolonging survival, and improving quality of life.

Topics: Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Quality of Life; Stroke Volume

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

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

The results of several recent experimental studies using animal models and clinical trials suggested that obesity is not merely an epiphenomenon or a prominent comorbidity in patients with heart failure (HF). Indeed, recent studies suggest that obesity is intimately involved in the pathogenesis of HF with preserved ejection fraction (HFpEF). The most recent studies indicate that approximately 50% of HF patients have HFpEF. As standard pharmacological treatment usually shows only a weak or even neutral effect on primary outcomes in patients with HFpEF, treatment strategies targeted to specific groups of HFpEF patients, such as those with obesity, may increase the likelihood of reaching substantial clinical benefit. Considering the well-known inverse relationship between body mass index (BMI) values and B-type natriuretic peptide (BNP) levels, it is theoretically conceivable that the measurement of natriuretic peptides, using cutoff values adjusted for age and BMI, should increase diagnostic and prognostic accuracy in HFpEF patients. However, further experimental studies and clinical trials are needed to differentiate and better understand specific mechanisms of the various HFpEF phenotypes, including obese HFpEF.

Topics: Body Mass Index; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Phenotype; Stroke Volume

Cardiac biomarkers play important roles in routine evaluation of cardiac patients. But while these biomarkers can be extremely valuable, none of them should ever be used by themselves-without adding the clinical context. This paper explores the non-cardiac pathologies that can be seen with the cardiac biomarkers most commonly used.. High-sensitivity troponin assay gained FDA approval for use in the USA, and studies demonstrated its diagnostic utility can be extended to patients with renal impairment. Gender-specific cut points may be utilized for high-sensitivity troponin assays. In the realm of the natriuretic peptides, studies demonstrated states of natriuretic peptide deficiency in obesity and in subjects of African-American race. Regardless, BNP and NT-proBNP both retained prognostic utilities across a variety of comorbid conditions. We are rapidly gaining clinical evidence with use of soluble ST2 and procalcitonin levels in management of cardiac disease states. In order to get the most utility from their measurement, one must be aware of non-cardiac pathologies that may affect the levels of biomarkers as although many of these are actually true values, they may not represent the disease we are trying to delineate. A few take-home points are as follows: 1. A biomarker value should never be used without clinical context 2. Serial sampling of biomarkers is often helpful 3. Panels of biomarkers may be valuable.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Renal Insufficiency; Risk Assessment; Risk Factors; Stroke; Troponin

Approximately 50% of patients with symptoms and signs of heart failure have a left ventricular ejection fraction (LVEF) ≥50% and are often simply referred to as 'heart failure with preserved EF', 'HFpEF'. Many of such patients have HF secondary to specific cardiac conditions (i.e., valvular or pericardial disease) in which the symptoms and signs occur despite the LVEF being preserved due to diastolic dysfunction secondary to the underlying disease (secondary HFpEF), differently from those HFpEF patients in which the impaired LV filling is due to a primary diastolic dysfunction (primary HFpEF). When primary HFpEF patients are properly diagnosed, they appear to have a milder form of HF with a lower cardiovascular mortality compared with HFrEF and secondary HFpEF population, but a risk of HF hospitalization that is significantly higher than patients with similar cardiovascular risk factors but without the diagnosis of HFpEF. We herein review the diagnostic approach to HFpEF and present a differential diagnosis of HFpEF in a primary and secondary form.

Topics: Algorithms; Biomarkers; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Heart Failure, Diastolic; Heart Valve Diseases; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pericarditis, Constrictive; Risk Factors; Stroke Volume; Tachycardia

Atrial and B-type Natriuretic Peptides (NP) are cardiac hormones with potent cardiovascular and metabolic effects. They signal through the NPRA/cGMP system and are inactivated by a clearance receptor NPRC and neutral endopeptidases (NEP). Recombinant ANP and BNP are currently used as drug treatment for acute decompensated congestive heart failure. Recent literature indicate that a defective NP system is linked to obesity and predict the risk of type 2 diabetes (T2D). Areas covered: This article reviews recent epidemiological, clinical and preclinical evidences that NP system deficiency may be causal of obesity and T2D. The molecular mechanisms of the NP pathway in several metabolic target tissues are presented. The therapeutic potential of NP in obesity and T2D is discussed. Expert opinion: Targeting the NP pathway may offer a novel therapeutic avenue for the management of obesity and T2D. The benefit/risk of drugs increasing circulating NP levels by blocking NPRC and NEP, and/or enhancing NPRA signaling should be assessed in obese and type 2 diabetic individuals.

Topics: Animals; Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Humans; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Neprilysin; Obesity; Receptors, Atrial Natriuretic Factor

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

Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-type natriuretic peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationship between BNP and NT-proBNP levels and myocardial stiffness is complex. Recent data suggest an inverse relationship between BNP and NT-proBNP levels and body mass index. Given the ever-increasing prevalence of obesity world-wide, it is important to understand the benefits and limitations of HF biomarkers in this population. This review will explore the biology, physiology, and pathophysiology of these peptides and the cardiac endocrine paradox in HF. We also examine the clinical evidence, mechanisms, and plausible biological explanations for the discord between BNP levels and HF in obese patients.

Topics: Biomarkers; Body Mass Index; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Prognosis

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

The aim of this review is to analyze in detail some possible pathophysiological mechanisms linking obesity and cardiac endocrine function, in order to try to explain the negative association previously observed between BMI and BNP values in both healthy subjects and patients with cardiovascular diseases. In particular, we discuss the hypothesis that the response of the cardiac endocrine system is the integrated resultant of several and contrasting physiological and pathological interactions, including the effects of peptide and steroid hormones, cytokines, cardiovascular hemodynamics, clinical conditions, and pharmacological treatment. Several studies suggested that gonadal function regulates both body fat distribution and cardiac endocrine function. Visceral fat expansion can increase the clearance of active natriuretic peptides by means of an increased expression of clearance receptors on adipocytes, and in this way, it may contribute to decrease the activity of the cardiac endocrine system. Moreover, obesity is associated with ectopic lipid deposition even in the heart, which may directly exert a lipotoxic effect on the myocardium by secreting in loco several cytokines and adipokines. Obese subjects are frequently treated for hypertension and coronary artery disease. Pharmacological treatment reduces plasma level of cardiac natriuretic peptides, and this effect may explain almost in part the lower BNP levels of some asymptomatic subjects with increased BMI values. At present time, it is not possible to give a unique and definitive answer to the crucial question concerning the inverse relationship between the amount of visceral fat distribution and BNP levels. Our explanation for these unsatisfactory results is that the cardiac endocrine response is always the integrated resultant of several pathophysiological interactions. However, only few variables can be studied together; as a result, it is not possible to perform a complete evaluation of pathophysiological mechanisms under study. We are still not able to well integrate these multiple information together; therefore, we should learn to do it.

Topics: Body Mass Index; Brain-Derived Neurotrophic Factor; Case-Control Studies; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity

Congestive heart failure is a very real public health issue not only in the United States, but worldwide. Mortality in patients with congestive heart failure is typically either sudden cardiac death or pump failure. Paradoxically, patients with less severe heart failure are at higher relative risk of sudden cardiac death. Defining which patients are best treated with implantable defibrillators and resynchronization is the purpose of this review.

Topics: Biomarkers; Cardiac Resynchronization Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Evidence-Based Medicine; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardial Revascularization; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Stroke Volume

Topics: Ankle Brachial Index; Anti-Obesity Agents; Arteriosclerosis; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Disease; Diabetes Mellitus; Diagnostic Imaging; Dyslipidemias; Endarterectomy; Fibrinolytic Agents; Genetic Markers; Glycated Hemoglobin; Health Behavior; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Life Style; Lipids; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Risk Assessment; Risk Factors; Smoking Cessation; Stents; Stroke; Thrombosis; Troponin I

Preoperative cardiac risk assessment is the cornerstone of rationale perioperative management that guides invasive surgical interventions. In addition to clinical risk factors, a simple screening biomarker would be useful for identifying those surgical patients who might benefit from additional cardiac testing or therapeutic interventions. Preoperative plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are predictors of cardiac events after noncardiac surgery. NT–proBNP is synthesized in the ventricular myocardium in response to ventricular wall stress. To further increase the diagnostic accuracy of NT-proBNP for preoperative screening, it is important to identify confounding factors that influence NT-proBNP levels and their interaction with identifying risks for adverse cardiac events. Moreover, until now the available data from previous studies has been unable to consistently recognize the optimal discriminatory threshold for NT-proBNP. Currently, the ongoing DECREASE-VI study is conducted to evaluate whether current preoperative risk stratification can be improved by incorporating NT-proBNP measurements.

Topics: Age Factors; Anemia; Cardiovascular Diseases; General Surgery; Humans; Intraoperative Complications; Myocardium; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Prognosis; Risk Assessment; Risk Factors; Sex Factors

The objective of this study was to investigate the association between natriuretic peptides, obesity and related comorbidities. A systematic review of the English language literature from 1996 to 2008 was performed with Pubmed/MEDLINE and the ISI Web of Knowledge. 'Natriuretic peptides', 'atrial natriuretic factor', 'brain natriuretic peptide', 'obesity', 'body mass index', 'lipolysis' and 'adipose tissue' were used as Mesh terms. We also conducted a handle search among the references of the original articles selected. Finally, seventy-five studies were considered eligible for inclusion in the review. Natriuretic peptides are widely known as body homeostasis regulators. Recently, their action as lipolytic agents has been identified. Obese patients, especially those with hypertension and metabolic risk factors, have reduced plasma levels of natriuretic peptides. Whether this precedes or follows obesity and its complications remains undefined. The lipolytic effect of natriuretic peptides indicates that they may be involved in the pathophysiology of obesity. In general, studies with obese patients support paradoxical reduced levels of natriuretic peptides. However, the selection of subjects and classification of obesity and heart failure varied among the reviewed studies, rendering comparison unreliable.

Topics: Adipose Tissue; Atrial Natriuretic Factor; Heart Failure; Hemodynamics; Humans; Lipid Metabolism; Lipolysis; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity

Concentrations of both B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) are relatively lower among patients with a higher body mass index (BMI). Based on data at hand, this is probably related to reduced synthesis or secretion of the peptides, rather than increased clearance (which may play only a minor role in this context). Despite this fact, age-adjusted NT-proBNP cut points to "rule in" heart failure (HF) and age-independent cut points to "rule out" HF in patients with acute dyspnea are equally useful for obese and lean patients, and no adjustment of NT-proBNP thresholds for BMI is recommended. Furthermore, the consensus-recommended NT-proBNP cut point of 1,000 ng/L for prognostication in acute dyspnea is equally useful across all BMI categories, without the need for further adjustment for weight. Thus, despite the BMI-related NP handicap observed in overweight and obese patients, NT-proBNP remains powerfully useful for diagnostic and prognostic evaluation across the entire range of BMI values.

Topics: Biomarkers; Body Mass Index; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

Obesity is associated with an increased risk of heart failure. Apparently healthy obese individuals can, however, exhibit subclinical left ventricular dysfunction. The use of myocardial imaging techniques to detect this subclinical change could have important management implications with respect to initiating prophylactic therapy. In this Review, we evaluate possible pharmacologic and nonpharmacologic strategies for treating obesity cardiomyopathy in the context of currently understood mechanisms, including myocardial remodeling and small vessel disease, and more speculative mechanisms such as insulin resistance, and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems.

Topics: Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Ventricular Dysfunction, Left; Weight Loss

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

Natriuretic peptide (NPs) levels have achieved worldwide acceptance. They are excellent rule-in and rule-out biomarkers for patients presenting with dyspnea. In the hospital, NP levels may represent altered forms of B-type natriuretic peptide (BNP), including the inactive precursor molecule, pro-BNP. NP levels drop during hospitalization as the patient is decongested. In the future, NP levels may be used as a surrogate to titrate outpatient therapy.

Topics: Acute Coronary Syndrome; Acute Disease; Algorithms; Biomarkers; Dyspnea; Heart Failure; Humans; Kidney Diseases, Cystic; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism

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

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

Topics: Animals; Atrial Natriuretic Factor; Catecholamines; Fatty Acids, Nonesterified; Humans; Lipolysis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity

Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients.. Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days.. Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Overweight; Pilot Projects; Single-Blind Method

High Protein diets may be associated with endocrine responses that favor improved metabolic outcomes. We studied the response to High Protein (HP) versus High Carbohydrate (HC) Diets in terms of incretin hormones GLP-1 and GIP, the hunger hormone ghrelin and BNP, which is associated with cardiac function. We hypothesized that HP diets induce more pronounced release of glucose lowering hormones, suppress hunger and improve cardiac function.. 24 obese women and men with prediabetes were recruited and randomized to either a High Protein (HP) (n = 12) or High Carbohydrate (HC) (n = 12) diet for 6 months with all food provided. OGTT and MTT were performed and GLP-1, GIP, Ghrelin, BNP, insulin and glucose were measured at baseline and 6 months on the respective diets. Our studies showed that subjects on the HP diet had 100% remission of prediabetes compared to only 33% on the HC diet with similar weight loss. HP diet subjects had a greater increase in (1) OGTT GLP-1 AUC(p = 0.001) and MTT GLP-1 AUC(p = 0.001), (2) OGTT GIP AUC(p = 0.005) and MTT GIP AUC(p = 0.005), and a greater decrease in OGTT ghrelin AUC(p = 0.005) and MTT ghrelin AUC(p = 0.001) and BNP(p = 0.001) compared to the HC diet at 6 months.. This study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for improved insulin sensitivity and β cell function compared to the HC diet. HP ghrelin results demonstrate the HP diet can reduce hunger more effectively than the HC diet. BNP and other CVRF, metabolic parameters and oxidative stress are significantly improved compared to the HC diet. CLINICALTRIALS.. NCT01642849.

Topics: Adult; Appetite Regulation; Biomarkers; Diet, High-Protein; Dietary Carbohydrates; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Heart Disease Risk Factors; Humans; Hunger; Incretins; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prediabetic State; Prospective Studies; Remission Induction; Tennessee; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Topics: Aged; Biomarkers; Body Mass Index; Diuretics; Dose-Response Relationship, Drug; Female; Heart Failure; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Precursors; Stroke Volume

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that presents clinicians with a diagnostic challenge. The use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) level above and below the proposed cut-off.. Stable patients (n = 30) with left ventricular (LV) ejection fraction ≥ 50% were eligible if they had a diagnosis of HF according to the European Society of Cardiology diagnostic criteria. Characteristics of patients with NT-proBNP below (≤125 pg/mL) and above (>125 pg/mL) the diagnostic criterion were compared.. There were 19 (66%) women with median age 54 years. Half were African American (16, 53%), and most were obese. There were no significant differences in clinical characteristics or medication use between groups. LV end-diastolic volume index was greater in high NT-proBNP patients (P = 0.03). Left atrial volume index, E/e' ratio, and E/e' ratio at peak exercise were not significantly different between NT-proBNP groups. Peak oxygen consumption (VO. NT-proBNP was below the proposed diagnostic cut-off point of 125 pg/mL in half of this obese study cohort. Cardiac diastolic dysfunction and cardiorespiratory fitness were not significantly different between high and low NT-proBNP patients. These data indicate that excluding the diagnosis of HFpEF based solely on NT-proBNP levels should be discouraged.

Topics: Aged; Biomarkers; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index; Stroke Volume

The natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production.. We sought to determine the acute effects of insulin administration on natriuretic peptide concentrations.. 31 men and women (11 lean, 10 overweight, and 10 obese), ages 30-70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol).. From baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 μU/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41).. Insulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Heart failure is a common cause of hospitalization and can be divided into types with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). In this subanalysis of the HABIT (Heart Failure Assessment With BNP in the Home) trial, we examined the differences between home B-type natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF and with HFrEF before decompensation.. This was a retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The HFpEF patients compared with HFrEF patients were older and more obese and had lower baseline BNP values. Intra-individual BNP dispersion (spread of distribution over time) was greater in HFpEF than in HFrEF owing to rapid fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF. However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated with an increased risk of acute decompensated heart failure (ADHF; hazard ratio 4.0), whereas a similar association was not observed in HFrEF. Weight gain ≥5 lb in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and HFrEF, whereas a lower threshold of ≥2 lb weight gain over 3 days in patients with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with decompensation (60% sensitivity).. Patients with HFpEF and HFrEF have variations in their BNP and weight before decompensation. The rapid time scale behaves differently between the groups. In those with HFpEF, a 3-day period characterized by ≥2 lb weight gain and/or >200 pg/mL BNP rise was significantly associated with decompensation. Future prospective studies investigating different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients should be performed to fully learn the value of BNP changes before clinical deompensation.

Topics: Aged; Biomarkers; Body Weight; Double-Blind Method; Female; Heart Failure; Home Care Services; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prospective Studies; Retrospective Studies; Stroke Volume; Weight Gain

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Body Mass Index; Chronic Disease; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Obesity; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Protease Inhibitors; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

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

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

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP).. The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887).. At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI.. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

Topics: Adipose Tissue; Adiposity; Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Life Style; Male; Metformin; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Regression Analysis

An inverse relationship between brain natriuretic peptide (BNP) levels and body mass index (BMI) has been described for patients with left ventricular (LV) systolic dysfunction. In this study, the association of BMI, BNP levels and mortality in patients hospitalized for heart failure with preserved LV systolic function (HFpLVF) was investigated.. One hundred fifty consecutive patients (98% men) who were hospitalized with HFpLVF and had BNP levels measured on admission were analyzed. Patients were divided into categories of BMI: normal (BMI < 25 kg/m), overweight (BMI 25-29.9 kg/m) and obese (BMI ≥ 30 kg/m). Relevant clinical and echocardiographic characteristics and all-cause mortality were obtained through chart review.. BNP levels were significantly lower in obese (median = 227 pg/mL) and overweight (median = 396 pg/mL) patients compared with those with normal BMI (median = 608 pg/mL, P = 0.003). Higher BMI predicted BNP levels of <100 pg/mL. Compared with patients with normal BMI, overweight and obese patients had a significantly lower risk of total mortality, even after adjusting for other clinical characteristics, including log-transformed BNP levels, atrial fibrillation, the use of beta-blockers at discharge, age, hemoglobin levels and the presence of pulmonary congestion on admission. Higher BNP levels also independently predicted mortality.. An inverse relationship between BMI and BNP levels exists in patients hospitalized with HFpLVF. Higher BMI is associated with lower mortality, whereas higher BNP levels predict higher mortality in male patients with HFpLVF. These findings should be confirmed in a larger multicenter setting.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Atrial Fibrillation; Body Mass Index; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Retrospective Studies; Ventricular Function, Left

Obesity is associated with left ventricular diastolic dysfunction and altered heart rate variability, as well as pulmonary dysfunction. The relationship between asthma and cardiac dysfunction in severely obese subjects is unknown, although it has been hypothesized that cardiac dysfunction may contribute to increase airway hyper-responsiveness (AHR). This study aimed to determine if AHR is associated with left ventricular diastolic dysfunction and heart rate variability in severely obese subjects.. Sixty-one subjects with severe obesity (BMI ≥35 kg/m2 with comorbidities) completed this study. All subjects completed respiratory questionnaires, spirometry, lung volume measurements, methacholine inhalation test, 24hour Holter monitoring and a complete echocardiography evaluation. Blood samples were obtained for measurement of metabolic markers. Subjects with AHR, defined by a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml, were compared with those with no AHR (PC20 ≥8 mg/ml).. According to these criteria, 32 subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml respectively, p < 0.001). The groups were similar for anthropometric data and comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo-B, C-reactive protein (CRP) and pro-BNP levels were also comparable between groups (p > 0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices of heart rate variability and overall cardiac function were similar in subjects with or without AHR but grade 2 left ventricular diastolic dysfunction was more prevalent in subjects with AHR (p=0.037).. Altered cardiac function, dysglycemia and dyslipidemia do not seem to be significantly associated with AHR in severely obese subjects in contrast to systemic inflammation.

Topics: Adult; Aged; Asthma; Blood Glucose; Bronchoconstrictor Agents; C-Reactive Protein; Female; Heart Diseases; Heart Rate; Humans; Inflammation; Lipids; Male; Methacholine Chloride; Middle Aged; Natriuretic Peptide, Brain; Obesity; Respiratory Function Tests

Atrial natriuretic peptides (ANP) and Brain natriuretic peptides (BNP) stimulate fat cell plasma membrane receptors. They are potent lipolytic agents on isolated fat cells from subcutaneous adipose tissue. The physiological effects of continuous endurance exercise on ANP release and plasma free fatty acids (FFA) concentrations have been well described. The enhancement of fat metabolism using high intensity intermittent exercise protocols has been assessed in more recent investigations. The combined effects of endurance exercise and water immersion on ANP and FFA plasma concentration and the magnitude of excess post-exercise oxygen consumption (EPOC) might be further enhanced by choosing the most effective exercise protocol. Exercise modalities may play a significant role in the future prevention and treatment of obesity.. The two testing trials will be performed according to a randomized and cross-over design. Twenty healthy sedentary pre-obese and obese class-1 men will be scrutinized with regard to their metabolic responses to continuous exercise in water and to high intensity endurance exercise in water. Both trials will be matched for energy expenditure. After preliminary testing, the tests will be conducted as repeated measurements. The two different exercise protocols will be compared. The aims of the study are to investigate (1) whether continuous endurance exercise or high intensity intermittent endurance exercise in water elicits both a higher release of ANP and BNP and a higher plasma concentration of glycerol and (2) to determine whether continuous endurance exercise in water or a high intensity intermittent endurance exercise in water would lead to a more pronounced short term (two hours) EPOC effect.. If our hypothesis would be confirmed, the most effective exercise protocol based on the combined effects of high intensity endurance exercise and water immersion on ANP and BNP release and glycerol plasma concentrations can be identified. Moreover, the magnitude of the EPOC effect can be augmented. Our study would provide a major contribution for creating optimized exercise modalities in the prevention and treatment of obesity.. Current controlled trials, ISRCTN95488515.

Topics: Atrial Natriuretic Factor; Biomarkers; Cross-Over Studies; Exercise Therapy; Fatty Acids, Nonesterified; Glycerol; Humans; Hydrotherapy; Immersion; Male; Natriuretic Peptide, Brain; Obesity; Physical Endurance; Research Design; Sedentary Behavior; Switzerland; Time Factors; Treatment Outcome; Up-Regulation; Water

Look AHEAD (Action for Health in Diabetes) is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with heart failure (HF) risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and 1-year blood samples were assayed for NT-proBNP in a random sample of 1,500 without, and all 628 with, self-reported baseline CVD (cardiovascular disease) (N = 2,128). Linear models were used to assess relationships that log-transformed NT-proBNP had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had with intervention assignment. At baseline, the mean (s.d.) age, BMI, and hemoglobin A(1c) (HbA(1c)) were 59.6 (6.8) years, 36.0 kg/m(2) (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT-proBNP was not different by condition (ILI 53.3 vs. DSE 51.5, P = 0.45), was not associated with BMI, and was inversely associated with HbA(1c). At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%, P = 0.046). The increased NT-proBNP associated with ILI was correlated with changes in HbA(1c), BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an ILI that reduced weight was associated with an increased NT-proBNP.

Topics: Biomarkers; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Predictive Value of Tests; Risk Reduction Behavior; Time Factors; Weight Loss

Adiponectin exerts cardiovascular protective actions, although some studies have shown the opposite. In hemodialysis, obese subjects display lower mortality rates despite hypoadiponectinemia, while higher adiponectin concentrations correlate with an elevated cardiovascular risk in nonobese subjects. The aim of the study is to suggest that adiponectin level variations are associated with differences in the body mass index (BMI). The interplay between adiponectin and pro-brain natriuretic peptide (Pro-BNP) levels may vary according to body fat mass. Fifty-two chronic hemodialysis patients were divided into three groups. Group A, BMI<25 (n=20); Group B, BMI 25 to 30 (n=21), and Group C, BMI>30 (n=11). Diabetics: Group A 10%; Group B 6 29%; Group C 55%, P=0.027. Determinations: Adiponectin, Pro-BNP, insulin, insulin resistance (HOMA), troponin T, nutritional status, ultrafiltration rates, C-reactive protein (CRP), vascular accesses, and echocardiography. Group A: adiponectinemia positively and significantly correlated with Pro-BNP, CRP, and troponin T. As BMI increased, adiponectin, Pro-BNP, and malnutrition significantly decreased, while insulin, HOMA, and ultrafiltration rates significantly increased. Cardiac restriction was significantly higher in obese patients. In all groups, Pro-BNP and troponin T displayed a strong positive correlation. In low-BMI subjects, high Pro-BNP and adiponectin, low myocardial restriction, and worse nutritional status were prevalent. In obesity, hypoadiponectinemia stimulates cardiac remodeling, cardiac hypertrophy, and decreased stretching, rendering Pro-BNP levels low despite high ultrafiltration rates. Thus, adiponectin correlates inversely with BMI, probably playing different cardiovascular roles as BMI changes.

Topics: Adiponectin; Aged; Aged, 80 and over; Body Mass Index; Cardiomegaly; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prospective Studies; Renal Dialysis

Obesity may reduce diagnostic accuracy of B-type natriuretic peptide (BNP) and affect long-term outcome.. This study evaluated patients included in the BASEL study (N = 452). We compared BNP levels in patients with (n = 86) and without (n = 366) obesity (body mass index <30 and >30 kg/m(2)) and determined sensitivities and specificities of BNP in both patient groups by receiver-operating characteristic analysis. Impact of BNP measurements on patient management and outcome in obesity, as well as 360-day mortality, was assessed.. The BNP levels were lower in obese patients (172 pg/mL [interquartile range 31-515] vs 306 [interquartile range 75-1,040]). The optimal BNP cut-point to detect heart failure was 182 pg/mL in obese patients and 298 pg/mL nonobese patients. Obese patients had lower in-hospital mortality (3.5% vs 8.5%, P = .045) and 360-day mortality (15% vs 30%, P = .001). In obese patients, the determination of BNP levels reduced time to initiation of the appropriate treatment (96 +/- 98 vs 176 +/- 230, P < .05) without impacting other end points.. Adjustment of BNP values in the assessment of obese patients presenting with acute dyspnea seems necessary to improve diagnostic accuracy and patient management. Obese patients had half the short- and long-term mortality of nonobese patients, independent of their final discharge diagnosis.

Topics: Aged; Aged, 80 and over; Biomarkers; Dyspnea; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prognosis; Prospective Studies; ROC Curve; Sensitivity and Specificity; Single-Blind Method

Hemodynamic mechanism for brain edema forrmation in patients with hypertensive encephalopathy is unclear. Potential roles of natriuretic peptides in the pathogenesis of hypertensive encephalopathy are discussed. A 32-year-old man presented with slight left hemiparesis. He was slightly confused, and his blood pressure was extremely high. Cranial plain computerized tomography scans revealed diffuse brain edema mainly in the supratentorial white matter region. Blood examination revealed that plasma concentrations of atrial and brain natriuretic peptides were significantly high. His left hemiparesis disappeared within a day, but he tended to be agitated. His altered mental status, however, resolved with control of blood pressure. Serial magnetic resonance imagings demonstrated that the magnitude of brain edema was attenuated in proportion to decline in plasma concentrations of natriuretic peptides. This case suggests that significant elevation of plasma concentrations of natriuretic peptides may contribute to an acute rise in blood pressure, and that these peptides potentially play an important role in development of brain edema in hypertensive encephalopathy.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Brain; Brain Injuries; Humans; Hypertensive Encephalopathy; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Obesity; Radiography; Renin-Angiotensin System; Time Factors

The mechanisms underlying the reduction in blood pressure that occurs with a severe energy-restricted diet were evaluated in 12 obese subjects during 8 days on a very-low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium per day. The relationship between changes in blood pressure, sodium balance, plasma volume, renin-aldosterone and sympathetic nervous system activities, plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF) prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1) concentrations was investigated. A negative sodium balance was present throughout the diet and was associated with a moderate reduction in plasma volume, a marked activation of the renin-aldosterone system, and a concomitant reduction in C- and N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal proANF and ANF secretion documented before the diet, disappeared after 8 days of dieting, in contrast to a greater postural stimulation of aldosterone and renin. A negative correlation was found between the changes of C- and N-terminal ANF prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP, and ET-1 remained unchanged. These results indicate that the decrease in blood pressure occurring during severe caloric restriction was essentially due to the reduction in the effective blood volume, as reflected by the stimulation of the renin-aldosterone system and the decrease in ANF levels. The lack of any changes in catecholamine excretion and endothelin levels suggests that peripheral vascular resistance did not change significantly in these circumstances.

Topics: Adolescent; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Body Weight; Catecholamines; Creatinine; Data Interpretation, Statistical; Diet, Reducing; Electrolytes; Endothelin-1; Female; Food Deprivation; Heart Rate; Hormones; Humans; Hydrocortisone; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Obesity; Plasma Volume; Renin; Sodium; Starvation; Uric Acid

N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy.. This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions.. Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged.. · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Topics: Biomarkers; Comorbidity; Female; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pregnancy

Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted.. We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (-2 standard deviation [SD] < SMI ≤-1 [SD]), and severely LMM groups (SD ≤-2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors.. This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89).. Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Topics: Adult; Cross-Sectional Studies; Humans; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Obesity; Republic of Korea

Topics: Acetates; Animals; Atrial Natriuretic Factor; Diet, High-Fat; Male; Natriuretic Peptide, Brain; Obesity; Rats; Rats, Wistar

Topics: Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; ROC Curve

The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.. In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.. Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49-2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59-2.69]; non-diabetes: HR 1.85 [1.68-2.02]), BMI (diabetes: HR 1.30 [1.18-1.42]; non-diabetes: HR 1.40 [1.35-1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55-2.75]; non-diabetes: HR 2.86 [2.50-3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82-2.80]; non-diabetes: HR 2.97 [2.21-4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19-1.34]; non-diabetes: HR 1.43 [1.39-1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04-1.16]; non-diabetes: HR 1.13 [1.10-1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03-1.24]; non-diabetes: HR 1.29 [1.25-1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9-52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3-16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7-17.4]), and hyperglycemia (glucose, 12.0% [4.2-19.9]).. The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.

Topics: Adult; Biomarkers; Blood Glucose; C-Reactive Protein; Diabetes Mellitus; Europe; Female; Health Status; Heart Disease Risk Factors; Heart Failure; Humans; Incidence; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prevalence; Prognosis; Risk Assessment; Time Factors; Troponin I

Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists.. We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool.. High-volume bariatric center.. Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography.. Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery.

Topics: Bariatric Surgery; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Preoperative Care; Stroke Volume; Ventricular Function, Left

Data regarding complex relationships between age, sex, obesity and N-terminal pro B-type natriuretic peptide (NT-proBNP) remain scarce. Thus, we investigated sex-specific associations of obesity and NT-proBNP levels among adults in the general healthy population in Korea.Methods and Results:The associations of age, sex and obesity-associated parameters (waist circumference [WC], body mass index [BMI] and body weight) with NT-proBNP were analyzed in 39,937 healthy adult participants. Multivariable regression models adjusted for factors known to affect NT-proBNP were used to identify associations between NT-proBNP and obesity-related parameters. NT-proBNP levels were higher in females than males. Older age was also associated with higher NT-proBNP levels in the overall population (P<0.001). When accounting for age in multivariable linear regression models, there was a strong inverse association between WC, BMI, and NT-proBNP in females and a weaker inverse association in males, with a significant difference between the sexes (P interaction <0.001). After adjusting for the effects of WC and BMI on each other, abdominal obesity was associated with lower NT-proBNP levels in females but not males (P interaction <0.001).. In this large sample of young and healthy Asians, younger age, male sex, and increases in obesity-related parameters were related to lower levels of NT-proBNP. Further comprehensive studies are needed to understand the factors affecting NT-proBNP levels in different populations.

Topics: Biomarkers; Body Mass Index; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Our objective was to examine the impact of caloric intake before or after the mean time of evening meal on cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.. Twelve patients with HFpEF and obesity completed a cardiorespiratory exercise test to measure CRF, defined as peak oxygen consumption (VO. Caloric intake after the mean time of evening meal was associated with better CRF in patients with HFpEF and concomitant obesity. Later nutrient intake may help prevent fasting related stress associated with cardiac metabolic disturbances present in HFpEF. Based on these findings, prospective trials aimed at examining the effects of later evening meal times in patients with HFpEF and obesity are warranted.

Topics: Aged; Biomarkers; Cardiorespiratory Fitness; Cross-Sectional Studies; Energy Intake; Exercise Tolerance; Feeding Behavior; Female; Heart Failure; Humans; Male; Meals; Middle Aged; Natriuretic Peptide, Brain; Obesity; Oxygen Consumption; Peptide Fragments; Prospective Studies; Stroke Volume; Time Factors; Ventricular Function, Left

The aim of this study was to study the prospective association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and changes in weight and obesity risk in a community-based population.. Data from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT-proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT-proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight.. The prevalence of obesity increased from 28% to 35% in the 6-year follow-up period. Compared with individuals in the highest NT-proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08-1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow-up (odds ratio 1.35; 95% CI: 1.07-1.69). Changes in NT-proBNP were inversely associated with weight change.. In this prospective study, lower levels of NT-proBNP were associated with higher risk of obesity, and changes in NT-proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity.

Topics: Biomarkers; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Risk Factors

Drug-induced long QT syndrome (DI-LQTS) is fatal and known to have a higher incidence in women rather than in men. Multiple risk factors potentiate the incidence of DI-LQTS, but the actual contribution of obesity remains largely unexplored. Correspondingly, the present study is aimed to evaluate the susceptibility of DI-LQTS in WNIN/Ob rat in comparison with its lean counterpart using 3-lead electrocardiography. Four- and eight-month-old female WNIN/Ob and their lean controls were used for the experimentation. Non-invasive blood pressure measurement and total body electric conductivity (TOBEC) analysis were carried out. After the baseline evaluations, animals were anesthetized with Ketamine (50 mg/kg). Haloperidol (12.5 mg/kg single dose) was administered intraperitoneally and ECG was taken at 0, 10, 20, 30, 60 min, and 24 h time points. Myocardial lystes were used to assess the BNP, protein carbonylation, and hydroxyproline content. Adiposity, as assessed by TOBEC, is higher in obese rats with elevated mean arterial blood pressure. Baseline-corrected QT interval (QTc) is significantly higher in the obese rat with a wider QRS complex. The incidence of PVC and VT are more intense in the obese rat. Haloperidol-induced QT prolongation in obese rats was rapidly induced than in lean, which was observed to remain till 24 h in obese groups while normalized in lean controls. Higher levels of BNP, protein carbonylation, hydroxyproline content, and relative heart weights indicated the presence of cardiac hypertrophy. The study provides preliminary evidence that obesity can be a potential risk factor for DI-LQTS with faster onset and longer subsistence.

Topics: Adiposity; Animals; Antipsychotic Agents; Cardiomegaly; Disease Models, Animal; Female; Haloperidol; Heart Rate; Hydroxyproline; Long QT Syndrome; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Protein Carbonylation; Rats, Inbred Strains; Risk Assessment; Risk Factors; Time Factors

Topics: Adult; Aged; Autopsy; Betacoronavirus; Biomarkers; Cardiovascular Diseases; Cell Death; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Endothelium; Female; Heart; Humans; Lymphopenia; Male; Microscopy, Electron; Middle Aged; Muscle Cells; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Obesity; Pandemics; Pneumonia, Viral; Renal Insufficiency, Chronic; SARS-CoV-2; Troponin I

Background Circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, a well-known indicator of atrial wall stress and remodeling, inversely correlate with body mass index. Both are strongly predictive of atrial fibrillation (AF). Their potential interaction in relation to incident AF, however, has not been explored. Methods and Results In total, 9556 participants of the ARIC (Atherosclerosis Risk in Communities) study who had 2 measurements of NT-proBNP and no baseline AF or heart failure were followed from 1996 to 1998 through 2016 for the occurrence of incident AF. Participants were categorized as obese (body mass index ≥30) and nonobese (body mass index <30) and by NT-proBNP levels (using the median of 68.2 pg/mL as the cutoff). Over a median follow-up of 18.3 years, we identified 1806 incident cases of AF. Analysis using multivariable Cox regression models showed that obese participants with high NT-proBNP levels at visit 4 had a higher adjusted risk of incident AF (hazard ratio: 3.64; 95% CI, 3.15-4.22) compared with nonobese individuals with low NT-proBNP levels. The association of obesity with AF risk was not modified by NT-proBNP levels (

Topics: Atrial Fibrillation; Biomarkers; Body Mass Index; Female; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; United States; Up-Regulation

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

Mid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls.. MR-proANP plasma levels were significantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were significantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concentrations correlated with inflammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and inflammation markers.. Our study emphasizes the role of circulating MR-proANP as a biomarker in critically ill patients, in which high MR-proANP indicates organ dysfunction, sepsis and mortality risk. The association between high MR-proANP and inflammatory as well as adipose tissue-derived endocrine mediators warrants further pathophysiological investigations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Comorbidity; Critical Illness; Diabetes Mellitus; Female; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; ROC Curve; Sepsis; Young Adult

Present study aims to explore the pathophysiological role of microRNA (miR)-29a in the process of obesity-related cardiomyopathy in human subjects and mice.. The expression level of circulating exosomal miR-29a was measured in 37 lean and 30 obese human subjects, and correlated with cardiac parameters. The effects of miR-29a on mitochondrial activity and cardiac function were investigated by treatment of miR-29a sponge in primary mouse cardiomyocytes and diet-induced obesity-related cardiomyopathy in mice.. The increased circulating miR-29a level was closely associated with impaired human cardiac function, including ejection fraction (r = -0.2663, p < 0.05) and NT-proBNP levels (r = 0.4270, p < 0.001). Exosomes from obese human plasma mediated cardiomyocyte mitochondrial inactivity, but pre-treatment with miR-29a sponge attenuated the exosomal miR-29a-induced reduction of ATP production (p < 0.001), basal oxygen consumption (p < 0.01) and mitochondrial complex I activity (p < 0.01). In vivo mouse study, high fat diet damaged cardiac function, normal structure, and mitochondrial activity, whereas miR-29a sponge improved the cardiac status.. Present study uncovered the correlation between circulating miR-29a and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-29a sponge in combating obesity-mediated cardiac dysfunction.

Topics: Animals; Cardiomyopathies; Diet, High-Fat; Exosomes; Humans; Male; Mice, Inbred C57BL; MicroRNAs; Middle Aged; Mitochondria, Heart; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Stroke Volume

Background Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high-risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin-3), FSTL3 (follistatin-like 3 peptide), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) to identify stage B MHD in young obese participants free of clinically evident cardiovascular disease. Methods and Results Asymptomatic obese patients (n=250) and non-obese controls (n=21) underwent echocardiographic cardiac phenotyping. Obese patients were classified as MHD positive ( MHD - POS ; n=94) if they had abnormal diastolic function or left ventricular hypertrophy and had estimated pulmonary artery systolic pressure ≥35 mm Hg. Obese patients without such abnormalities were classified as MHD negative (MHD-NEG; n=52). Serum biomarkers timed with echocardiography. MHD - POS and MHD-NEG individuals were similarly obese, but MHD - POS patients were older, with more diabetes mellitus and metabolic syndrome. Right ventricular coupling was worse in MHD - POS patients ( P<0.001). GAL 3 levels were higher in MHD - POS versus MHD -NEG patients (7.7±2.3 versus 6.3±1.9 ng/mL, respectively; P<0.001). Both GAL 3 and FSTL 3 levels correlated with diastolic dysfunction and increased pulmonary artery systolic pressure but not with left ventricular mass. In multivariate models including all 3 biomarkers, only GAL 3 remained associated with MHD (odds ratio: 1.30; 95% CI , 1.01-1.68; P=0.04). Conclusions In young obese individuals without known cardiovascular disease, GAL 3 is associated with the presence of preclinical MHD . GAL 3 may be useful in screening for preclinical MHD and identifying individuals with increased risk of progression to obesity-related heart failure with preserved ejection fraction.

Topics: Adult; Biomarkers; Blood Proteins; Case-Control Studies; Echocardiography; Female; Follistatin-Related Proteins; Galectin 3; Galectins; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Metabolic Diseases; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Black individuals have lower natriuretic peptide levels and greater risk of heart failure (HF) than white individuals. Higher N-terminal-pro-B-type natriuretic peptide (NT-proBNP) is associated with increased risk of incident HF, but little information is available in black individuals. We examined race-specific differences in 1) the association of NT-proBNP with incident HF and 2) the predictive ability of NT-proBNP for incident HF across body mass index (BMI) and estimated glomerular filtration rate (eGFR) categories.. In a prospective case-cohort study, baseline NT-proBNP was measured among 687 participants with incident HF and 2,923 (weighted 20,075) non-case randomly selected participants. Multivariable Cox proportional hazard modeling was used to assess the objectives of our study. Global Wald Chi-square score estimated from multivariable Cox models was used to assess predictive ability of NT-proBNP across BMI and eGFR categories.. In the multivariable model, a doubling of NT-proBNP concentration was associated with greater risk of incident HF among white individuals [hazard ratio (HR): 1.73; 95% CI: 1.55-1.94] than black individuals (HR: 1.51; 95% CI: 1.34-1.70); Pinteraction by race = 0.024. Higher NT-proBNP was the strongest predictor of incident HF across all BMI and eGFR categories among white individuals. By contrast, among black individuals with obesity (BMI ≥ 30 kg/m2) or eGFR < 60 mL/min/1.73 m2, the predictive ability of NT-proBNP for incident HF was attenuated.. The magnitude of the association of higher NT-proBNP with incident HF risk was greater among white individuals than black individuals. The diminished ability of NT-proBNP to predict the risk of HF in black population with obesity or impaired kidney function highlights the need of further investigations.

Topics: Aged; Body Mass Index; Female; Glomerular Filtration Rate; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Risk Assessment; Risk Factors

Topics: Glycosylation; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Peptide Fragments; Threonine

A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to control the maintenance of cardiovascular health through the regulation of cardioprotective epoxyeicosatrienoic acids (EETs) and its less active products, dihydroxyeicosatrienoic acids (DHETs). Therefore, we examined the role of the aforementioned pathway in the development of diabetic cardiomyopathy. Our diabetic model initiated cardiomyopathy as indexed by the increase in the expression of hypertrophic markers such as NPPA. Furthermore, diabetic cardiomyopathy was associated with a low level of cardiac EETs and an increase of the DHETs/EETs ratio both in vivo and in cardiac cells. The modulation in EETs and DHETs was attributed to the increase of sEH and the decrease of CYP2J. Interestingly, the reduction of sEH attenuates cardiotoxicity mediated by high glucose in cardiac cells. Mechanistically, the beneficial effect of sEH reduction might be due to the decrease of phosphorylated ERK1/2 and p38. Overall, the present work provides evidence that diabetes initiates cardiomyopathy through the increase in sEH, the reduction of CYP2J, and the decrease of cardioprotective EETs.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Line; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Eicosanoids; Epoxide Hydrolases; Extracellular Signal-Regulated MAP Kinases; Humans; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; Streptozocin

New-onset atrial fibrillation (NOAF) is a complication not infrequent in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) and has been associated with worse in-hospital and long-term prognosis. We aimed to develop and validate a risk score based on common clinical risk factors and routine blood biomarkers to assess the early incidence of NOAF post-pPCI, before discharge.. The risk score for NOAF occurrence during hospitalisation (about 5 days) was developed in a cohort of 1135 consecutive STEMI patients undergoing pPCI while was externally validated in a temporal cohort of 771 STEMI patients. Biomarkers and clinical variables significantly contributing to predicting NOAF were assessed by multivariate Cox-regression analysis.. The ALBO risk score, comprising biomarkers and clinical variables that can be assessed in hospital setting, could help to identify high-risk patients for NOAF after pPCI so that a prompter action can be taken.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Cohort Studies; Female; Humans; Incidence; Kaplan-Meier Estimate; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Percutaneous Coronary Intervention; Proportional Hazards Models; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction

Obese subjects have lower natriuretic peptide levels, but males and females have different anthropometric characteristics and fat distribution. Whether obesity-associated lowering of natriuretic peptides differs among males and females is unknown. Therefore, we investigated sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels among adults in the general population.. Using 8260 participants (50.1% females) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, we evaluated the relationship of NT-proBNP levels with obesity-associated parameters, i.e. waist circumference (WC), body mass index (BMI) and body weight in the overall population, and in males and females separately. NT-proBNP levels were higher in females (median, interquartile range: 50.5, 28.2-87.0 ng/L) than in males (24.3, 10.1-54.6 ng/L; P < 0.001). In the overall population, NT-proBNP levels were significantly lower in heavier individuals and displayed a 'U-shaped' relationship with increasing WC, but were not associated with BMI. After sex stratification, there was no significant association between NT-proBNP concentrations and anthropometric measures in females. However, in males increasing WC and BMI were associated with higher NT-proBNP levels (P < 0.05) while increasing body weight was associated with slightly lower NT-proBNP levels (P < 0.05). Age strongly confounded the association of NT-proBNP levels with obesity, and age-associated increases in NT-proBNP were significantly higher in males than in females (P < 0.001). In multivariable adjusted analyses, the inverse association of obesity and NT-proBNP levels was also significantly modified by sex: NT-proBNP levels were lower with increasing WC, BMI and body weight among females compared with males (P. Natriuretic peptide deficiency in obesity mostly pertains to females with abdominal obesity, whereas the relationship between obesity and natriuretic peptides appears to be more complex in males.

Topics: Adult; Body Mass Index; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Obesity; Peptide Fragments; Population Surveillance; Prognosis; Prospective Studies; Risk Factors; Sex Distribution; Sex Factors

Topics: Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Obesity

The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells.. Mice with a floxed GC-A gene were bred to Rip-Cre. In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation.. Our studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Proliferation; Disease Models, Animal; Disease Progression; Gene Deletion; Genetic Predisposition to Disease; Glucose Intolerance; Insulin; Insulin-Secreting Cells; Mice, Knockout; Natriuretic Peptide, Brain; Obesity; Phenotype; Receptors, Atrial Natriuretic Factor; Signal Transduction; Tissue Culture Techniques

Pregnancy is characterized by complex physiological changes of the cardiovascular system. B-type natriuretic peptides, represented by the bioactive molecule (BNP) and its inactive amino terminal fragment (NT-proBNP) are important biomarkers used in the management of the heart failure. Besides cardiac causes, BNP can grow in other noncardiac conditions such as pregnancy. The levels of natriuretic peptides during pregnancy have been the subject of multiple studies, whether it is a normal pregnancy, or there are pre-existing or developed cardiac conditions during pregnancy. It depends on the stage of pregnancy and comorbidities: obesity, preeclampsia, pre-existing cardiomyopathies or peripartum cardiomyopathy. High levels of NT-proBNP in pregnancy are associated with increased risk of cardiovascular events and involve careful supervision of pregnancy, including imaging procedures.

Topics: Biomarkers; Cardiomyopathies; Female; Heart; Heart Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pregnancy; Prognosis; Risk Factors

Topics: Body Mass Index; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Obesity; Registries

Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients.. The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent.. This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.

Topics: Aged; Female; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Obesity; Risk Factors

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

NTproBNP and BNP levels are reduced in obese subjects, but population-based data comparing the pattern of this relationship in the full spectrum of insulin-resistance mediated conditions, overweight/obesity, metabolic syndrome and diabetes, are limited.. The study-base were 3244 individuals aged 45-74 years, none of whom had heart failure, 1880 without diabetes and 1364 with diabetes, identified as part of two surveys of the population-based Casale Monferrato Study. All measurements were centralized. We examined with multiple linear regression and cubic regression splines the relationship between NTproBNP and BMI, independently of known risk factors and confounders. A logistic regression analysis was also performed to assess the effect of overweight/obesity (BMI ≥ 25 kg/m. NT-proBNP levels are lower in overweight/obesity, even in those with diabetes. Both insulin-resistance and chronic low-grade inflammation are involved in this relationship. Further intervention studies are required to clarify the potential role of drugs affecting the natriuretic peptides system on body weight and risk of diabetes.

Topics: Aged; Biomarkers; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Insulin Resistance; Italy; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Population Surveillance

BACKGROUND Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. MATERIAL AND METHODS Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. RESULTS A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. CONCLUSIONS The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model.

Topics: Animals; Blood Pressure; Body Weight; Cardiomegaly; Diet, High-Fat; Disease Models, Animal; Estradiol; Female; Gene Expression; Heart Ventricles; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Ovariectomy; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor

In whites, the minor G allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with higher circulating levels of ANP and B-type natriuretic peptide (BNP), lower risk of hypertension, higher high-density lipoprotein (HDL) cholesterol plasma levels, and lower prevalence of obesity and metabolic syndrome. The observed phenotype is consistent with the blood pressure lowering and metabolic properties of ANP and BNP. The cardiovascular and metabolic phenotype associated with rs5068 genotypes in African Americans is undefined. We genotyped 1631 African Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) for rs5068 and investigated their phenotype. Genotype frequencies of rs5068 were 93.2% AA (n = 1520), 6.7% AG (n = 110) and 0.1% GG (n = 1). All subsequent analyses are AG + GG versus AA genotype. Using a Bonferroni corrected level of significance of 0.005, the prevalence of metabolic syndrome (23% vs 38%, age-sex-adjusted p = 0.002) and triglycerides plasma values (76 vs 90 mg/dl, age-sex-BMI adjusted p = 0.004) were both significantly lower in the AG+GG genotypes. In the AG+GG genotypes, the prevalence of diabetes (8% vs 18%, age-sex-BMI-adjusted p = 0.02) and insulin plasma levels tended to be lower (4.8 vs 5.7 μU/ml, age-sex-BMI adjusted p = 0.04) whereas HDL-cholesterol levels tended to be higher (55 vs 50 mg/dl, age-sex-BMI-adjusted p = 0.04). No association was found with hypertension. The association between the rs5068 G allele and a favorable metabolic phenotype is now shown in African Americans. The rs5068 AG+GG genotypes are associated with lower prevalence of metabolic syndrome and lower triglycerides values.

Topics: Aged; Aged, 80 and over; Alleles; Atherosclerosis; Atrial Natriuretic Factor; Black or African American; Cardiovascular Diseases; Cardiovascular System; Cholesterol, HDL; Cohort Studies; Ethnicity; Female; Genotype; Geography; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity; Phenotype; Prevalence; Triglycerides; United States

Obesity is a risk factor for heart failure (HF) and identification of symptomatic, and obese HF patients are challenging, because obesity can mimic HF symptoms. We aimed to evaluate novel biomarkers for HF in obese subjects of the general population.. Midregional proadrenomedullin (MR-proADM), growth differentiation factor-15 (GDF-15), midregional pro-atrial natriuretic peptide (MR-proANP), and NT-proBNP were measured in 5000 individuals of the population-based Gutenberg Health Study (GHS), including 1204 obese individuals (BMI ≥ 30 kg/m. NT-proBNP and MR-proANP were lower in obese vs. non-obese HF individuals (p = 0.013 and p = 0.01, respectively), whereas GDF-15 was similar and MR-proADM was higher in obese vs. non-obese HF individuals. All biomarkers increased the odds ratio (OR) for prevalent HF. For NT-proBNP and MR-proANP, this increase was lower in obese vs. non-obese individuals, whereas it was comparable for MR-proADM and GDF-15. All biomarkers were associated with increased all-cause mortality (median follow-up 7.3 years, 211 events). Results were validated in 8373 individuals (n = 1734 with BMI ≥ 30 kg/m. All biomarkers were associated with HF and higher risk for all-cause mortality in the general population. In contrast to the natriuretic peptides NT-proBNP and MR-proANP, the novel biomarkers MR-proADM and GDF-15 were not lower in obese HF individuals, indicating their potential to facilitate HF diagnosis and prognosis in an increasingly obese HF population.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Growth Differentiation Factor 15; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Factors

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

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

Human studies suggest that insulin resistance and obesity are associated with a decrease in B-type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high-fat, high-fructose (HFHF) diet for 4 weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide 3-kinase-AKT (PI3K-AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF-fed mice compared with control animals. Exposure of cardiomyocytes to 100 nm insulin activated PI3K-AKT signalling (15 min) and induced a 1.9 ± 0.3-fold increase in BNP gene expression (6 h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100 nm) for 48 h induced insulin resistance, characterized by an impaired response of the PI3K-AKT signalling pathway and a decreased response of the BNP gene expression to insulin. The decreased response in BNP gene expression was reproduced by treating cardiomyocytes for 7 h with a PI3-kinase inhibitor (wortmannin). In conclusion, HFHF diet in vivo, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K-AKT pathway in vitro all decrease BNP mRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin-resistant individuals.

Topics: Androstadienes; Animals; Blood Glucose; Diet; Diet, High-Fat; Enzyme Inhibitors; Gene Expression; High Fructose Corn Syrup; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Triglycerides; Wortmannin

Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories.. We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese.. Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population.

Topics: Atherosclerosis; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Residence Characteristics; Risk Factors

The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress.. This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms.. Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits.. We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells.. Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling.

Topics: Adult; Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Gene Expression Regulation; Hep G2 Cells; Humans; Male; Mice; MicroRNAs; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Peptide Fragments; Protein Precursors; RNA, Messenger; Signal Transduction; Sodium

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

Whether body composition is associated with the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in acute coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of body composition on the NT-proBNP level and its prognostic performance among ACS patients.. In total, 1623 ACS patients with NT-proBNP data were enrolled. Percent body fat and lean mass index were estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator equation. Patients were divided into three groups according to the tertiles of sex-specific body mass index, percent body fat, or lean mass index. The endpoints were death from any cause and cardiovascular death.. Body mass index was inversely correlated with NT-proBNP levels (β = -0.036, P = 0.003). Lean mass index, but not percent body fat, was inversely associated with NT-proBNP levels (β of lean mass index = -0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes. Multivariate Cox analysis showed that the NT-proBNP level independently predicted all-cause mortality or cardiovascular death in the lower body mass index, lean mass index, and percent body fat groups. However, the prognostic performance of NT-proBNP was attenuated in patients with high body mass index, lean mass index, and percent body fat. In the subgroup of patients with diabetes, inverse associations between NT-proBNP levels and body mass index or body composition were not observed. In addition, the negative influence of high body mass index and body composition on the prognostic performance of the NT-proBNP level appeared to be attenuated.. Body mass index and lean mass index, but not percent body fat, are inversely associated with NT-proBNP levels. The prognostic performance of this biomarker may be compromised in patients with high body mass index, percent body fat, or lean mass index. Additionally, the influence of body composition on the NT-proBNP level and its prognostic performance might be attenuated in diabetic patients with ACS.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Body Composition; Cohort Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prognosis; Risk Factors

Plasma B-type natriuretic peptide (BNP) levels may vary widely among patients with similar stages of heart failure, in whom obesity might be the only factor reducing plasma BNP levels. We investigated the effect of obesity and body mass index (BMI) on plasma BNP levels using serial measurements before and after treatment (pre- and post-BNP and pre- and post-BMI) in patients with acute heart failure.. Multiple regression analysis and covariance structure analysis were performed to study the interactions between clinical factors in 372 patients. The pre-BMI was shown as a combination index of obesity and fluid accumulation, whereas the post-BMI was a conventional index of obesity.. There was a significant inverse correlation between BMI and BNP in each condition before and after treatment for heart failure. The direct significant associations of the log pre-BNP with the log post-BNP (β: 0.387), the post-BMI (β: -0.043), and the pre-BMI (β: 0.030) were analyzed by using structural equation modeling. The post-BMI was inversely correlated, but importantly, the pre-BMI was positively correlated, with the log pre-BNP, because the pre-BMI probably entailed an element of fluid accumulation. There were few patients with extremely high levels of pre-BNP among those with high post-BMI, due to suppressed secretion of BNP.. The low plasma BNP levels in true obesity patients with acute heart failure are of concern, because plasma BNP cannot increase in such patients.

Topics: Aged; Aged, 80 and over; Body Mass Index; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Regression Analysis

To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF).. 1119 patients admitted for AE-CHF and with NT-proBNP levels >900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality.. During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p<.001), and anemia (p<.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission.. Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions.

Topics: Aged; Aged, 80 and over; Anemia; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; End Stage Liver Disease; Female; Heart Failure; Heart Transplantation; Hospitalization; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Proportional Hazards Models; Retrospective Studies; Sex Factors

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

Topics: Adipokines; Adiponectin; Adipose Tissue; Leptin; Natriuretic Peptide, Brain; Obesity

Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium-phosphate homoeostasis. The data of recently published studies suggest that FGF-23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF-23 (C-terminal) and iFGF-23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population.. The analysis included 3115 elderly subjects (1485 women). During three visits, a questionnaire survey, comprehensive geriatric assessment and anthropometric measurements were performed as well as blood and urine samples were collected by trained nurses. Serum phosphorus, calcium, intact parathormone (iPTH), 25(OH)D3 , iFGF-23 and cFGF-23, insulin, glucose, albumin (also in urine), creatinine, hs-CRP, interleukin-6 and NT-proBNP concentrations were assessed. HOMA-IR was calculated according to the standard formula.. Both forms of FGF23, iPTH and 25-OH-D3 levels were not related to the occurrence of obesity and insulin resistance. Increase in phosphorus, iPTH and NT-proBNP concentrations is associated with rise in plasma iFGF23 and cFGF23 levels. Additionally, increase in hs-CRP explained the elevated plasma iFGF23 levels. In multiple regression models, circulating iFGF23 and cFGF23 level's variability in elderly population were explained by changes in serum phosphorus, iPTH, eGFR, hs-CRP and NT-proBNP levels but not by BMI and HOMA-IR values.. In conclusion, our study shows that increased levels of both circulating Fibroblast growth factor 23 forms in elderly subjects are associated with inflammation but not obesity or insulin resistance per se.

Topics: Aged; Calcifediol; Energy Metabolism; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Geriatric Assessment; Health Surveys; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Male; Natriuretic Peptide, Brain; Obesity; Parathyroid Hormone; Peptide Fragments; Poland; Regression Analysis

Obesity induces cardiovascular alterations, including cardiac hypertrophy, impaired relaxation, and heart rate variability (HRV), which are associated with increased mortality. Gastric bypass surgery (GBP) reduces cardiovascular mortality, but the mechanisms involved are not clearly established. To date, the implication of postsurgical hormonal changes has not been tested. Our aim was to study the relationships between the evolution of cardiovascular functions after GBP and changes in metabolic and hormonal parameters, including glucagon-like peptide-1 (GLP-1) and brain natriuretic peptide (N-terminal pro-brain natriuretic peptide (NT-proBNP)).. Echocardiographic parameters, 24-h rhythmic Holter recording, plasma concentrations of GLP-1 before and after a test meal, and fasting NT-proBNP were assessed in 34 patients (M/F 2/32, age 36 ± 11 years, BMI 46 ± 6 kg/m(2)), before and 1 year after GBP.. After GBP, excess weight loss was 79 ± 20%. Blood pressure (BP), heart rate, and left ventricular mass decreased, while HRV and diastolic function (E/A ratio) improved. Plasma concentrations of NT-proBNP and postprandial (PP) GLP-1 increased. Changes in cardiovascular parameters were related to BMI and insulin sensitivity. Furthermore, the decrease in BP was independently associated with the increase of PP GLP-1 level and HRV was positively associated with NT-proBNP concentration after surgery.. The increase in endogenous GLP-1 observed after GBP was associated with decreased BP but not with improvement of other cardiovascular parameters, whereas the increase in NT-proBNP, within the physiological range, was associated with improved HRV.

Topics: Adult; Blood Pressure; Female; Gastric Bypass; Glucagon-Like Peptide 1; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Weight Loss

Obesity in patients with heart failure (HF) is a factor of better prognosis, supposedly partly because of the particular epidemiology of HF in this population. This study expected to compare the parameters of severity and mortality in patients with and without obesity, to better understand the origin of this paradox.. Two hundred twenty-two patients with nonischemic HF and systolic dysfunction were divided into two groups according to their body mass index (≥ 30 vs. < 30 kg/m(2), respectively) and explored for functional parameters and prognosis.. B-type natriuretic peptide (BNP) levels were lower and peak oxygen consumption higher in patients with obesity. Patients with obesity had a better prognosis than patients without obesity with a 4-year mortality of 11.1% and 26.4%, respectively (P = 0.009). By univariate analysis, obesity was associated with a reduced risk of death: HR 0.52 [0.28-0.99]. This protective effect was no longer present after adjusting for VO2max and BNP level.. The obesity paradox is probably partly due to an overestimation of the severity of HF in patients with obesity because of the multifactorial nature of their dyspnea. Obesity no longer has a protective effect after adjustment for the usual prognostic parameters of HF.

Topics: Aged; Biomarkers; Body Fat Distribution; Body Mass Index; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prognosis; Severity of Illness Index

Chagas cardiomyopathy is a chronic sequela of infection by the parasite, Trypanosoma cruzi. Advanced cardiomyopathy is associated with a high mortality rate, and clinical characteristics have been used to predict mortality risk. Though multiple biomarkers have been associated with Chagas cardiomyopathy, it is unknown how these are related to survival.. This study aimed to identify biomarkers associated with mortality in individuals with severe Chagas cardiomyopathy in an urban Bolivian hospital.. The population included individuals with and without T. cruzi infection recruited in an urban hospital in Santa Cruz, Bolivia. Baseline characteristics, electrocardiogram findings, medications, and serum cardiac biomarker levels (B-type natriuretic peptide [BNP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatine kinase-myocardial band [CK-MB], troponin I, matrix metalloproteinase [MMP]-2, MMP-9, tissue inhibitor of metalloproteinases [TIMP] 1 and 2, transforming growth factor [TGF] beta 1 and 2) were ascertained. Echocardiograms were performed on those with cardiac symptoms or electrocardiogram abnormalities at baseline. Participants were contacted approximately 1 year after initial evaluation; deaths were reported by family members. Receiver-operating characteristic curves (ROC) were used to optimize cutoff values for each marker. For markers with area under the curve (AUC) >0.55, Cox proportional hazards models were performed to determine the hazards ratio (HR) and 95% confidence interval (CI) for the association of each marker with mortality.. The median follow-up time was 14.1 months (interquartile range 12.5, 16.7). Of 254 individuals with complete cardiac data, 220 (87%) had follow-up data. Of 50 patients with severe Chagas cardiomyopathy at baseline, 20 (40%) had died. Higher baseline levels of BNP (HR: 3.1, 95% CI: 1.2 to 8.4), NT-proBNP (HR: 4.4, 95% CI: 1.8 to 11.0), CK-MB (HR: 3.3, 95% CI: 1.3 to 8.0), and MMP-2 (HR: 4.2, 95% CI: 1.5 to 11.8) were significantly associated with subsequent mortality.. Severe Chagas cardiomyopathy is associated with high short-term mortality. BNP, NT-proBNP, CK-MB, and MMP-2 have added predictive value for mortality, even in the presence of decreased ejection fraction and other clinical signs of congestive heart failure.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Bolivia; Chagas Cardiomyopathy; Cohort Studies; Creatine Kinase, MB Form; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Peptide Fragments; Prognosis; Proportional Hazards Models; Protective Factors; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transforming Growth Factor beta1; Transforming Growth Factor beta2; Troponin I

We examined the hypothesis that insulin resistance (IR) decreases circulating concentrations of N-terminal (NT)-probrain natriuretic peptide (BNP). Obesity, despite being a risk factor for heart failure (HF), is paradoxically associated with lower concentrations of BNP, a marker of myocardial stress. Low BNP in obesity is postulated to be due to IR; however, it has been difficult to define the role of IR independent of obesity. IR in rheumatoid arthritis (RA) is increased, independent of obesity, thus allowing potential mechanistic insights into the relationship between IR and BNP. We measured demographic factors, traditional cardiovascular risk factors, body mass index (BMI), markers of inflammation (interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor α (TNFα)), NT-proBNP, and IR by the homeostatic model assessment (HOMA) in 140 patients with RA and 82 control subjects. Patients with heart failure and coronary artery disease were excluded. We used multiple linear regression models to examine the relationship between HOMA and NT-proBNP in RA and controls and in RA alone, the additional effect of inflammation. As previously reported, NT-proBNP concentrations were higher in RA (median 80.49 pg/mL, IQR (23.67-167.08 pg/mL)) than controls (17.84 pg/mL (3.28-36.28 pg/mL)) (P < 0.001), and the prevalence of IR, defined by HOMA > 2.114, was higher among RA than controls (53 % vs. 15%, P > 0.001). HOMA was positively correlated with NT-proBNP (rho = 0.226, P = 0.007) in RA, but not in controls (rho = -0.154, P = 0.168). In a multivariable model adjusted for age, race, and sex, we found that increasing HOMA was statistically associated with increasing NT-proBNP concentrations in RA (P = 0.001), but not controls (P = 0.543) (P for interaction = 0.036). In RA subjects, when IL-6 was further included in the model, IL-6 (P = 0.0014), but not HOMA (P = 0.43), remained significantly associated with NT-proBNP, suggesting that IL-6 may be mechanistically involved in the relationship between IR and NT-proBNP in RA. We conclude that in patients with RA, insulin resistance is associated with higher, rather than the expected lower, concentrations of NT-proBNP and that this may be related to increased IL-6.

Topics: Arthritis, Rheumatoid; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Tumor Necrosis Factor-alpha

Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations.. Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively.. Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels.. There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Body Composition; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Prospective Studies

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

The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.. Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).. There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).. The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

Topics: Aged; Aged, 80 and over; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes Complications; Diabetes Mellitus; Female; Humans; Inflammation; Kidney; Kidney Diseases; Lipids; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Risk Factors

Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status.. A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2).. Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49-4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85-3.49), 2.72 (1.42-5.22), and for obese: 3.29 (1.04-10.40), reference, 3.74 (1.52-9.21).. Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

Topics: Adult; Aged; Female; Germany; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Risk Factors

The study sought to evaluate the association of obesity with a novel biomarker of subclinical myocardial injury, cardiac troponin T measured with a new high-sensitivity assay (hs-cTnT), among adults without clinical cardiovascular disease (CVD).. Laboratory evidence suggests a relationship between obesity and myocardial injury that may play a role in the development of heart failure (HF), but there is limited clinical data regarding this association.. We evaluated 9,507 participants in the ARIC (Atherosclerosis Risk in Communities) study without baseline CVD (Visit 4, 1996 to 1999). We assessed the cross-sectional association of body mass index (BMI) with high (≥14 ng/l) and measurable (≥3 ng/l) hs-cTnT levels after multivariable regression. We further evaluated the independent and combined associations of BMI and hs-cTnT with incident HF.. Higher BMI was independently associated with a positive, linear increase in the likelihood of high hs-cTnT, with severe obesity (BMI >35 kg/m(2)) associated with an odds ratio of 2.20 (95% confidence interval: 1.59 to 3.06) for high hs-cTnT after adjustment. Over 12 years of follow-up, there were 869 incident HF events. Obesity and hs-cTnT were both independently associated with incident HF, and individuals with severe obesity and high hs-cTnT had a greater than 9-fold higher risk of incident HF (hazard ratio: 9.20 [95% confidence interval: 5.67 to 14.93]) than individuals with normal weight and undetectable hs-cTnT.. Among individuals without CVD, higher BMI has an independent, linear association with subclinical myocardial injury, as assessed by hs-cTnT levels. Obesity and hs-cTnT provide independent and complementary prognostic information regarding the risk of incident HF.

Topics: Biomarkers; Body Mass Index; Cholesterol, LDL; Coronary Artery Disease; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Risk Factors; Sex Factors; Troponin T; Waist Circumference

An obesity paradox, a "paradoxical" decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure. However, the impact of BMI in patients with idiopathic pulmonary arterial hypertension (IPAH) has not been studied. This study aims to find out whether BMI is a prognostic factor in IPAH.. We analysed 173 patients with IPAH. The patients were subclassified into categories of BMI defined as: under-weight (< 18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight and obese (25 to 34.9 kg/m2). The three BMI groups had similar profiles in terms of haemodynamic parameters assessed by right heart catheterization and level of NT-proBNP. The overweight and obese group had higher age, and lower WHO functional class, larger left ventricular end-diastolic dimensions (LVEDDs) than the other two groups.The Kaplan-Meier survival curves for the three BMI categories demonstrated that the overweight and obese group had a significantly higher survival rate than the normal weight and underweight groups (log-rank test, P = 0.027, P = 0.000, respectively). In a stepwise forward regression, lower BMI, higher WHO functional class, lower cardiac index, smaller LVEDDs and absence of targeted medication remained independent predictors of mortality.. Excess body mass is a protective factor for death in patients with IPAH.

Topics: Adult; Biomarkers; Body Mass Index; Cardiac Catheterization; Familial Primary Pulmonary Hypertension; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Risk Factors; Survival Rate

Topics: Aged; Brazil; Cardiovascular Diseases; Cohort Studies; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity; Overweight; Predictive Value of Tests; Prognosis; Residence Characteristics

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

Natriuretic peptides (NPs) play an important role in obesity and aim of this study was to evaluate, in cardiac tissue of obese Zucker rats (O, n = 29) their transcriptomic profile compared to controls (CO, n = 24) by Real-Time PCR study; CNP protein expression was evaluated by immunostaining and immunometric tests. Myocardial histology was performed, confirming no alteration of organ structure. While ANP and BNP are cardiac peptides, CNP is mainly an endothelial hormone; thus its expression, as well as that of NPR-B and NPR-C, was also evaluated in kidney and lung of an animal subgroup (n = 20). In heart, lower BNP mRNA levels in O vs CO (p = 0.02) as well as ANP and CNP (p = ns), were detected. NPR-B/NPR-A mRNA was similar in O and CO, while NPR-C was numerically lower (p = ns) in O than in CO. In kidney, CNP/NPR-B/NPR-C mRNA was similar in O and CO, while in lung CNP/NPR-C expression decreased and NPR-B increased (p = ns) in O vs CO. Subdividing into fasting and hyperglycemic rats, the pattern of mRNA expression for each gene analyzed remained unchanged. The trend observed in heart, kidney and lung for CNP protein concentrations and immunohistochemistry reflected the mRNA expression. TNF-α and IL-6 mRNA were measured in each tissue and no significant genotype effect was detected in any tissue. The main NP variations were observed at the cardiac level, suggesting a reduced release by cardiac cells. The understanding of mechanisms involved in the modulation of the NP system in obesity could be a useful starting point for future clinical study devoted to identifying new obesity treatment strategies.

Topics: Animals; Cytokines; Disease Models, Animal; Gene Expression Profiling; Gene Expression Regulation; Inflammation Mediators; Kidney; Lung; Male; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Rats; Rats, Zucker; Transcriptome

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p<0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.

Topics: Adolescent; Adult; Cardiovascular Diseases; Child; Female; Humans; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Radioimmunoassay; Reference Values

According to some studies, polycystic ovarian syndrome (PCOS) patients have an increased risk for diabetes mellitus and often show an adverse cardiovascular risk profile. NT-proBNP was shown to have a high predictive value regarding cardiovascular events, especially in those without overt cardiovascular disease. The aim of this study was to investigate the levels of NT-proBNP in 70 women with PCOS and/or obesity in relation to other classical cardiovascular risk factors. There was no statistical difference between NT-proBNP levels between obese, lean PCOS and obese PCOS patients; between patients with or without metabolic syndrome; or between patients with different cardiovascular risk, according to The Androgen Excess and PCOS Society consensus. NT-proBNP does not show significant correlation to age, weight, BMI, WHR, WSR, systolic or diastolic blood pressure and results from oral glucose tolerance test (OGTT), except for immunoreactive insulin (IRI) at 120 min. NT-proBNP correlates weakly with HDL, but not with other indices of lipid metabolism.

Topics: Adult; Body Mass Index; Female; Humans; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Polycystic Ovary Syndrome; Young Adult

Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status.. We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters.. We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters.. Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease.

Topics: Austria; Biomarkers; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Obesity; Peptide Fragments; Renal Dialysis; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity; Serum Albumin; Statistics as Topic; Survival Rate; Water-Electrolyte Imbalance

B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, P<0.001). Log BNP(CS-AO) had a significant negative correlation with BMI (r=-0.558, P<0.001), waist circumference (WC) (r=-0.574, P<0.001), log FFA(AO) (r=-0.643, P<0.001), log triglyceride (r=-0.431, P<0.001), and log HOMA-IR (r=-0.463, P<0.001) and a significant positive correlation with left ventricular mass index (LVMI) (r=0.403, P=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.

Topics: Adult; Aged; Cardiac Catheterization; Fatty Acids, Nonesterified; Female; Humans; Hypertrophy, Left Ventricular; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Ventricular Dysfunction, Left

Obesity is often associated with left ventricular (LV) diastolic dysfunction (DD). Elevated N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) is considered a biomarker of LV dysfunction. Weight loss induced by bariatric surgery may improve LV DD, but conflicting results regarding NT-proBNP levels have been reported. Our objective was to determine the impact of bariatric surgery-induced weight loss on NT-proBNP levels and LV DD.. Seventy (70) patients were evaluated before and 6 and 12 months following a biliopancreatic diversion with duodenal switch (BPD-DS), and 33 subjects were followed as controls at baseline and 6 and 12 months later. Blood was collected for NT-proBNP measurement, and LV diastolic function was assessed with echocardiography.. Among the 103 severely obese patients, 82% presented some degree of LV DD. Systolic function was preserved in all subjects. Along with significant weight loss, LV DD significantly improved (P < 0.001) in the BPD-DS group, whereas there was no change in the control group. NT-proBNP levels decreased over time in the control group (P = 0.016) and increased in subjects following BPD-DS (baseline vs 6-month vs 12-month follow-up: 51.8 ± 62.8 vs 132.0 ± 112.9 vs 143.3 ± 120.4 pg/mL; P < 0.001). The most significant associations with changes in NT-proBNP levels were improvements in the metabolic profile.. In severely obese patients, NT-proBNP levels decrease with sustained obesity for 1 year. Despite significant improvements in LV DD following bariatric surgery, NT-proBNP levels increase. These results suggest that monitoring NT-proBNP levels following bariatric surgery may be misleading regarding LV DD and symptoms of dyspnea.

Topics: Adult; Bariatric Surgery; Biomarkers; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Weight Loss

Stress and heart failure are associated with increased systemic levels of chromogranin A (CGA). Here we analyzed the effects of marathon running on systemic CGA levels and the association with cardiac burden and stress.. We recruited 47 lean and obese runners for a 10week training program aiming at running a marathon. Heart rates, individual fitness and marathon finishing times were monitored. CGA, proBNP and troponin T levels were analyzed by ELISA.. We found a significant increase of CGA (+51%; p<0.01) in lean runners after marathon. The obese group showed the highest troponin T (0.22ng/ml; p<0.01) and proBNP (176.6ng/ml; p<0.01) levels. There were no correlations between proBNP, troponin T and CGA. An inverse correlation (r=-0.45; p<0.01) was found between CGA and finishing times.. Marathon running is associated with increased CGA levels. However, this does not seem to reflect cardiac burden but rather marathon induced stress.

Topics: Adiposity; Biomarkers; Chromogranin A; Enzyme-Linked Immunosorbent Assay; Germany; Heart Rate; Humans; Natriuretic Peptide, Brain; Obesity; Physical Endurance; Physical Fitness; Running; Stress, Physiological; Time Factors; Troponin T; Up-Regulation

Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics.. A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes.. High BMI was associated with better clinical outcomes in Japanese CHF patients.

Topics: Aged; Blood Urea Nitrogen; Body Mass Index; Comorbidity; Female; Heart Failure; Hemoglobins; Humans; Inpatients; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Prognosis; Retrospective Studies; Sodium

Childhood obesity is associated with an increased risk of atherosclerosis, which can be mediated by an increase in angiogenesis and inflammation. The objective was to investigate the association between body mass index (BMI) and circulating biomarkers of angiogenesis, inflammation, and cardiac dysfunction in children and adolescents.. The Genetic Park Study is a highly inclusive survey conducted in three isolated villages of southern Italy. One hundred fifty-one children and adolescents (age range 5-17 y, 45% male) were included and categorized as obese (BMI z-score ≥ 1.64, n = 38) or non-obese (n = 113). Metabolic and cardiovascular biomarkers included glucose, triacylglycerol, total cholesterol, high-density lipoprotein, vascular endothelial growth factor (VEGF), placental growth factor, soluble feline sarcoma virus (fms)-like tyrosine kinase-1, highly sensitive C reactive protein (hs-CRP), highly sensitive troponin T (hs-TnT), and N-terminal prohormone brain natriuretic peptide (NT-proBNP).. Obese subjects had higher levels of triacylglycerol (P = 0.03) and hs-CRP (P = 0.02) after adjustment for age and gender. Circulating levels of VEGF were directly associated with BMI z-score (r = 0.22, P = 0.007) and hs-CRP (r = 0.33, P < 0.001). BMI z-score was not associated with biomarkers of cardiac dysfunction (hs-TnT and NT-proBNP).. Increasing BMI was associated with plasma levels hs-CRP and VEGF, which are involved in the initiation and progression of atherosclerosis. The lack of association between BMI and markers of cardiac damage (hs-TnT) or ventricular volume overload (NT-proBNP) suggest that atherosclerotic risk may still at a preclinical stage in this population of obese but otherwise healthy young individuals. Collectively, this suite of biomarkers could provide mechanistic insights into the physiopathologic progression of cardiovascular risk associated with childhood obesity.

Topics: Adolescent; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Child, Preschool; Cholesterol; Cross-Sectional Studies; Female; Humans; Inflammation; Interviews as Topic; Italy; Lipoproteins, HDL; Male; Natriuretic Peptide, Brain; Neovascularization, Pathologic; Obesity; Risk Factors; Triglycerides; Troponin T; Vascular Endothelial Growth Factor A

Adiponectin was reported recently to have roles in the pathophysiology of preeclampsia. Moreover, elevation of adiponectin and brain natriuretic peptide (BNP) has been observed in preeclampsia. We examined the possible links between adiponectin and BNP in the pathophysiology of preeclampsia. We performed a cross-sectional study in 56 preeclampsia patients and 56 controls matched for gestational age and body mass index. The BNP, leptin, and adiponectin levels were measured by ELISA, and their mRNA expressions were evaluated in omental adipose tissue by real-time PCR. The effects of BNP on adiponectin and leptin mRNA expression and secretion were investigated in primary cultures of adipocytes from obese and normal-weight women. The BNP, adiponectin, and leptin levels were significantly higher in preeclampsia patients compared with controls. The adiponectin level was increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients. Adiponectin mRNA expression was increased significantly in adipose tissues of preeclampsia patients compared with controls and was also increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients, whereas leptin was not. BNP and adiponectin showed significant positive correlations in both normal-weight and overweight preeclampsia patients. BNP had a significantly weaker effect on adiponectin in overweight compared with normal-weight preeclampsia patients. Moreover, BNP had a weaker effect on adiponectin production in adipocytes from overweight women compared with adipocytes from normal-weight women using primary culture of human adipocytes. These data suggested that BNP may play a role in hyperadiponectinemia of preeclampsia patients. The weaker effect of BNP on adiponectin production may participate in the pathophysiology of overweight preeclampsia patients.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Adult; Body Mass Index; Cells, Cultured; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Natriuretic Peptide, Brain; Obesity; Pre-Eclampsia; Pregnancy; Real-Time Polymerase Chain Reaction

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

To investigate whether objective cardiovascular parameters have an independent association with nocturnal voiding in women.. Thirty-two parameters derived from questionnaires, and anthropometric, physiological and biochemical measures of 5,980 women were applied for analysis. Nocturnal voiding was assessed by the International Prostate Symptom Score and the Overactive Bladder Symptom Score. We measured variables including previously reported correlates of nocturnal voiding, such as age, a history of hypertension, and a history of diabetes, as well as those focusing on cardiovascular function, such as the cardio-ankle vascular index, the augmentation index, the ankle-brachial index, plasma B-type natriuretic peptide (BNP), and C-reactive protein (CRP).. Age [odds ratio (OR): 1.058, P < 0.001], length of sleep (OR: 1.194, P < 0.001), sleeplessness (OR: 2.841, P < 0.001), urgency (OR: 1.528, P < 0.001), log(BNP) (OR: 2.031, P < 0.001), waist circumference (OR: 1.037, P = 0.002), body mass index (OR: 0.935, P = 0.007), menopause (OR: 1.503, P = 0.043), and history of hypertension (OR: 1.225, P = 0.029) were independently associated with nocturnal voiding ≥2 times. Age (β = 0.256, P < 0.001), urgency (β = 0.195, P < 0.001), sleeplessness (β = 0.181, P < 0.001), length of sleep (β = 0.088, P < 0.001), log(BNP) (β = 0.072, P < 0.001), waist circumference (β = 0.086, P < 0.001), and low-density lipoprotein-cholesterol (β = -0.038, P = 0.003) were significantly correlated with the severity of nocturnal voiding.. Plasma BNP, which represents cardiac load, is strongly associated with the prevalence and severity of nocturnal voiding in Japanese women, as well as previously known correlates including age, urgency, quality and quantity of sleep, and obesity.

Topics: Adult; Aged; Ankle Brachial Index; Asian People; Biomarkers; C-Reactive Protein; Comorbidity; Female; Humans; Japan; Logistic Models; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Nocturia; Obesity; Odds Ratio; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Sex Factors; Sleep; Surveys and Questionnaires

To compare volume overload in stable hemodialysis (HD) patients assessed by standard clinical judgment with data obtained from bioimpedance analysis.. Ultrafiltration volume (VU) was delivered as prescribed by standard clinical practice. Independently, a measure for volume overload was assessed by a clinical score (SW). The Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany) was used to derive values for extracellular volume (VE) and volume overload (VO) before HD. Arterial pressures (P0, P1) and serum levels of NT-pro-BNP (B0, B1) were evaluated before and after HD.. In 28 patients (11 women, age: 51.3 ± 13.3 y, body mass index (BMI) 18.5 - 40.9 kg/m2; VE: 17.91 ± 3.45 l) delivered VU was 2.41 ± 1.03 l and not different from VO of 2.08 ± 1.49 l derived from bioimpedance analysis. There was no correlation between VO and VU (r = -0.15, p = 0.46) but a negative correlation between the difference VO - VU (i.e., the volume overload at treatment end) and BMI (r = -0.49, p < 0.01). Positive correlations were observed between B0 and the relative volume overload (= VO/VE) (r = 0.58, p < 0.001).. The well recognized relationship between cardiac natriuretic peptides and volume expansion was confirmed. The volume overload at treatment end (VO - VU) was negligible for the whole group of patients but more negative with increasing BMI. It therefore appears that in comparison to bioimpedance-based evaluation the clinical judgment overestimates volume overload in obese patients which leads to the delivery of high ultrafiltration volumes and to volume contraction at the end of a dialysis session in this group of patients.

Topics: Adult; Austria; Biomarkers; Blood Pressure; Blood Volume; Body Composition; Body Mass Index; Chi-Square Distribution; Electric Impedance; Extracellular Fluid; Female; Humans; Kidney Diseases; Male; Middle Aged; Models, Biological; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Renal Dialysis; Treatment Outcome

Brain natriuretic peptide (BNP) levels are lower in obese patients with left ventricular failure than in their comparably ill, leaner counterparts. The effect of obesity on BNP in patients with pulmonary arterial hypertension (PAH) is unknown. We reviewed our prospective PAH registry data collected from November 2001 to December 2007 for patients undergoing right heart catheterization who met the criteria for PAH and had the BNP level and body mass index determined at baseline. The median BNP level for the lean, overweight, and obese patients was 285 pg/ml (interquartile range 131 to 548), 315 pg/ml (interquartile range 88 to 531), and 117 pg/ml (interquartile range 58 to 270), respectively (p = 0.029). A greater body mass index was associated with a lower BNP level, adjusted for age, gender, New York Heart Association functional class, hypertension, coronary artery disease, and mean right atrial and pulmonary arterial pressures (p <0.001). No statistically significant differences were found among the groups in age, race, medical co-morbidities, underlying etiology of PAH, use of vasoactive medications, New York Heart Association functional class, echocardiographic parameters, or pulmonary function. Obese patients had greater right atrial and pulmonary artery pressures. Increased BNP was associated with worse survival in the lean and overweight patients only. In conclusion, the BNP levels are attenuated in obese patients with PAH despite similar or worse hemodynamics or functional class compared to lean or overweight patients and should therefore be interpreted with caution.

Topics: Body Mass Index; Cardiac Catheterization; Echocardiography; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Prospective Studies; Survival Analysis; Thinness

Prominent features of myocardial remodeling in heart failure with preserved ejection fraction (HFPEF) are high cardiomyocyte resting tension (F(passive)) and cardiomyocyte hypertrophy. In experimental models, both reacted favorably to raised protein kinase G (PKG) activity. The present study assessed myocardial PKG activity, its downstream effects on cardiomyocyte F(passive) and cardiomyocyte diameter, and its upstream control by cyclic guanosine monophosphate (cGMP), nitrosative/oxidative stress, and brain natriuretic peptide (BNP). To discern altered control of myocardial remodeling by PKG, HFPEF was compared with aortic stenosis and HF with reduced EF (HFREF).. Patients with HFPEF (n=36), AS (n=67), and HFREF (n=43) were free of coronary artery disease. More HFPEF patients were obese (P<0.05) or had diabetes mellitus (P<0.05). Left ventricular myocardial biopsies were procured transvascularly in HFPEF and HFREF and perioperatively in aortic stenosis. F(passive) was measured in cardiomyocytes before and after PKG administration. Myocardial homogenates were used for assessment of PKG activity, cGMP concentration, proBNP-108 expression, and nitrotyrosine expression, a measure of nitrosative/oxidative stress. Additional quantitative immunohistochemical analysis was performed for PKG activity and nitrotyrosine expression. Lower PKG activity in HFPEF than in aortic stenosis (P<0.01) or HFREF (P<0.001) was associated with higher cardiomyocyte F(passive) (P<0.001) and related to lower cGMP concentration (P<0.001) and higher nitrosative/oxidative stress (P<0.05). Higher F(passive) in HFPEF was corrected by in vitro PKG administration.. Low myocardial PKG activity in HFPEF was associated with raised cardiomyocyte F(passive) and was related to increased myocardial nitrosative/oxidative stress. The latter was probably induced by the high prevalence in HFPEF of metabolic comorbidities. Correction of myocardial PKG activity could be a target for specific HFPEF treatment.

Topics: Aortic Valve Stenosis; Biopsy; Cohort Studies; Comorbidity; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Diabetes Mellitus; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Obesity; Oxidative Stress; Stroke Volume; Tyrosine

Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.

Topics: Adaptation, Physiological; Adult; Atrial Natriuretic Factor; Cells, Cultured; Gene Expression Regulation; Genes, Mitochondrial; Heat-Shock Proteins; Humans; Lipid Metabolism; Male; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Natriuretic Peptide, Brain; Obesity; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Primary Cell Culture; Receptors, Atrial Natriuretic Factor; Signal Transduction; Transcription Factors; Up-Regulation

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

Obesity has numerous adverse effects on general, and especially, cardiovascular health. Plasma adiponectin, an adipokine, is inversely related to adipose tissue mass, and also the prognosis of heart failure and coronary artery disease (CAD). Coronary artery bypass grafting (CABG) surgery is usually the treatment of choice for patients with complex CAD.. To investigate the impact of body mass index (BMI) and the associated biomarkers on clinical outcomes after CABG.. Patients with CAD who underwent CABG by a single cardiac surgeon team were prospectively enrolled and followed for up to 5 years after CABG.. Among the 234 consecutive patients (aged 70.4 ± 10.5 years, BMI 24.68 ± 3.27 kg/m(2), 84.6% men), there were 76 mortalities during follow-up. BMI was negatively correlated with adiponectin (r=-0.203, p=0.003), high-sensitivity C-reactive protein (hsCRP; r=-0.176, p=0.009), and N-terminal pro-brain natriuretic peptide (NT-proBNP; r=-0.271, p<0.001). Patients of normal weight (BMI <25 kg/m(2)) had a decreased event free survival when compared with overweight or obese patients (BMI ≥25 kg/m(2)). After accounting for age, sex, manifest acute coronary syndrome, glomerular filtration rate, and left ventricular ejection fraction, BMI remained correlated with cardiovascular mortality in the study population. (HR and 95% CI per 1 kg/m(2): 0.912 (0.833 to 0.998)). However, adiponectin, hsCRP, and NT-proBNP would abolish the prognostic impact of BMI. In addition, risk-stratified subgroup analysis showed that adiponectin, hsCRP and NT-proBNP predicted mortality in patients with normal weight, rather than in overweight or obese patients.. BMI was inversely associated with the prognosis of CABG. Such association may be linked to the baseline mechanisms related to metabolic disorder (adiponectin) and systemic inflammation (hsCRP). Future pathophysiological validation is indicated.

Topics: Adiponectin; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; C-Reactive Protein; Coronary Artery Bypass; Coronary Artery Disease; Epidemiologic Methods; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity; Prognosis

To examine the influence of obesity on the predictive value of the pro-B-type natriuretic peptide (NT-proBNP) assay in acute myocardial infarction.. Prospective observational study.. All intensive care units in one region of France. Patients 2217 consecutive patients admitted for an acute myocardial infarction matched with respect to age, gender, Killip class and renal function.. Cardiovascular death at one year.. There were three groups (according to body mass index (BMI): obese, overweight and normal) of 739 matched patients. Median levels of NT-proBNP were considerably lower in high BMI patients, by about 20% in overweight and by 60% in obese patients, compared with normal BMI patients. An inverse relationship between the propeptide values and BMI was found in the overall study population (r = -0.20, p < 0.0001), and for both genders. In multivariate linear regression, BMI as a continuous variable was a predictor of the log NT-proBNP level, even when adjusted for potential confounders. CV mortality at 1-year follow-up was similar for the three BMI groups (p = 0.691). In multivariate logistic regression analysis, log NT-proBNP predicted mortality in normal (OR (95% CI) 3.48 (2.00 to 6.12)) and overweight (OR (95% CI) 3.96 (1.95 to 8.06)) patients, even when adjusted for confounders (GRACE risk score, left ventricular ejection fraction). However, in obese patients, propeptide levels failed to retain their independent prognostic value (OR (95% CI) 1.34 (0.86 to 2.08)).. In this large population of patients with myocardial infarction, circulating NT-proBNP levels were considerably lower in obese patients; the significance of the propeptide level as an independent prognostic factor is severely compromised.

Topics: Aged; Biomarkers; Body Mass Index; Female; France; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Prospective Studies; Survival Analysis

Increased plasma amino-terminal-cleavage-fragment of NP (NT-proBNP) is an established indicator for heart failure. Moreover, obese adults had low circulating NT-proBNP suggesting an obesity-related dysregulation (natriuretic handicap). Secretion and/or clearance of NT-proBNP were discussed to be impaired in obesity. As only older adults were investigated so far, it remains unclear when during the evolution of obesity the state of a natriuretic handicap develops, and whether NT-proBNP may still serve as a relevant cardiac marker in obese juveniles.. We analysed NT-proBNP in juvenile (n=274, 10-18 years) and middle-aged (n=277, 18-50 years) normal weight (n=213) and obese (n=338) probands together with complex anthropometry, carotis sonography, clinical, and laboratory parameters.. NT-proBNP showed a significant gender and age interaction. Adult females had significant higher NT-proBNP than adult males, and higher levels than juvenile females. Adult males had lower levels than juvenile males. Only a weak age and weight interaction was seen with obese juveniles which showed higher NT-proBNP than obese adults. Moreover, normal weight probands had higher NT-proBNP than overweight and obese. In a multiple regression including all probands, gender, creatinine and uric acid were the best predictors for NT-proBNP. In adults, female gender is the strongest driver for increased NT-proBNP.. These results argue against an essential influence of obesity to B-type cardiac natriuretic hormone system regulation in the absence of heart failure, and suggest NT-proBNP as a useful cardiac marker irrespective of age and obesity.

Topics: Adolescent; Adult; Body Weight; Child; Disease Progression; Family; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Regression Analysis; Young Adult

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

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

Menopause is associated with weight gain and an increase of cardiovascular risk. The aim of the present study was to estimate serum ischemia-modified albumin (IMA) levels in postmenopausal women and evaluate their association with body mass index (BMI) and coronary artery disease (CAD).. The study included 130 non-smoker postmenopausal women aged 43-80: 40 with BMI 26-32 kg/m(2) (Group A), 60 with BMI 21-25 kg/m(2) (Group B), and 30 with documented CAD and BMI 23-29 kg/m(2) (Group C). Serum IMA, albumin, hsCRP and NT-proBNP, glucose and insulin were measured. Homeostasis assessment model score (HOMA) and Quantitative insulin sensitivity index (QUICKI) were co-estimated.. Serum IMA and IMA to albumin ratio were significantly elevated in Group A as compared to Group B (p<0.001) and similar to those of Group C. hsCRP and NT-proBNP did not differ between Groups A and B while they were lower in comparison to Group C (p<0.001). Glucose, insulin and HOMA were elevated in Group A compared to Group B (p<0.001) while QUICKI was lower (p<0.001). In Group A, IMA was positively correlated with BMI, hsCRP, insulin, HOMA and negatively with QUICKI. In postmenopausal women, multivariable regression analysis revealed that obesity was the strongest significant determinant of circulating IMA levels (p<0.001) contributing, therefore, to the elevated serum IMA concentration.. Postmenopausal obesity is associated with elevated serum IMA possibly due to obesity associated oxidative stress. IMA measurement could provide an assessment of atherosclerotic burden in postmenopausal women. Further clinical evaluation is under investigation.

Topics: Adult; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Coronary Artery Disease; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Oxidative Stress; Peptide Fragments; Postmenopause; Serum Albumin; Serum Albumin, Human

The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown.. The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction.. We studied 7770 individuals from the Framingham Heart Study (n = 3833, 54% women) and the Malmö Diet and Cancer study (n = 3918, 60% women). We examined the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP) with obesity, insulin resistance, and various metabolic subtypes.. Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham, P = 0.001 in Malmö), whereas insulin resistance was associated with 10-30% lower levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were insulin sensitive had only modest reductions in N-BNP compared with nonobese, insulin-sensitive individuals. On the other hand, individuals who were nonobese but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower N-BNP in Malmö (P < 0.001), compared with nonobese and insulin-sensitive individuals. Adjustment for serum-free testosterone did not alter these associations.. In both nonobese and obese individuals, insulin resistance is associated with lower natriuretic peptide levels. The relative natriuretic peptide deficiency seen in obesity could be partly attributable to insulin resistance, and could be one mechanism by which insulin resistance promotes hypertension.

Topics: Adult; Androgens; Body Mass Index; Cohort Studies; Diet; Female; Humans; Hyperinsulinism; Insulin Resistance; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Predictive Value of Tests; Testosterone

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

To investigate the effect of body mass index (BMI) on heart rate variability (HRV) and inflammatory parameters in patients with heart failure.. We analyzed 55 consecutive patients (mean age, 63.5 +/- 12.8 years; male/female, 39/16) with symptomatic left ventricular systolic (ejection fraction <45%) heart failure. The participants were classified into three categories according to BMI: lean (BMI < 25 kg/m2), overweight (BMI = 25-29.9 kg/m2) and obese (BMI >or= 30 kg/m2). The cause of heart failure was mainly ischemic heart disease (75%) with mean ejection fraction 30 +/- 7%. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein levels were measured, and time-domain HRV indices were determined on Holter electrocardiogram. The relationship between HRV indices and laboratory, inflammatory and echocardiographic parameters was investigated with correlation analysis.. Age, sex, clinical characteristics (hypertension, diabetes mellitus, dyslipidemia, family history, smoking) were similar between groups. BMI was inversely correlated with NT-pro BNP levels (P = 0.001). HRV indices did not differ between groups. Correlation analysis demonstrated the relationship between HRV indices and fasting blood glucose (SDNN, SDANN, SDNNI, root mean square successive differences, VTI), C-reactive protein (SDANN, SDNNI, VTI), pulmonary artery pressure (SDNN, SDANN, VTI) levels.. In systolic heart failure patients a higher BMI is associated with decreased NT-proBNP levels. Although HRV indices were not different between groups, inflammatory parameters, fasting blood glucose and pulmonary artery pressure were correlated with them.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Heart Failure; Heart Rate; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

The relationships between N-terminal fragment proBNP (B-type natriuretic peptide) (NT-proBNP) and sex steroid hormones have not been fully elucidated. We examined these associations in pre-, peri- and postmenopausal women without known cardiovascular disease. We also examined the change in circulating NT-proBNP caused by a gonadotrophin-releasing hormone (GnRH) agonist in order to clarify the effect of acute hormone deficiency on NT-proBNP.. Forty-nine premenopausal women, 101 perimenopausal women and 108 postmenopausal women were enrolled in one study. Forty-four premenopausal women with leiomyoma were recruited for another study, and 22 of those women were treated with a GnRH agonist. Serum levels of NT-proBNP, estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured.. NT-proBNP concentrations showed significant inverse correlations with body mass index (BMI) in peri- and postmenopausal women. Serum NTproBNP concentrations showed significant positive correlations with SHBG in peri- and postmenopausal women. These significant correlations remained after adjustment for age and BMI. Serum NT-proBNP concentration was significantly decreased after GnRH agonist administration, while NT-proBNP concentration in the control group did not change significantly. Serum SHBG level was also significantly decreased after GnRH agonist administration.. Circulating NT-proBNP levels are positively associated with SHBG levels in non-obese peri- and postmenopausal women, and this relationship was found under the condition of acute hormone deficiency induced by GnRH agonist treatment.

Topics: Adult; Aging; Body Mass Index; Female; Gonadotropin-Releasing Hormone; Humans; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Perimenopause; Postmenopause; Premenopause; Sex Hormone-Binding Globulin

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

This study aimed to analyze the variations of N-terminal pro B-type natriuretic peptide, epicardial adipose tissue thickness, and carotid intima-media thickness in childhood obesity. The study participants consisted of 50 obese children in the study group and 20 nonobese children referred for evaluation of murmurs who proved to have an innocent murmur and were used as control subjects. All the subjects underwent transthoracic echocardiographic examination for determination of left ventricular systolic function and mass index, myocardial tissue rates, and myocardial performance index. Epicardial adipose tissue thickness and carotid intima-media thickness also were measured during echocardiography. Serum N-terminal pro B-type natriuretic peptide levels were measured at the time of evaluation. The left ventricle mass index was 40.21 + or - 10.42 g/m(2) in the obese group and 34.44 + or - 4.51 g/m(2) in the control group (p > 0.05). The serum N-terminal pro B-type natriuretic peptide level was 109.25 + or - 48.53 pg/ml in the study group and 51.96 + or - 22.36 pg/ml and in the control group (p = 0.001). The epicardial adipose tissue thickness was 5.57 + or - 1.45 mm in the study group and 2.98 + or - 0.41 mm in the control group (p = 0.001), and the respective carotid intima-media thicknesses were 0.079 + or - 0.019 cm and 0.049 + or - 0.012 cm (p = 0.001). The left ventricular systolic and diastolic functions showed no statistically significant correlations with N-terminal pro B-type natriuretic peptide levels, carotid intima-media thickness, or epicardial adipose tissue thickness values. The results show that measurement of serum N-terminal pro B-type natriuretic peptide level, carotid intima-media thickness, and epicardial adipose tissue thickness in asymptomatic obese children is not needed.

Topics: Adipose Tissue; Body Mass Index; Cardiovascular Diseases; Carotid Artery, Common; Child; Child, Preschool; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pericardium; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Tunica Intima; Ventricular Function, Left

Sibutramine is a selective inhibitor of the reuptake of monoamines. Plasma levels of brain natriuretic peptide (BNP) appear to be inversely associated with body mass index (BMI) in subjects with and without heart failure for reasons that remain unexplained. The aim of this study was to investigate the possible influence of sibutramine treatment on BNP levels in severely obese patients.. Fifty-two severely obese female patients with BMI > 40 kg/m(2) were included to this study. The women were recommended to follow a weight-reducing daily diet of 25 kcal/kg of ideal body weight. During the treatment period, all patients were to receive 15 mg of sibutramine once a day. Blood chemistry tests were performed before the onset of the medication and after 12 weeks of treatment.. None of the subjects was withdrawn from the study because of the adverse effects of sibutramine. Body weight (108.8 +/- 13.3 kg vs. 101.7 +/- 15.6 kg, p < 0.001), BMI (44.6 +/- 4.6 kg/m(2) vs. 41.8 +/- 5.7 kg/m(2), p < 0.001) and BNP [8.6 (0.5-49.5) ng/l vs. 3.1 (0.2-28.6) ng/l, p = 0.018] levels were significantly decreased after 12 weeks of sibutramine treatment. Total cholesterol (5.19 +/- 0.90 mmol/l vs. 4.82 +/- 1.05 mmol/l respectively; p < 0.001), low-density lipoprotein-cholesterol (3.26 +/- 0.86 mmol/l vs. 2.99 +/- 0.40 mmol/l respectively; p = 0.008), levels were significantly decreased; however, there was no significant alteration in high-density lipoprotein-cholesterol and triglyceride levels.. This study has shown a decrease in BNP levels which may lead to improvement in cardiac outcome after sibutramine treatment. Further randomised studies are needed to be conducted to clarify the relationship between sibutramine and BNP.

Topics: Appetite Depressants; Biomarkers; Body Mass Index; Cholesterol, LDL; Cyclobutanes; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity

The inverse association between plasma B-type natriuretic peptide (BNP) levels and body mass index (BMI) has been reported in Western populations. Here we analyzed the relationship between plasma BNP and obesity in a general urban Japanese population. We recruited 1,759 subjects without atrial fibrillation or history of ischemic heart disease aged 38-95 years (mean age +/- standard deviation 64.5 +/- 10.9 years, 56.1% women, mean BMI 22.8 +/- 3.1 kg/m(2)) from the participants in the Suita Study between August 2002 and December 2003. In multivariable regression analyses adjusted for age, systolic blood pressure, pulse rate, serum creatinine, left ventricular hypertrophy in ECG, the inverse relationships between BNP levels and BMI (kg/m(2)) was found in both sexes (both p<0.001). Multivariable-adjusted mean plasma BNP levels in the group of BMI<18.5, 18.5< or =BMI< 22, 22< or =BMI<25, and 25< or =BMI were 23.4, 17.9, 14.0 and 13.0 pg/mL, respectively (trend p<0.001). The negative association of body fat (percentage and mass), skin fold thickness, or waist circumference with BNP levels was observed the negative associations in both sexes (p<0.01). Among the obesity indices, body fat mass is most tightly associated with BNP. In conclusion, plasma BNP was inversely associated with obesity related markers such as body fat mass, skinfold thickness and waist circumferences after adjusted for relevant covariates in a Japanese population.

Topics: Adiposity; Adult; Aged; Body Composition; Body Mass Index; Female; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Regression Analysis; Skinfold Thickness; Urban Population; Waist Circumference

To explore the covariate-adjusted associations between body composition (percent body fat and lean body mass) and prognostic factors for mortality in patients with chronic heart failure (CHF) (nutritional status, N-terminal pro-B-type natriuretic peptide [NT-proBNP], quality of life, exercise capacity, and C-reactive protein).. Between June 2008 and July 2009, we directly measured body composition using dual energy x-ray absorptiometry in 140 patients with systolic and/or diastolic heart failure. We compared body composition and CHF prognostic factors across body fat reference ranges and body mass index (BMI) categories. Multiple linear regression models were created to examine the independent associations between body composition and CHF prognostic factors; we contrasted these with models that used BMI.. Use of BMI misclassified body fat status in 51 patients (41%). Body mass index was correlated with both lean body mass (r=0.72) and percent body fat (r=0.67). Lean body mass significantly increased with increasing BMI but not with percent body fat. Body mass index was significantly associated with lower NT-proBNP and lower exercise capacity. In contrast, higher percent body fat was associated with a higher serum prealbumin level, lower exercise capacity, and increased C-reactive protein level; lean body mass was inversely associated with NT-proBNP and positively associated with hand-grip strength.. When BMI is divided into fat and lean mass components, a higher lean body mass and/or lower fat mass is independently associated with factors that are prognostically advantageous in CHF. Body mass index may not be a good indicator of adiposity and may in fact be a better surrogate for lean body mass in this population.

Topics: Absorptiometry, Photon; Adult; Alberta; Analysis of Variance; Bias; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Chronic Disease; Cross-Sectional Studies; Exercise Tolerance; Female; Hand Strength; Heart Failure; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Obesity; Peptide Fragments; Prealbumin; Predictive Value of Tests; Prognosis; Quality of Life; Risk Factors

Plasma B-type natriuretic peptide (BNP) and proBNP are established markers of cardiac dysfunction. Even though obesity increases the risk of cardiovascular disease, obese individuals have reduced plasma concentrations of natriuretic peptides. The underlying mechanism is not established. We used cultured cardiomyocytes and three different mouse models to examine the impact of obesity and cardiac lipid accumulation on cardiac natriuretic peptide expression. The cardiac ventricular expression of atrial natriuretic peptide (ANP) and BNP mRNA and ANP peptide was decreased 36-72% in obese ob/ob, db/db, and fat-fed C57BL/6 mice as compared with their respective controls. The db/db and ob/ob mice displayed impaired cardiac function, whereas the fat-fed mice had almost normal cardiac function. Moreover, the ventricular expression of hypertrophic genes (α- and β-myosin heavy chain and α-actin) and natriuretic peptide receptor genes were not consistently altered by obesity across the three mouse models. In contrast, cardiac ventricular triglycerides were similarly increased by 60-115% in all three obese mouse models and incubation with oleic acid caused triglyceride accumulation and an approximately 35% (P < 0.005) depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function.

Topics: Animals; Atrial Natriuretic Factor; Cells, Cultured; Heart Ventricles; Mice; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Random Allocation; RNA, Messenger; Statistics, Nonparametric; Triglycerides

Natriuretic peptides have multiple beneficial cardiovascular effects. Previous cross-sectional studies have indicated that obese subjects have lower natriuretic peptide concentrations than those of normal weight. It is not known whether this relative natriuretic peptide deficiency is reversible with weight loss. We studied 132 obese subjects undergoing weight loss surgery with serial measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations at preoperative, early (1 to 2 months), and late postoperative (6 months) points. In addition, 20 subjects also underwent echocardiography at baseline and 6 months after surgery. Significant weight loss was observed after surgery (median body mass index 45.1, 41.0, and 32.9 kg/m(2) for the 3 corresponding points, analysis of variance p <0.001). The median NT-proBNP levels increased substantially (31.6, 66.9, and 84.9 pg/ml; p <0.001). The average intrasubject increase in NT-proBNP at the 2 postoperative points was 3.4 and 5.0 times the preoperative level (p <0.001 for both points vs preoperatively). In the multivariate regression models adjusted for clinical characteristics and insulin resistance, the strongest predictor of the change in NT-proBNP level 6 months after weight loss surgery was the change in weight (p = 0.03). Echocardiography showed a mean intrasubject reduction in left ventricular mass index of 18% (p <0.001) and mild improvements in diastolic function, with no change in ejection fraction. In conclusion, we have demonstrated that weight loss is associated with early and sustained increases in NT-proBNP concentrations, despite evidence of preserved systolic and improved diastolic function. These findings suggest a direct, reversible relation between obesity and reduced natriuretic peptide levels.

Topics: Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Weight Loss

We tested the association of the adipokines resistin and adiponectin with incident heart failure.. Abnormal concentrations of adipokines may partially explain the association between obesity and heart failure.. We related circulating adipokine concentrations to the incidence of heart failure in 2,739 participants in the Framingham Offspring Study.. During 6 years of follow-up, 58 participants developed new-onset heart failure. In proportional hazards models (adjusting for age, sex, blood pressure, antihypertensive treatment, diabetes, smoking, total/high-density lipoprotein cholesterol ratio, prevalent coronary heart disease, valvular heart disease, left ventricular hypertrophy, and estimated glomerular filtration rate) using the lowest third of the resistin distribution as the referent, the hazard ratios for heart failure in the middle and top thirds were 2.89 (95% confidence interval [CI]: 1.05 to 7.92) and 4.01 (95% CI: 1.52 to 10.57), respectively (p = 0.004 for trend). Additional adjustment for body mass index, insulin resistance (measured with the homeostasis model), C-reactive protein, and B-type natriuretic peptide did not substantively weaken this association (multivariable hazard ratios [HRs]: 2.62 and 3.74, p = 0.007). In the maximally adjusted model, each SD increment in resistin (7.45 ng/ml) was associated with a 26% increase in heart failure risk (95% CI: 1% to 60%). Concentrations of adiponectin were not associated with heart failure (multivariable HRs: 0.87 and 0.97, p = 0.9).. Increased circulating concentrations of resistin were associated with incident heart failure, even after accounting for prevalent coronary heart disease, obesity, and measures of insulin resistance and inflammation. The findings suggest a role for resistin in human disease and a novel pathway to heart failure.

Topics: Adiponectin; Adult Children; Biomarkers; C-Reactive Protein; Confidence Intervals; Exercise Tolerance; Female; Heart Failure; Humans; Inflammation; Insulin Resistance; Male; Massachusetts; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prospective Studies; Resistin; Risk Factors; United States

Plasma brain natriuretic peptide (BNP) level is known to reflect left ventricular wall stress (LVWS). Recent studies have shown that obese individuals have lower BNP levels. However, the usefulness of BNP level as a marker of LVWS in obese individuals remains unclear. This study examined whether BNP reflects LVWS even in obese individuals.This study enrolled 136 hospital inpatients who had suffered chronic heart failure (NYHA class I or II), or who had undergone a thorough examination for angina pectoris. On the basis of body mass index (BMI), we divided the inpatients into nonobese (< 25) and obese (> or = 25) groups. All BNP measurements, cardiac catheterizations, and echocardiographic examinations were carried out within 24 hours. Although no significant differences were found between the two groups in the hemodynamic parameters examined, including end-diastolic LVWS (LV-EDWS) and end-systolic LVWS (LV-ESWS), BNP levels were significantly lower in the obese group compared to the nonobese group. In the nonobese group, a definite correlation between LV-EDWS or LV-ESWS and BNP (r = 0.43, r = 0.46, respectively) was observed, whereas no correlation was found between LV-EDWS or LV-ESWS and BNP in the obese group (r = -0.09, r = 0.06, respectively). To explore the mechanism for suppressed BNP levels in obese individuals, the correlation of BNP with biochemical markers was analyzed. Statistical significance was found only between adiponectin and BNP (r = 0.44), implying that BNP or adiponectin might influence the plasma levels of the other.In conclusion, BNP levels cannot be used as a marker of LVWS in obese individuals.

Topics: Adiponectin; Aged; Algorithms; Biomarkers; Body Mass Index; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Retrospective Studies; Ventricular Function, Left

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

N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) is an established biomarker for heart failure in adults, while its plasma concentrations are altered in adult obesity. Plasma adiponectin concentrations are decreased in obesity and low levels are associated with disorders with an increased cardiometabolic risk. A few studies support an association between these two markers in adults with coronary heart disease. Such relations have not been investigated in children with obesity, which is the most prevalent risk factor for cardiovascular disease. Ninety-six children, 24 obese/25 normal BMI boys, and 23 obese/24 normal BMI girls, aged 10-16, were studied. Plasma NT-proBNP was measured using electrochemiluminescence, and adiponectin and other metabolic risk factors, such as glucose, insulin, cholesterol, triglycerides (TG), HDL, and LDL using standard methodology. The findings were gender dimorphic. In overweight and obese females (mean BMI z-score: 2.65+/-1.69), plasma NT-proBNP concentrations correlated significantly with adiponectin levels (r=0.4, r(2)=0.05, p=0.013), while in those with obesity defined as BMI z-score >2.5 (mean BMI z-score: 3.67+/-1.08, n=20) this association was stronger (r=0.6, r(2)=0.22, p=0.005). Adiponectin also correlated significantly with BMI z-scores, TG, HDL, and insulin levels. In boys, there was no correlation between NT-proBNP and adiponectin. NT-proBNP correlated significantly with HDL, while adiponectin correlated with TG, fasting insulin, and the Homeostasis Assessment Model (HOMA) Index. The positive association between NT-proBNP and adiponectin depends on the severity of obesity and is gender dimorphic. This positive correlation in females might be a potential protective mechanism against atherosclerosis in later life.

Topics: Adiponectin; Adolescent; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Cholesterol; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Risk Factors; Sex Characteristics; Triglycerides

Natriuretic peptides (NPs) have been characterized as vascular hormones that regulate vascular tone via guanylyl cyclase (GC), cyclic GMP (cGMP), and cGMP-dependent protein kinase (cGK). Recent clinical studies have shown that plasma NP levels were lower in subjects with the metabolic syndrome. The present study was conducted to elucidate the roles for NP/cGK cascades in energy metabolism.. We used three types of genetically engineered mice: brain NP (BNP) transgenic (BNP-Tg), cGK-Tg, and guanylyl cyclase-A (GCA) heterozygous knockout (GCA(+/-)) mice and analyzed the metabolic consequences of chronic activation of NP/cGK cascades in vivo. We also examined the effect of NPs in cultured myocytes.. BNP-Tg mice fed on high-fat diet were protected against diet-induced obesity and insulin resistance, and cGK-Tg mice had reduced body weight even on standard diet; surprisingly, giant mitochondria were densely packed in the skeletal muscle. Both mice showed an increase in muscle mitochondrial content and fat oxidation through upregulation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha and PPARdelta. The functional NP receptors, GCA and guanylyl cyclase-B, were downregulated by feeding a high-fat diet, while GCA(+/-) mice showed increases in body weight and glucose intolerance when fed a high-fat diet. NPs directly increased the expression of PGC-1alpha and PPARdelta and mitochondrial content in cultured myocytes.. The findings together suggest that NP/cGK cascades can promote muscle mitochondrial biogenesis and fat oxidation, as to prevent obesity and glucose intolerance. The vascular hormone, NP, would contribute to coordinated regulation of oxygen supply and consumption.

Topics: Animals; Blood Glucose; Cells, Cultured; Cyclic GMP; Dietary Fats; Down-Regulation; Genetic Engineering; Glucose Intolerance; Insulin Resistance; Lipid Peroxidation; Mice; Mice, Knockout; Mitochondria; Molecular Sequence Data; Muscle Cells; Muscle, Skeletal; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR delta; PPAR gamma; Protein Kinases; Receptors, Atrial Natriuretic Factor; Trans-Activators; Transcription Factors; Up-Regulation

To verify whether controlling for indicators of disease severity and confounders represents a solution to the obesity paradox in chronic heart failure (CHF).. From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m(2) (Group 3), BMI 20-24.9 k/m(2) (Group 1) and BMI 25-29.9 kg/m(2) (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78-1.05, chi(2): 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13-1.97, chi(2): 7.82) after multivariable adjustment.. The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.

Topics: Aged; Body Mass Index; Case-Control Studies; Confounding Factors, Epidemiologic; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Regression Analysis

Plasma brain natriuretic peptide (BNP) is a useful adjunct to diagnose and monitor patient with heart failure, but there are comorbidities such as chronic kidney disease or chronic pulmonary disease, which influence the interpretation of BNP levels.. We present a case of a young and very obese patient (body mass index [BMI] 72.6 kg/m(2)), who was presented with acute global heart decompensation. Echocardiography revealed a dilated left ventricle with an ejection fraction of 20% by global distributed heart with enlarged right heart caves. Computed tomography and X-ray demonstrated an extreme cardiomegaly with cardio-thoracic ratio of 0.71. Remarkably, laboratory measurements revealed only a slight elevated concentrations of brain natriuretic peptide (BNP) (443.2 pg/ml) and his inactive component NT-proBNP (1710 pg/ml). Despite maximized heart care clinical condition of the patient aggravated continuously so that the patient died after 6 days because of heart insufficiency.. Obese patients (body mass index [BMI] >30 kg/m(2)) with any given severity of heart failure obviously express lower levels of BNP. Until now, the cause for this phenomenon is unclear. Therefore caution should be exercised in interpreting BNP levels in such patients.

Topics: Biomarkers; Echocardiography; Fatal Outcome; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Young Adult

To investigate the relationship between body mass index (BMI) and N-terminal pro-brain natriuretic peptide (NTproBNP) level and resultant prognostic capacity in chronic heart failure (CHF) controlled for known confounders.. We formed 206 triplets of patients (n = 618) with stable systolic CHF matched with respect to age, sex, renal function (MDRD, modification of diet in renal disease formula), and NYHA class, each with a BMI >30 kg/m(2) (group 3), 20-24.9 kg/m(2) (group 1), and 25-29.9 kg/m(2) (group 2). BMI conveys a 4% drop in NTproBNP per unit increase. This influence remained significant after correction for age, sex, MDRD, NYHA, heart rate, rhythm, and ejection fraction. NTproBNP remained an independent predictor of adverse outcome after correction for age, sex, BMI, NYHA, MDRD, and ejection fraction. Despite numerical differences, prognostic power was comparable between BMI groups (log-transformed NTproBNP; group 1: hazard ratio (HR) 1.435, 95% CI 1.046-1.967, chi(2) 5.02, P = 0.03; group 2: HR 1.604, 95% CI 1.203-2.138, chi(2) 10.36, P = 0.001; group 3: HR 1.735, 95% CI 1.302-2.313, chi(2) 14.12, P = 0.0002) (P = NS, all). An NTproBNP correction factor was calculated.. Even matched for NYHA, age, sex, and renal function, BMI exerts a significant and independent inverse influence on NTproBNP in patients with stable CHF. NTproBNP retained equal statistical power in all three BMI groups.

Topics: Biomarkers; Body Mass Index; Chronic Disease; Epidemiologic Methods; Female; Germany; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Registries

We identify determinants of plasma interleukin-6 (IL-6) levels in a multicenter panel study of myocardial infarction (MI) survivors, using repeated measurements to evaluate both baseline and time-varying factors.. Survivors of MI (N= 1003) recruited in six European cities had repeated measurements (median: 6/patient) of IL-6. At baseline, participants' behaviour and medical histories were determined by interview, and blood pressure, anthropometry, cholesterol and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. Short-term exposures and medication intake were recorded at each visit. Generalized additive mixed models were used to analyze associations of IL-6 with baseline and time-varying risk factors, taking into account repeated measurements.. Age, hour of blood withdrawal, body mass index, pack-years of smoking, NT-proBNP, systolic blood pressure, high-density lipoprotein cholesterol, persistent cough/phlegm and statin use were significantly and independently associated with IL-6 after adjustment for city, recurrent MI, baseline alcohol intake, current active smoking, tea consumption and extreme anger or stress.. Among MI survivors, IL-6 levels are associated with many traditional cardiovascular risk factors. Patients with elevated NT-proBNP, respiratory symptoms or obesity had higher IL-6 concentrations and may potentially be at greater risk for coronary artery disease progression.

Topics: Adult; Age Factors; Aged; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Cough; Disease Progression; Europe; Female; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors; Time Factors; Up-Regulation; Ventricular Function, Left

Recent studies have shown that obesity is an independent predictor of lower N-terminal pro-BNP (NT-proBNP) levels and raised concerns about the validity of this biomarker in obese subjects. We evaluated the influence of obesity (body mass index>or=30 kg/m(2)) on the correlation between exercise capacity and serum NT-proBNP levels in 100 chronic heart failure (CHF) patients referred for cardiopulmonary exercise testing. Circulating NT-proBNP levels correlated well with lean body mass-adjusted peak oxygen consumption (VO(2)) in the entire cohort (R=-0.72, p<0.001) and in the obese (R=-0.71, p<0.001) and non-obese (R=-0.72, p<0.001) subgroups. There was no significant difference between the correlation coefficients of the two subgroups (p=0.934). In conclusion NT-proBNP levels predict exercise capacity in CHF patients irrespective of the presence of obesity.

Topics: Aged; Chronic Disease; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR.. We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR_ECC) and BMI.. The prognostic factors GFR_ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR_ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69.. The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR_ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR_ECC and BMI as an additional prognostic factor.

Topics: Age Factors; Aged; Blood Pressure; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Disease Progression; Female; Glomerular Filtration Rate; Humans; Insulin; Insulin Resistance; Male; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Obesity; Prognosis; Proteinuria; Renal Insufficiency

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

Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described.. One thousand one hundred three patients presenting to the emergency department with acute dyspnea underwent analysis. Patients were classified into the following 3 BMI categories: lean (<25.0), overweight (25.0-29.9), and obese (>/=30.0).. The NT-proBNP concentrations in the overweight and obese groups were significantly lower than in the lean patients, regardless of the presence of acute heart failure (P<.001). The positive likelihood ratio for an NT-proBNP-based diagnosis of acute heart failure was 5.3 for a BMI lower than 25.0, 13.3 for a BMI of 25.0 to 29.9, and 7.5 for a BMI of 30.0 or higher. A cut point of 300 ng/L had very low negative likelihood ratios in all 3 BMI categories (0.02, 0.03, and 0.08, respectively). Among decedents, the NT-proBNP concentrations were lower in the overweight and obese patients compared with the lean subjects (P<.001). Nonetheless, a single cut point of 986 ng/L strongly predicted 1-year mortality across the 3 BMI strata, regardless of the presence of acute heart failure (hazard ratios, 2.22, 3.06, and 3.69 for BMIs of <25.0, 25.0-29.9, and >/=30.0, respectively; all P<.004); the risk associated with a high NT-proBNP concentration was detected early and was sustained to a year after baseline in all 3 BMI strata (all P<.001).. In patients with and without acute heart failure, the NT-proBNP concentrations are relatively lower in overweight and obese patients with acute dyspnea. Despite this, the NT-proBNP concentration retains its diagnostic and prognostic capacity across all BMI categories.

Topics: Acute Disease; Aged; Biomarkers; Body Mass Index; Diagnosis, Differential; Dyspnea; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Precursors; Risk Factors

Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors.. We examined the association of plasma levels of B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3333 Framingham study participants free of heart failure (mean age, 58 years; 54% women). Regression analyses were performed, with adjustment for clinical and echocardiographic variables. Plasma natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were lower in persons with the metabolic syndrome compared with those without the metabolic syndrome: In men, B-type natriuretic peptide was 24% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 16% lower (P<0.001); in women, B-type natriuretic peptide was 29% lower (P<0.001) and N-terminal pro-atrial natriuretic peptide was 18% lower (P<0.001). Individuals with insulin resistance, as indicated by an elevated homeostasis model assessment (HOMA-IR) index, had lower levels of B-type natriuretic peptide (P=0.009 in men, P<0.001 in women) and N-terminal pro-atrial natriuretic peptide (P<0.001 in men, P=0.001 in women).. Having several metabolic risk factors is associated with low circulating natriuretic peptide levels, even after adjustment for body mass index. These findings raise the possibility that reduced natriuretic peptide activity is a manifestation of the metabolic syndrome, which may have important clinical and pathophysiological implications.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Body Mass Index; Female; Heart Failure; Humans; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Obesity; Protein Precursors; Risk Factors; Ultrasonography

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

Noninvasive left ventricular (LV) pressure estimation in obese patients has not been well described. Simultaneous B-type natriuretic peptide (BNP) and echocardiographic Doppler examinations were performed in patients with dyspnea undergoing cardiac catheterization. Patients were divided into body mass index (BMI) >35 (markedly obese), 31 to 35 (obese), and < or =30 kg/m2 (nonobese). BNP levels and mitral early diastolic/tissue Doppler annular velocity (E/Ea) were compared with invasively measured LV end-diastolic and pre-atrial (pre-A) pressures. Seventy-two patients were studied. Except for BMI, LV mass index, and LV diastolic dimension, there were no significant differences in baseline, echocardiographic Doppler, or hemodynamic characteristics among the groups. However, BNP was significantly lower in markedly obese compared with obese and nonobese patients (116 +/- 187 vs 241 +/- 674 and 277 +/- 352 pg/ml, respectively; p = 0.03). BNP did not correlate with LV pre-A pressure in markedly obese patients (R = 0.13, p = 0.47), whereas BNP significantly correlated with this variable in the obese (R = 0.64) and nonobese (R = 0.58) groups. Mitral E/Ea significantly correlated with LV pre-A and LV end-diastolic pressures in all BMI groups. In markedly obese patients with dyspnea, BNP did not correlate with invasively measured LV filling pressure, whereas this correlated in obese and nonobese patients. However, mitral E/Ea significantly correlated with LV filling pressures in all BMI groups. In conclusion, BNP is not recommended for LV filling pressure estimation in ambulatory patients with dyspnea with BMI >35 kg/m2.

Topics: Adult; Aged; Body Mass Index; Cardiac Catheterization; Dyspnea; Echocardiography, Doppler; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Prospective Studies; Ventricular Pressure

Suppressed plasma B-type natriuretic peptide (BNP) levels have been reported in obese individuals with heart failure (HF). However, the precise mechanism and significance of this relationship in the clinical setting of HF are unknown. Recently, we reported a close association between BNP levels and left ventricular end-diastolic wall stress (EDWS) as the underlying mechanism of BNP secretion; therefore, we investigated the relationship between BMI and plasma BNP levels in HF while adjusting for EDWS.. In 245 consecutive patients who presented with HF, we measured plasma BNP levels and performed echocardiography and cardiac catheterization. Meridional EDWS was calculated from echocardiographic and hemodynamic parameters. The body mass index (BMI) for the total population was 22.9 +/- 0.2 kg/m2; 21% were lean (BMI < 20) and 27% overweight and obese (BMI > or = 25). The correlation between plasma BNP and EDWS [r = 0.771 (P <.001)] was more robust than any other echocardiographic or hemodynamic parameter as well as any patient's characteristics. By a univariate analysis, BMI was inversely correlated with both BNP levels and EDWS (P <.001 in both). However, a multivariable regression analysis that took into account EDWS demonstrated a significant inverse association between BMI and BNP (P <.001).. The present study demonstrates that BMI determines the BNP level in a manner that is independent of the hemodynamic load in patients with HF. Overweight and obesity should be considered to be associated with the interindividual variability of plasma BNP levels in the diagnosis and management of HF patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Ventricular Dysfunction, Left; Ventricular Function, 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

Although recent studies show that obesity, or elevated body mass index (BMI), is associated with lower levels of B-type natriuretic peptide (BNP), it is unknown whether BMI affects the prognostic value of BNP in heart failure (HF). This study confirms the relationship between high BMI and low BNP in patients with advanced systolic HF. Despite relatively lower levels of BNP in overweight and obesity, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality in HF at all levels of BMI.. This study aimed to examine the influence of obesity on the predictive value of the B-type natriuretic peptide (BNP) assay in heart failure (HF).. Recent studies show that obesity, or elevated body mass index (BMI), is associated with lower circulating levels of BNP both in the general population and in patients with HF.. We analyzed data from 316 systolic HF (left ventricular ejection fraction [LVEF] < or =40%) patients [age, 53 +/- 13 years; mean LVEF, 24 +/- 7%; 48% ischemic] followed up at a university HF center. Patients were divided into categories of BMI: lean (BMI <25 kg/m2), overweight (BMI = 25 to 29.9 kg/m2), and obese (BMI > or =30 kg/m2).. The BNP levels were significantly lower in overweight and obese compared with lean patients (p = 0.0001); median BNP (interquartile range) for the lean (n = 131), overweight (n = 99), and obese (n = 86) groups was 747 (272 to 1,300), 380 (143 to 856), and 332 (118 to 617) pg/ml, respectively. In each BMI category, elevated BNP was significantly associated with worse symptoms and higher pulmonary capillary wedge pressure. Higher BNP was also a significant independent predictor of survival independent of BMI. Optimal BNP cutoff for prediction of death or urgent transplant in lean, overweight, and obese HF patients was 590, 471, and 342 pg/ml, respectively.. Although BNP levels are relatively lower in overweight and obese HF patients, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality at all levels of BMI.

Topics: Biomarkers; Body Mass Index; Female; Heart Failure; Heart Transplantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Prognosis; Stroke Volume

Topics: Adult; Body Mass Index; Female; Humans; Male; Natriuretic Peptide, Brain; Obesity

Further investigations are warranted to better characterize variables that may confound the clinical interpretation of plasma natriuretic peptide measurements, which are increasingly recognized to have diagnostic and predictive importance.. Blood samples (EDTA plasma) from patients (n = 206) attending clinics for the medical treatment and follow-up of obesity were analyzed for B-type natriuretic peptide (BNP; Bayer assay) and the N-terminal segment of its prohormone (NT-proBNP; Roche assay). Natriuretic peptide concentration ranges were evaluated in those without diagnosis of congestive heart failure (CHF) or chronic kidney disease (CKD).. BNP and NT-proBNP were directly correlated (r = 0.87; P = 0.01), with NT-proBNP concentrations higher relative to BNP. Of obese patients without CHF or CKD, 21.6% (40 of 185) had NT-proBNP concentrations greater than the published assay upper reference limit. Concentrations of both natriuretic peptides were higher in patients currently exposed to beta blockers, patients with the diagnosis of hypertension or type 2 diabetes, and patients with a history of gastric bypass surgery. An inverse relationship between body mass index (BMI) and both BNP and NT-proBNP was evident. According to the National Institutes of Health, National Heart, Lung, and Blood Institute classification, more than 95% of the participants sampled in this study were either obesity class 2 (35 kg/m(2) < BMI < 39.9 kg/m(2)) or class 3 (BMI >or=40 kg/m(2)). A substantial proportion of obese patients without CHF or CKD have concentrations greater than the upper reference limit for NT-proBNP but not for simultaneously measured BNP. A history of gastric bypass surgery appeared to be a significant predictor of increased natriuretic peptide concentrations when assessed in a population of patients with class 2 or 3 obesity.

Topics: Adult; Body Mass Index; Chronic Disease; Cross-Sectional Studies; Female; Gastric Bypass; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prospective Studies; Reference Values

B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis.. The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results.. Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients.. Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.

Topics: Acute Disease; Aged; Body Mass Index; Cohort Studies; Dyspnea; Female; Heart Failure; Humans; Male; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Obesity; Sensitivity and Specificity; Severity of Illness Index; Single-Blind Method

Topics: Aged; Atrial Fibrillation; Coronary Artery Bypass; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinase 1; Natriuretic Peptide, Brain; Obesity; Postoperative Complications; Risk; Tissue Inhibitor of Metalloproteinase-1

Topics: Adipose Tissue; Adult; Echocardiography, Doppler, Color; Female; Heart Diseases; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Viscera

The plasma concentrations of natriuretic peptides, BNP and NTproBNP, have been shown to be markers for the diagnosis of congestive heart failure (CHF). In this study, plasma BNP and NTproBNP concentrations were evaluated and stratified according to renal function, body mass index (BMI), and New York Heart Association (NYHA) classification. Comparison studies between the 2 natriuretic peptide markers were performed. Assays for BNP were performed with a Triage reagent pack (Biosite, Inc) on an Access 2 immunoanalyzer (Beckman-Coulter); NTproBNP assays were performed with a Roche reagent pack on an Elecsys 20.10 immunoanalyzer (Roche Diagnostics). Plasma samples were collected from consecutive patients hospitalized for cardiac disorders at our institution. Nonparametric tests were used for statistical analyses. The results show that alterations of renal function had less impact on BNP (p = 0.9) than on NTproBNP concentrations (p <0.0001). BNP and NTproBNP levels were lower in obese patients with CHF (515 +/- 61 ng/L and 1652 +/- 124 ng/L, respectively) than in lean patients (900 +/- 85 ng/L and 6686 +/- 749 ng/L). Although NTproBNP levels averaged about 10 times higher than BNP levels, there was significant correlation between these 2 markers (Deming regression r2 = 0.40, IC: 0.95). In conclusion, plasma BNP and NTproBNP assays are both useful for the diagnosis of CHF and left ventricular dysfunction. However, renal function and obesity must be taken into account for clinical interpretation. These assays have good analytical performance and the choice between them depends on local preference.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Creatinine; Female; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Renal Insufficiency; Statistics, Nonparametric

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are frequently used in diagnosing and monitoring patients with heart failure. Recent studies have demonstrated that concentrations of these peptides are decreased in obese patients, but whether lower natriuretic peptide concentrations are really due to different hemodynamics is unknown. The relationship between these markers and left ventricular end diastolic pressure (LVEDP) in obesity has not been elucidated.. We examined patients undergoing cardiac catheterization who had creatinine of < 2.0, no evidence of myocardial infarction or pulmonary embolism, and no cardiac transplant. Body mass index and LVEDP were determined, and BNP and NT-proBNP obtained at the start of each case. Obesity was defined as body mass index of > or = 30 kg/m2.. Of 203 patients enrolled, 101 were obese. The groups were similar in respect to race, creatinine, cholesterol, and history of dyslipidemia and cardiomyopathy. The obese patients tended to be younger, were more likely to have diabetes and hypertension, and were less likely to have coronary artery disease. The obese patients had higher LVEDP but reduced BNP and NT-pro-BNP. The relationship between the natriuretic peptides and LVEDP was poor, with r values of < 0.1.. Obese patients have reduced concentrations of BNP and NT-proBNP compared to nonobese patients despite having elevated LVEDP. This suggests that factors other than cardiac status impact on BNP and NT-proBNP concentrations. The poor relationship between natriuretic peptide concentrations and LVEDP also suggests that these concentrations should not be considered surrogates for cardiac filling pressures or volumes.

Topics: Aged; Blood Pressure; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Osmolar Concentration; Peptide Fragments; Regression Analysis; Ventricular Function, Left

Mild stages of heart failure might be difficult to diagnose in severely obese individuals with a body mass index (BMI) >40 kg/m(2). Measurement of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is feasible for detecting cardiac impairment. The aims of our study were to measure NT-proBNP in plasma of severely obese patients and to compare the results with results for patients in different stages of manifest cardiac dysfunction.. In 61 severely obese individuals (median BMI, 43.2 kg/m(2)) and 96 nonobese patients with existing heart failure [classified into New York Heart Association (NYHA) classes I-IV], NT-proBNP was measured in the fasting condition. A medical history, physical examination, electrocardiography, blood chemistry, and chest x-ray were performed in the obese group. In addition, echocardiography was performed in the NYHA group.. In obese individuals, NT-proBNP was increased to a median of 356 (interquartile range, 221-458) pmol/L [854 (530-1099) ng/L] and was comparable (P >0.05) to the median value for NYHA I patients {289 (258-451) pmol/L [694 (619-1082) ng/L]}, but was significantly lower than in the other NYHA groups (P <0.001 for each).. The prognostic relevance of increased NT-proBNP for risk of developing cardiac insufficiency in severely obese patients needs to be further evaluated.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Obesity; Peptide Fragments; Protein Precursors

Topics: Biomarkers; Creatinine; Cytokines; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity

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

N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in the diagnosis of heart failure and ventricular dysfunction. Obesity is an independent cardiovascular risk factor. The purpose of this study was to measure NT-proBNP plasma levels in obese and non-obese subjects with heart failure and to compare levels in subjects with ischaemic and dilated aetiology. In this study, obese subjects had 63% lower NT-proBNP plasma levels than non-obese subjects (p < 0.01). In multivariate analysis, BMI was inversely associated with NT-proBNP plasma levels (p < 0.05) and a 17% decrease in natriuretic peptide levels was attributed to obesity (p < 0.036). When we analyzed data according to the aetiology of heart failure, we found that both groups (ischaemic and dilated) had a 65% decrease in NT-proBNP plasma levels in obese subjects compared to non-obese subjects.

Topics: Aged; Biomarkers; Cardiomyopathy, Dilated; Female; Heart Failure; Humans; Immunoassay; Male; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Risk Factors; Severity of Illness Index

The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass.. Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels.. In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Topics: Absorptiometry, Photon; Adult; Aged; Biomarkers; Body Composition; Body Weight; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Texas

The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases.. We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics.. Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P<0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P<0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP.. In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

Topics: Blood Pressure; Body Mass Index; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Reference Values

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

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

This investigation evaluated the relationship between obesity and B-type natriuretic peptide (BNP) in heart failure.. Obesity is a major risk factor for the development of heart failure, but the precise mechanisms remain uncertain. Physiologically, natriuretic peptides and lipolysis are closely linked.. A total of 318 patients with heart failure were evaluated between June 2001 and June 2002. Levels of BNP were compared in obese (body mass index [BMI] > or =30 kg/m(2)) and nonobese (BMI <30 kg/m(2)) patients with respect to New York Heart Association functional class and lean body weight-adjusted peak aerobic oxygen consumption. In a subset of 36 patients, plasma levels of tumor necrosis factor-alpha, interleukin-6, and soluble intercellular adhesion molecule-1 were measured.. The population's BMI was 29.4 +/- 6.6 kg/m(2); 24% were lean (BMI <25 kg/m(2)), 31% overweight (BMI > or =25 to 29.9 kg/m(2)), and 45% obese (BMI > or =30 kg/m(2)). Obese patients were younger, more often African American, and more likely to have a history of antecedent hypertension, but less likely to have coronary artery disease and with only a trend toward diabetes mellitus. Levels of BNP were significantly lower in obese than in nonobese subjects (205 +/- 22 and 335 +/- 39 pg/ml, respectively; p = 0.0007), despite a similar severity of heart failure and cytokine levels. Multivariate regression analysis identified BMI as an independent negative correlate of BNP level. There were no differences in emergency department visits, heart failure hospitalization, or death between the obese and nonobese patients at 12-month follow-up.. Our investigation indicates that a state of reduced natriuretic peptide level exists in the obese individual with heart failure.

Topics: Adult; Age Factors; Aged; Biomarkers; Body Mass Index; Creatinine; Cytokines; Female; Heart Failure; Humans; Louisiana; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Obesity; Predictive Value of Tests; Sex Factors; Statistics as Topic; Stroke Volume

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

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 relationships among B-type natriuretic peptide (BNP) levels, body mass index (BMI), and congestive heart failure (CHF) as an emergency diagnosis are unknown.. Of 1586 participants in the Breathing Not Properly Multinational Study who had acute dyspnea, 1369 (86.3%) had BNP values and self-reported height and weight. Two independent cardiologists masked to the BNP results adjudicated the final diagnosis.. Congestive heart failure was found in 46% of participants. Individuals with higher BMIs were younger and had more frequent edema on examination but were equally as likely to have CHF vs noncardiac sources of dyspnea. A nearly 3-fold difference was seen in mean +/- SD BNP values at the low and high extremes of the BMI groupings (516.7 +/- 505.9 vs 176.3 +/- 270.5 pg/mL, respectively; P< .001). The correlations between BMI and log BNP among those with and without CHF were r = -0.34 and r = -0.21, respectively (P< .001 for both). Multivariate analysis for the outcome of log BNP among a small subset with CHF (n = 62) found that Framingham score (P = .002), estimated glomerular filtration rate (P = .007), female sex (P = .03), New York Heart Association functional class (P = .09), and third heart sound (P = .08) were independent predictors. However, BMI was not found to be independently related to log BNP (P = .59).. In patients with and without CHF, BNP levels are inversely related to BMI. When considering demographics, severity of disease, and renal function, BMI is not independently related to BNP levels in a small subgroup when detailed information about CHF severity is known.

Topics: Age Distribution; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Body Mass Index; Cohort Studies; Emergency Service, Hospital; Female; Heart Failure; Humans; Incidence; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Probability; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution; Survival Analysis

Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P < 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 +/- 0.1 in ob/ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.

Topics: Animals; Apolipoproteins B; Carrier Proteins; Collagen; Diastole; Echocardiography; Fatty Acid Transport Proteins; Fatty Acids; Gene Expression; Leptin; Lipid Metabolism; Lipoprotein Lipase; Membrane Proteins; Membrane Transport Proteins; Mice; Mice, Knockout; Mice, Obese; Microscopy, Electron; Mitochondria, Heart; Myocardium; Natriuretic Peptide, Brain; Obesity; Oxidation-Reduction; Phosphatidylcholines; Phosphatidylinositols; RNA, Messenger; Systole; Triglycerides

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

The purposes of this study were to examine a new method to determine exercise intensity for obese people based on the cardiac vagal activity and to determine the effect of this approach on myocardial stress.. Forty-three middle aged obese female volunteers (age 43.7+/-6.5 y; height 1.56+/-0.05 m; body mass 66.5+/-9.3 kg; body mass index 27.3+/-2.8 kg m(2); percentage body fat 40.7+/-5.9%).. In the first experiment, 43 subjects performed a ramp exercise test on a bicycle ergometer with measurement of ECG and gas exchange parameters. In the second experiment, 11 subjects performed 45 min of constant walking exercise on a treadmill at a level corresponding to exercise intensity determined by vagal activity obtained from a ramp bicycle test. Blood pressure, endothelin 1 (ET-1), catecholamine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were measured before and after exercise.. The heart rate variability power decreased with increasing work rate, and changed little after reaching individual-specific work rate. We presumed that vagal activity disappeared at this point and that the heart rate at this exercise intensity was determined as the vagal activity threshold (T(VA)). The results showed a significant positive correlation (r=0.742, P<0.0001) between T(VA) and ventilatory threshold (VT) heart rates, although the mean heart rate of T(VA) (114.3+/-8.5 beats/min) was significantly lower (P<0.001) than that at VT (119.0+/-11.7), suggesting the cardiac vagal withdrawal occurred prior to the onset of lactate acidosis (lactic acid accumulation). Furthermore, exercise intervention experiment at T(VA) indicated that ET-1, catecholamine and BNP levels were not significantly different before and after exercise. However, ANP levels increased significantly after exercise (pre-exercise 18.6+/-5.38 vs post-exercise 44.0+/-24.87 pg/ml, P<0.001), which in turn brought about a significant post-exercise reduction in the blood pressure (SBP 117.6+/-13.7 vs 110.5+/-7.4 mmHg, P<0.05; DBP 78.6+/-6.7 vs 73.5+/-6.6 mmHg, P<0.01).. Our data suggest that it is possible to determine the exercise intensity (T(VA)) on the basis of cardiac vagal response. These results also suggest that exercise at T(VA) level is a safe exercise intensity in the light of cardiac stress, and that T(VA) may be recommended for obese people who might possess lower cardiac sympatho-vagal activity.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Electrocardiography; Endothelin-1; Ergometry; Exercise; Exercise Test; Female; Heart Rate; Humans; Middle Aged; Natriuretic Peptide, Brain; Obesity; Oxygen Consumption; Vagus Nerve

We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min).. Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days.. Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis.. The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment.. The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

Topics: Adipocytes; Adipose Tissue; Adult; Cyclic GMP; Diet, Reducing; Female; Humans; Infusions, Intravenous; Isoproterenol; Lipid Metabolism; Lipolysis; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Obesity; Women's Health

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