natriuretic-peptide--brain and Inflammation

Early detection and risk stratification of patients with heart failure (HF) are crucial to improve outcomes. Given the complexity of the pathophysiological processes of HF and the involvement of multi-organ systems in different stages of HF, clinical prognostication of HF can be challenging. In this regard, several biomarkers have been investigated for diagnosis, screening, and risk stratification of HF patients. These biomarkers can be classified as biomarkers of myocardial stretch such as B-type natriuretic peptide, biomarkers of neurohormonal activation, biomarkers of inflammation and oxidative stress and biomarkers of cardiac hypertrophy, fibrosis and remodeling. In this paper, we summarize current evidence supporting the use of selected biomarkers in HF. We review their diagnostic, prognostic and therapeutic role in the management of HF. We also discuss potential factors limiting the use of these novel biomarkers in the clinical practice and highlight the challenges of adopting a multi-biomarker strategy.

Topics: Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis

Physical training has been reported to attenuate myocardial stress and inflammation in heart failure (HF). We aimed to assess the impact of physical training on B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as biomarkers of inflammation-C-reactive protein, tumor necrosis factor α (TNF-α), and interleukins (ILs). A systematic electronic literature search was conducted up to May 2021 in PubMed, Cochrane Library, CINAHL, Embase, and SPORTDiscus to identify randomized clinical trials reporting associations between any formal physical training intervention and biomarker levels in patients with HF. Random-effects meta-analyses was used to calculate pooled correlations between physical training and blood biomarkers. Biomarker outcomes were expressed as mean difference or ratio of means and 95% confidence interval between the intervention and control groups, according to the normality of the data. A total of 38 trials were included in the final meta-analysis (2,652 randomized patients). Physical training was associated with decreased B-type natriuretic peptide (p = 0.02), NT-proBNP (p <0.01), C-reactive protein (p <0.00001), TNF-α (p = 0.03), IL-6 (p = 0.04), and IL-1β (p = 0.001). Aerobic continuous training was associated with a 35% reduction in NT-proBNP (p = 0.01); ≥150 min/week of exercise was associated with a greater reduction in TNF-α levels (p = 0.0004), and aerobic interval training was associated with lower IL-6 levels (p = 0.01). In conclusion, physical training in patients with HF is associated with beneficial effects on natriuretic peptides and biomarkers of inflammation because they were all reduced by the intervention.

Topics: Biomarkers; C-Reactive Protein; Heart Failure; Humans; Inflammation; Interleukin-6; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Tumor Necrosis Factor-alpha

The underlying mechanism for clinical and biochemical manifestations of chronic heart failure (HF) may be due in part to neurohumoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the periphery and the brain. Internet search and discussion with colleagues are the methods for this study. Since chronic HF is associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, it may be considered a brain disease. This phenomenon may be the result of an increased systemic and cerebral angiotensin II signaling because plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic HF. Activation of angiotensin II signaling in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), and area postrema (AP) may increase the release of norepinephrine, oxidative stress, and inflammation leading to increased cardiac contractility. It is possible that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. The administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity. In chronic HF, in peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity. Increased circulating angiotensin II during chronic HF may enhance the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in worsening of HF. Increased circulating angiotensin II signaling can directly act on the central nervous system via the subfornical organ and the AP to increase sympathetic outflow resulting in to neurohumoral dysfunction, resulting in to heart failure.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Baroreflex; Brain; Cardiomegaly; Chronic Disease; Heart; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Neuroimmunomodulation; Norepinephrine; Oxidative Stress; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Renin-Angiotensin System; Sympathetic Nervous System; Vagus Nerve Stimulation

Cardiac troponin (cTn) plays an essential role for assessment of outcome in acute coronary syndrome (ACS). However, the prognostic value of cTn is not absolute. In this mini-review, we summarize the evidence on the utility of established biomarkers of left-ventricular dysfunction, hemodynamic stress, inflammation, and renal dysfunction for risk prediction beyond cTn in ACS.. Only few biomarkers consistently demonstrate additive prognostic value to cTn levels. The B-type natriuretic peptides (NPs) and growth-differentiation factor-15 (GDF-15) are most promising in this regard. However, there are uncertainties regarding the role of these biomarkers for guidance of treatment decisions, and their prognostic increment to cTn levels measured with high-sensitivity assays is largely unknown. The NPs and GDF-15 provide the strongest prognostic increment to cTn levels in ACS. However, the role of these biomarkers for clinical decision-making in contemporary settings has still to be defined.

Topics: Acute Coronary Syndrome; Biomarkers; Growth Differentiation Factor 15; Humans; Inflammation; Kidney Diseases; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Troponin; Ventricular Dysfunction, Left

There is evidence that rheumatoid arthritis (RA) is associated with higher overall and cardiovascular (CV) morbidity and mortality as compared with general population. Increased prevalence of traditional risk factors and chronic inflammation, that has been recognized as independent CV risk factor, may play an important role in atherosclerosis and subsequently ischemic heart disease development. However, myocardial dysfunction as a result of chronic inflammation and secondarily myocardial fibrosis markedly participates on heart failure development. Proinflammatory cytokines, such as C-reactive protein, tumor necrosis factor alpha (TNFα), interleukins 1 and 6, that are markedly increased in RA, play a role in the acceleration of atherosclerosis as well as myocardial fibrosis development. Several studies documented that increased CV risk was associated with seropositivity, disease activity score, citrullination, and duration of RA. Early detection of heart dysfunction is based on echocardiographic detection of diastolic dysfunction resulting from myocardial inflammation and fibrosis. Some studies showed also higher prevalence of left ventricular systolic dysfunction and increased prevalence of cardiac arrhythmias as compared to non-RA population. There are still controversies on the impact of NT-proBNP in predicting cardiac impairment in RA patients. Some authors consider it to be a sensitive noninvasive predictor of subclinical CV disease in these patients and also a predictor of all-cause mortality independently on traditional CV risk factors. However, the correlation with parameters of cardiac function was confirmed only in a few studies. The impact of biological treatment on progression of atherosclerosis and heart failure is still controversial and seems to be not harmful in young patients with normal left ventricular function. The effect of biologics, especially anti-TNFα drugs, is probably related to the cardiac function before treatment. Larger prospective clinical, echocardiographic, and magnetic resonance studies are needed.

Topics: Antibodies, Blocking; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Fibrosis; Humans; Immunotherapy; Inflammation; Inflammation Mediators; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Tumor Necrosis Factor-alpha

Natriuretic peptide receptor A (NPR-A) is the receptor for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). NPR-A plays critical physiological and pathophysiological roles in several target cell and tissue system processes, such as cell growth, apoptosis, proliferation, and inflammation. Accumulating data demonstrate that NPR-A is involved in immune and inflammatory reactions and is a potential target in inflammation treatment. It is expressed in various cancer cells and is important for tumor growth. A recent study indicated that NPR-A signaling can regulate stem cell recruitment and angiogenesis. This signaling can serve as a model for studying the linkage between inflammation and tumorigenesis. In this review we highlight the mechanisms by which NPR-A affects signaling pathways involved in inflammation and cancer, and we discuss its potential as a novel target in inflammation, cancer, and cancer-related inflammation.

Topics: Apoptosis; Atrial Natriuretic Factor; Carcinogenesis; Cell Proliferation; Humans; Inflammation; Natriuretic Peptide, Brain; Neoplasms; Neovascularization, Pathologic; Receptors, Atrial Natriuretic Factor; Signal Transduction

Heart failure (HF) with preserved ejection fraction (HFPEF) is an increasingly prevalent clinical syndrome with many unresolved issues regarding diagnosis, pathophysiology, and treatment. The major pathophysiological mechanisms underlying HFPEF are known to be fibrosis and reduced ventricular compliance, and hypertension (HTN) is perhaps the most significant risk factor for the development of left ventricular diastolic dysfunction (LVDD). Inflammation is one of the earliest events in cardiac stress situations such as pressure and/or volume overload and involves elevated levels of endothelial adhesion molecules as well as increased production and release of inflammatory cytokines and chemokines in the tissue. The latter promotes the infiltration of activated inflammatory cells, particularly monocytes, into the cardiac tissue. Increased monocyte infiltration is seen in the early and late stages of HTN and HFPEF. Once inside the tissue, monocytes differentiate into macrophages and promote cardiac inflammation, tissue injury, and myocardial fibrosis. This review focuses on inflammation as the initial and primary trigger of ventricular remodelling in HTN and LVDD, affecting progression to HFPEF. The link between inflammation and b-type natriuretic peptide (BNP), a clinical marker of cardiac pressure overload which is positively associated with cardiac dysfunction and HF, is also described. Finally, current and prospective therapeutic approaches for HFPEF based on modification of the inflammatory response are reviewed.

Topics: Heart Failure; Heart Ventricles; Humans; Inflammation; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Topics: Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Autonomic Nervous System; C-Reactive Protein; Cardiac Output, Low; Catheter Ablation; Comorbidity; Defibrillators, Implantable; Echocardiography, Transesophageal; Electric Countershock; Electrocardiography; Fibrinolytic Agents; Heart Atria; Heart Conduction System; Humans; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Pacemaker, Artificial; Platelet Aggregation Inhibitors; Renin-Angiotensin System; Risk Assessment; Risk Factors; Septal Occluder Device; Stroke; Thromboembolism; Ventricular Remodeling

Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome.

Topics: Acute Disease; Amides; Benzazepines; Cardio-Renal Syndrome; Dobutamine; Fumarates; Heart Failure; Humans; Hydrazones; Inflammation; Kaplan-Meier Estimate; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Prognosis; Pyridazines; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Simendan; Therapies, Investigational; Tolvaptan

The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor (ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions of these hormones the heart contributes to the regulation of the cardiac preload and afterload. More recently, new functions for these hormones have been described including the modulation of the immune response. Plasma levels of BNP but not those of ANF, increase following an acute rejection episode of a cardiac allotransplant but return to levels pre-rejection with successful treatment. This observation constitutes the first observation leading to characterizing the interactions of BNP with the immune response. Several other pathologies with an inflammatory component are now known to be associated with an increase in the production of BNP. Such an increase is due to an increase in the transcriptional activity of the BNP gene induced by cytokines and related substances. In vitro investigations have shown that an increase in BNP directly modulates immunological activity. Inflammation and hemodynamic changes co-exist in several cardiovascular diseases and therefore it may be beneficial to measure circulating levels of both ANF and BNP as biomarkers of changes in intravascular volume and of changes in intravascular volume plus inflammation, respectively. Changes in plasma ANF, that are relatively larger than those of BNP, might be an indication of hemodynamic deterioration while important changes in circulating BNP could indicate a worsening of the inflammatory process.

Topics: Animals; Atrial Natriuretic Factor; Biomedical Research; Hemodynamics; Humans; Inflammation; Myocarditis; Myocytes, Cardiac; Natriuretic Peptide, Brain; Sepsis

Chronic obstructive pulmonary disease (COPD) can no longer be considered as a disease affecting only the lungs. Increasing evidence supports the presence of a systemic inflammatory component which is thought to provide the link between COPD and the co-morbidities commonly associated with this disease. These include cardiovascular disorders, skeletal muscle dysfunction, diabetes, and osteoporosis. The majority of current therapies for COPD have been developed to improve airway obstruction or to target airway inflammation, leaving an unmet medical need with respect to the systemic inflammatory component of COPD and its extra-pulmonary manifestations. This review describes systemic biomarkers in COPD and their relationship with both the local lung and systemic manifestations of the disease. A summary is provided of the most promising biomarkers that have been investigated in COPD and its co-morbidities. Such biomarkers may be used to assess and manage the systemic effects of COPD, and may guide future development of novel therapeutic interventions to provide a more holistic approach to treating this multi-faceted disease.

Topics: Adiponectin; Aging; Airway Remodeling; Biomarkers; C-Reactive Protein; Cachexia; Cardiovascular Diseases; CD40 Ligand; Chemokines, CC; Cytokines; Desmosine; Fibrinogen; Humans; Inflammation; Intercellular Adhesion Molecule-1; Isodesmosine; Lung Neoplasms; Matrix Metalloproteinases; Natriuretic Peptide, Brain; Osteoprotegerin; Pulmonary Disease, Chronic Obstructive; Pulmonary Surfactant-Associated Protein D; Serum Amyloid A Protein; Severity of Illness Index; Telomere; Uteroglobin

Cardiovascular (CV) clinical trials are instrumental in understanding treatment effects and offer insights into the natural progression of CV disease. Biomarkers are a critical component of patient selection, end point definition, and safety monitoring, and clinical trials provide a platform for the discovery and validation of new biomarkers that may augment the understanding of disease mechanisms, risk stratification, and/or clinical decision-making.. We review the roles that biomarkers have played in CV clinical trials and roles that CV clinical trials have played and will continue to play in the discovery and validation of biomarkers and their implementation in clinical practice. Large biobanks containing multiple specimen types are increasingly being created from patients enrolled in clinical trials, and such biobanks, when coupled with advances in molecular techniques and bioinformatics, promise to accelerate our understanding of CV disease mechanisms and to help fuel the discovery and development of novel therapeutic targets and biomarkers of risk and treatment response.. The past, present, and future of biomarkers and clinical trials have been and will remain intertwined. Biomarkers were once the workhorses of patient selection and end point definition in clinical trials; more recently, clinical trials have been the proving ground for individual biomarkers. Attention to biobanking and the application of modern informatics and molecular techniques to samples collected within clinical trials will usher in the era of stratified and personalized medicine.

Topics: Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Clinical Trials as Topic; Disease Progression; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Troponin I; Troponin T

Takotsubo cardiomyopathy (TTC) is a form of reversible acute cardiac dysfunction of uncertain pathogenesis, which occurs predominantly in postmenopausal women, often with antecedent severe stress. Systolic dysfunction most commonly affects the apex of the left ventricle. There is considerable uncertainty regarding the pathogenesis of TTC and the optimal diagnostic methodology. Acute catecholamine release may play a component role, but the regional hypokinesis is associated with an acute inflammatory process, with resultant early release of brain natriuretic peptide (BNP) and N-terminal pro-BNP. As the diagnosis of TTC has largely been a process of exclusion, there has been considerable underdiagnosis. The combination of demographics, preceding history, ECG appearances and N-terminal pro-BNP elevation may provide the basis for improved early diagnosis. Complete recovery takes at least several months, with a risk of recurrent episodes. Efforts to delineate pathogenesis, expedite diagnosis and evaluate residual disability may assist in the development of appropriate treatment regimens.

Topics: Animals; Catecholamines; Early Diagnosis; Electrocardiography; Female; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Postmenopause; Recurrence; Stress, Psychological; Takotsubo Cardiomyopathy

Acute myocarditis is an inflammatory disease of the heart muscle that may progress to dilated cardiomyopathy and chronic heart failure. A number of factors including the sex hormone testosterone, components of innate immunity, and profibrotic cytokines have been identified in animal models as important pathogenic mechanisms that increase inflammation and susceptibility to chronic dilated cardiomyopathy. The clinical presentation of acute myocarditis is non-specific and mimics more common causes of heart failure and arrhythmias. Suspected myocarditis is currently confirmed using advanced non-invasive imaging and histopathologic examination of heart tissue. However, the diverse presentations of myocarditis and the lack of widely available, safe, and accurate non-invasive diagnostic tests remain major obstacles to early diagnosis and population based research. Recent advances in the understanding of disease pathogenesis described in this review should lead to more accurate diagnostic algorithms and non-invasive tests.

Topics: Algorithms; Animals; Biomarkers; Biopsy; Cardiomyopathy, Dilated; Diagnosis, Differential; Disease Progression; Early Diagnosis; Evidence-Based Medicine; Heart Failure; Humans; Inflammation; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Sex Distribution; Troponin I; Troponin T

Hospitalization for decompensated heart failure (HF) is associated with extraordinarily high rates of morbidity and mortality. Despite its high prevalence its pathophysiologic mechanisms and future risk stratification remain poorly defined and understudied. Several clinical Risk Scores to recognize high risk patients, has been purposed in the past but they are not able to completely identify future adverse events. In this sense, laboratory biomarkers play an important role in heart failure, but there remain unanswered questions regarding optimization of their use. One of the biggest hopes for utilizing biomarker testing is to determine the level of disease severity in a manner to triage medical decisions as well as to monitor their responses. Early diagnosis is very important for a better therapy optimization and outcome improving. Indeed, identification is often difficult because of symptoms unspecificity and the lack of gold standard protocol to make diagnosis. B-type natriuretic peptide is a useful tool to confirm or rule out heart failure. Therefore, BNP is one of the most best prognostic indicator in all stages of heart failure predicting outcome in both hospitalized and outpatients. Other neurohormonal, inflammatory and metabolic markers may add complementary information to that provided by currently available B-type natriuretic peptide assays. However all specific and general laboratory parameters cannot substitute to traditional clinical evaluation but could be used in adjunction for more precise evaluation and assessment. We reviewed traditional and some of emerging biomarkers of potential clinical application in HF setting.

Topics: Algorithms; Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Neurotransmitter Agents; Stress, Physiological

Patients with chronic kidney disease (CKD) are, compared to the general population, at higher risk of cardiovascular disease (CVD), including sudden death, coronary artery disease (CAD), congestive heart failure (HF), stroke, and peripheral artery disease. The presence of CVD is independently associated with kidney function decline. Renal insufficiency is a strong and independent predictor of mortality in patients with different CKD stages. The interplay of traditional and nontraditional risk factors is complex such that risk factor profiles are different in CKD patients. Seemingly, paradoxical associations between traditional risk factors and cardiovascular outcome complicate efforts to identify real cardiovascular etiology in these patients. Additional tools are often required to aid clinical assessment of cardiovascular risk. Recently, a number of cardiovascular biomarkers were identified as predictors of outcome in CVD. These may be used to guide early diagnosis and therapy for CVD or may predict outcome in CKD. This review focuses on the potential diagnostic and prognostic use of some important new biomarkers including brain natriuretic peptide (BNP), cardiac troponins (cTns), inflammatory markers, adhesion molecules, and asymmetric dimethylarginine (ADMA) in CKD as well as those patients with end-stage renal failure.

Topics: Animals; Arginine; Biomarkers; Cardiovascular Physiological Phenomena; Cell Adhesion Molecules; Humans; Inflammation; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Renal Dialysis; Troponin

Effective management of patients with pulmonary arterial hypertension (PAH) requires comprehensive prognostic evaluation in order to determine optimal management strategies. Although a number of clinical and hemodynamic parameters linked to PAH prognosis have been identified, some are associated with significant limitations (eg, invasive techniques, subjective measures). There is a need for noninvasive and objective measures to be established that function as biomarkers for the diagnosis and assessment of disease prognosis, and that determine response to therapy in patients with PAH. Reflecting the highly complex etiology of the disease, a large number of potential biomarkers have been, and continue to be, investigated in PAH, including those reflecting right heart function, endothelial dysfunction, and markers of inflammation and second organ failure. However, it has become clear that scientifically interesting biomarkers may not necessarily be clinically useful. Of the range of biomarkers investigated in PAH to date, only brain natriuretic peptide and its N-terminal cleavage product have been included as prognostic parameters in treatment guidelines. It is unlikely that any single biomarker will provide all the relevant information required for an individual patient, and the potential for combining markers is currently of considerable interest. Future studies are required to determine the optimal combination of existing and emerging biomarkers in the clinical setting.

Topics: Biomarkers; Creatinine; Endothelium, Vascular; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prognosis; Sodium; Troponin T

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

The mortality of end-stage renal disease (ESRD) patients on dialysis remains high despite great improvement of dialysis technologies in the past decades. These patients die due to infectious diseases (mainly sepsis), cardiovascular diseases such as myocardial infarction, heart failure, stroke, and, in particular, sudden cardiac death. End stage renal disease is a complex condition, where the failure of kidney function is accompanied by numerous metabolic changes affecting almost all organ systems of the human body. Many of the biomarker characteristics of the individually affected organ systems have been associated with adverse outcomes. These biomarkers are different in patients with ESRD compared to the general population in the prediction of morbidity and mortality. Biomarker research in this field should aim to identify patients at risk for the different disease entities. Traditional biomarkers such as CRP, BNP, and troponins as well as new biomarkers such as fetuin, CD154, and relaxin were analyzed in patients on dialysis. We will include observational as well as prospective clinical trials in this review. Furthermore, we will also discuss proteomics biomarker studies. The article assess the potential diagnostic value of different biomarkers in daily clinical practice as well as their usefulness for clinical drug development in end stage renal disease patients.

Topics: alpha-2-HS-Glycoprotein; Biomarkers; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Cell Adhesion Molecules; Comorbidity; Dyslipidemias; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homocysteine; Humans; Infections; Inflammation; Interleukin-6; Kidney Failure, Chronic; Malnutrition; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proteomics; Renal Replacement Therapy; Troponin T

Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart failure. It typically develops during the last month of, and up to 6 months after, pregnancy in women without known cardiovascular disease. The present position statement offers a state-of-the-art summary of what is known about risk factors for potential pathophysiological mechanisms, clinical presentation of, and diagnosis and management of PPCM. A high index of suspicion is required for the diagnosis, as shortness of breath and ankle swelling are common in the peripartum period. Peripartum cardiomyopathy is a distinct form of cardiomyopathy, associated with a high morbidity and mortality, but also with the possibility of full recovery. Oxidative stress and the generation of a cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of PPCM. In this regard, pharmacological blockade of prolactin offers the possibility of a disease-specific therapy.

Topics: Antihypertensive Agents; Cardiology; Cardiomyopathies; Cathepsin D; Europe; Female; Humans; Incidence; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Postpartum Period; Pregnancy; Pregnancy Complications; Prognosis; Prolactin; Risk Factors; Societies, Medical

Although assessment of traditional coronary heart disease risk factors can often stratify individuals into low- or high-risk categories, additional means are needed to more precisely classify people clinically defined as intermediate-risk, to guide the intensity of risk-reducing therapies. The recognition that inflammatory pathways are important in the progression of atherosclerosis and its complications has prompted investigation to identify circulating risk markers that may be useful in risk stratification. This article summarizes recent studies on the current use of an emerging group of inflammatory markers: soluble CD-40 ligand, interleukin-18, myeloperoxidase, B-type natriuretic peptides, secretory phospholipase A(2), lipoprotein-associated phospholipase A(2), and C-reactive protein. The demonstration that lowering C-reactive protein along with low-density lipoprotein cholesterol with statins reduces events beyond cholesterol lowering alone suggests that titration of therapies using other emerging inflammatory markers may further reduce the toll of atherosclerosis in adult populations.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; C-Reactive Protein; CD40 Ligand; Cholesterol, LDL; Coronary Artery Disease; Disease Progression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Interleukin-18; Natriuretic Peptide, Brain; Peroxidase; Phospholipases A2, Secretory; Risk Assessment; Risk Factors

Despite newer neuroimaging techniques, timely and accurate diagnosis of acute stroke remains a significant challenge. The ability to identify stroke patients rapidly using a biologic biomarker would be highly beneficial. Inflammation following stroke is one physiologic mechanism that has been studied extensively in biomarker research. Several emerging inflammatory biomarkers have been identified and may be useful to diagnosis stroke, to predict the evolution of stroke, and to predict hemorrhagic transformation, particularly with the administration of thrombolytic therapy. Many challenges must be overcome before application to clinical practice can be recommended. Nevertheless, emerging inflammatory biomarkers demonstrate considerable promise, particularly as part of a multiple biomarker strategy, and significant improvement in stroke diagnosis, clinical management, and outcomes may be realized.

Topics: Acute Disease; Biomarkers; Cytokines; Early Diagnosis; Humans; Inflammation; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Nerve Growth Factors; Prognosis; Reactive Oxygen Species; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Sensitivity and Specificity; Stroke; Time Factors; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

Valvular heart disease (VHD) is characterized by an ongoing, inflammatory cellular response which results in a left ventricular hemodynamic stress change in response to valvulopathy. The current inflammatory hypothesis suggests that as the heart valve disease progresses the inflammatory cytokine response is activated causing continuation of deleterious effects on the heart and vasculature. This can lead to progression of heart failure and left ventricular dysfunction. Over the last 10 years, a number of biologically active molecules, termed biomarkers, have been discovered in VHD. These can be used to detect the progression and pathogenesis of heart failure and to assess the severity of inflammation (e.g., C-reactive protein). Brain natriuretic peptide (BNP) can diagnose underlying cardiac systolic and diastolic dysfunction. In high-risk patients BNP is also considered to be a useful tool for assisting in the diagnosis and monitoring the progression of VHD. Patients with symptomatic VHD benefit from aortic valve surgery; however, management in the absence of symptoms remains challenging. While the lack of symptoms can delay aortic valve replacement, unselected premature aortic valve replacement may be associated with unbalanced risks of cardiac surgery. This review summarizes the current and emerging clinical and potential research application of specific biomarkers of VHD.

Topics: Biomarkers; C-Reactive Protein; Disease Progression; Heart Failure; Heart Valve Diseases; Humans; Inflammation; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Current cardiovascular risk prediction models incorporate traditional risk factors to estimate 10-year cardiovascular risk. Numerous blood-based biomarkers have been identified that are associated with increased cardiovascular risk after adjusting for traditional risk factors. Many of these biomarkers, alone or in combination, have been incorporated into risk prediction models to determine whether their addition increases the model's predictive ability. We review the recently published literature on blood-based biomarkers and examine whether incorporating these markers may improve clinical decision making.

Topics: Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cystatin C; Humans; Inflammation; Lipoproteins; Models, Theoretical; Natriuretic Peptide, Brain; Risk Factors; Time Factors; Troponin

The natriuretic peptide system includes three known peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They contribute to the regulation of cardiovascular homeostasis through diuretic, natriuretic, and vasodilatory properties. Among them, ANP has received particular attention because of its effects on blood pressure regulation and cardiac function. Although the potential for its therapeutic application in the treatment of hypertension and heart failure has been evaluated in several experimental and clinical investigations, no pharmacological approach directly targeted at modulation of ANP levels has ever reached the stage of being incorporated into clinical practice. Recently, ANP has also received attention as being a possible cardiovascular risk factor, particularly in the context of hypertension, stroke, obesity, and metabolic syndrome. Abnormalities in either peptide levels or peptide structure are thought to underlie its implied role in mediating cardiovascular diseases. Meanwhile, BNP has emerged as a relevant marker of left ventricular (LV) dysfunction and as a useful predictor of future outcome in patients with heart failure. This review deals with the major relevant findings related to the cardiovascular and metabolic effects of natriuretic peptides, to their potential therapeutic use, and to their role in mediating cardiovascular diseases.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Fibrosis; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

Cardiovascular disease is a significant cause of morbidity and mortality, making cardiovascular prevention an important public health goal. The use of cardiac biomarkers represents a potential, noninvasive method to identify asymptomatic individuals who are most likely to develop cardiovascular disease. Several known biomarkers predict cardiovascular risk above and beyond conventional risk factors. Nonetheless, available evidence suggests that current biomarkers do not have sufficient sensitivity or specificity to justify widespread use for cardiovascular risk prediction. New developments in molecular biology and genetics may allow the identification of additional biomarkers, likely acting via different pathways, to achieve this goal.

Topics: Albuminuria; Animals; Area Under Curve; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors

Topics: Biomarkers; C-Reactive Protein; Cytokines; Fatty Acid-Binding Proteins; Heart Failure; Humans; Inflammation; Myosin Light Chains; Natriuretic Peptide, Brain; Norepinephrine; Nurse's Role; Nursing Assessment; Peroxidase; Prognosis; Risk Assessment; Sensitivity and Specificity; Troponin

After brain natriuretic peptide (BNP) was isolated in 1988, rapid progress was made in cloning its cDNA and gene, facilitating studies of tissue-specific expression and molecular regulation of gene expression. This review focuses on the molecular determinants of regulation of the rat and human BNP genes, including signaling pathways that impact on changes in gene expression and cis regulatory elements responsive to these signaling pathways. For both rat and human genes, elements in the proximal promoter (-124 to -80), including GATA, MCAT, and AP-1-like, have been shown to contribute to basal and inducible regulation. More distal elements in the human BNP gene respond to calcium signals (an NF-AT site at -927), thyroid hormone (a thyroid-responsive element at -1000), and mechanical stretch (shear stress-responsive elements at -652 and -162). Understanding how BNP is regulated by signaling molecules that are activated in the hypertrophied and ischemic heart should be useful in understanding the underlying pathology. This may lead to therapeutic strategies that prevent hypertrophy while allowing for the beneficial effects of BNP production.

Topics: Animals; DNA, Complementary; Exons; Gene Expression Regulation; Humans; Inflammation; Models, Biological; Models, Genetic; Mutation; Myocardial Ischemia; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Protein Processing, Post-Translational; Rats; Signal Transduction; Tissue Distribution

Since the first biomarker of myocardial necrosis was described in 1954, cardiac-specific biomarkers have been increasingly identified. This, coupled with dramatic evolution in assay technology and resultant highly sensitive assays, has rendered a remarkable transformation in the medical use of biomarkers. Initially used to aid in diagnosis of myocardial infarction, newer biomarkers of inflammation, plaque instability, and ischemia may complement biomarkers of necrosis by providing tools to diagnose impending myocardial necrosis before irreversible damage occurs, and offering additional information for risk stratification. Importantly, biomarkers of different processes may be combined to enhance risk stratification above that of any single marker.

Topics: Angina, Unstable; Biomarkers; C-Reactive Protein; CD40 Ligand; Humans; Inflammation; Interleukins; Myocardial Infarction; Myocardial Ischemia; Myoglobin; Natriuretic Peptide, Brain; Necrosis; Peroxidase; Pregnancy-Associated Plasma Protein-A; Risk Assessment; Troponin

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

Topics: Acute Disease; Angina, Unstable; Biomarkers; Coronary Disease; Heart Failure; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Necrosis; Prognosis; Risk Assessment

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

Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.. The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.. Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.. In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.

Topics: Atrial Fibrillation; Biomarkers; Cystatin C; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Interleukin-6; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Troponin T

Patients with heart failure (HF) and coronary artery disease (CAD) have a high risk for cardiovascular (CV) events including HF hospitalization, stroke, myocardial infarction (MI) and sudden cardiac death (SCD). The present study evaluated associations of proteomic biomarkers with CV outcome in patients with CAD and HF with reduced ejection fraction (HFrEF), shortly after a worsening HF episode. We performed a case-control study within the COMMANDER HF international, double-blind, randomized placebo-controlled trial investigating the effects of the factor-Xa inhibitor rivaroxaban. Patients with the following first clinical events: HF hospitalization, SCD and the composite of MI or stroke were matched with corresponding controls for age, sex and study drug. Plasma concentrations of 276 proteins with known associations with CV and cardiometabolic mechanisms were analyzed. Results were corrected for multiple testing using false discovery rate (FDR). In 485 cases and 455 controls, 49 proteins were significantly associated with clinical events of which seven had an adjusted FDR < 0.001 (NT-proBNP, BNP, T-cell immunoglobulin and mucin domain containing 4 (TIMD4), fibroblast growth factor 23 (FGF-23), growth differentiation factor-15 (GDF-15), pulmonary surfactant-associated protein D (PSP-D) and Spondin-1 (SPON1)). No significant interactions were identified between the type of clinical event (MI/stroke, SCD or HFH) and specific biomarkers (all interaction FDR > 0.20). When adding the biomarkers significantly associated with the above outcome to a clinical model (including NT-proBNP), the C-index increase was 0.057 (0.033-0.082), p < 0.0001 and the net reclassification index was 54.9 (42.5 to 67.3), p < 0.0001. In patients with HFrEF and CAD following HF hospitalization, we found that NT-proBNP, BNP, TIMD4, FGF-23, GDF-15, PSP-D and SPON1, biomarkers broadly associated with inflammation and remodeling mechanistic pathways, were strong but indiscriminate predictors of a variety of individual CV events.

Topics: Atrial Remodeling; Biomarkers; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Proteomics; Stroke; Stroke Volume; Ventricular Dysfunction, Left

This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arterial Pressure; Biomarkers; Biphenyl Compounds; Drug Combinations; Drug Therapy, Combination; Female; Heart Failure; Hormone Antagonists; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Pulmonary Artery; Stroke Volume; Tetrazoles; Treatment Outcome; Troponin T; Valsartan

Coronary heart disease (CHD) is a clinical syndrome caused by coronary atherosclerosis (AS) or functional changes in coronary arteries. We have previously reported that astragaloside IV (in astragalus) and tanshinone IIA (in Salvia miltiorrhiza) improve myocardial ischemic injury.. This study will employ the randomized, blinded, prospective, single-center experiments approach. Briefly, a total of 160 eligible patients will be equally randomized into three treatment groups and placebo control groups. Patients will receive appropriate treatments every 24 h for seven days after enrollment and followed up for 28 days. The main evaluation indicators will be cell count, serum high-sensitivity C-reactive protein (hs-CRP) level, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor (TNF)-α, oxidized low density lipoprotein (OX-LDL), angina grade, and Traditional Chinese Medicine (TCM) symptom changes scale. Secondary indicators to be evaluated will include B-type natriuretic peptide (BNP) levels, troponin (cTn), muscle enzyme isoenzyme (CK-MB), heart-type fatty acid binding protein (H-FABP), liver and renal functions, as well as blood coagulation. Close monitoring of adverse events during the trial will also be conducted.. This randomized controlled trial of Chinese herbal extracts for the treatment of coronary heart disease will generate results that are expected to provide valuable clinical evidence to inform future development of therapies towards management of CHD.. China Clinical Trial Registration Center, ChiCTR1900021590. Registered on 28 February 2019.

Topics: Astragalus propinquus; Biomarkers; C-Reactive Protein; Coronary Disease; Cytokines; Drugs, Chinese Herbal; Humans; Inflammation; Injections; Natriuretic Peptide, Brain; Prospective Studies; Randomized Controlled Trials as Topic; Salvia miltiorrhiza

The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease.. We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease.. The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30-2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76-3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12-2.44) for NT-proBNP, and 1.65 (95% CI, 1.13-2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0-4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37-1.77) per 1-unit increase in the score.. Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.

Topics: Aged; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Death, Sudden, Cardiac; Female; Heart Injuries; Humans; Inflammation; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin I

Elevated C-reactive protein (CRP) is associated with adverse outcomes in heart failure (HF) patients. Beta-blocker therapy may lower CRP levels.. To assess if the changes of high-sensitivity (hs) CRP levels in HF patients over 12-week titration with beta-blockers correlate with functional capacity, plasma hs-CRP levels were measured in 488 HF patients [72.1 ± 5.31 years, LVEF 40% (33/50)]. Hs-CRP, NT-proBNP and 6-min-walk-test (6MWT) were assessed at baseline and at week 12. Patients were divided based on hs-CRP changes (cut-off > 0.3 mg/dl) into low-low (N = 225), high-high (N = 132), low-high (N = 54), high-low (N = 77) groups. At baseline, median hs-CRP concentration was 0.25 (0.12/0.53) mg/dl, NT-proBNP 551 (235/1455) pg/ml and average 6MWT distance 334 ± 105 m. NT-proBNP changes were significantly different between the four hs-CRP groups (P = 0.011). NT-proBNP increased in the low-high group by 30 (- 14/88) pg/ml and decreased in the high-low group by - 8 (- 42/32) pg/ml. 6MWT changes significantly differed between groups [P = 0.002; decrease in the low-high group (- 18 ± 90 m) and improvement in the low-low group (24 ± 62 m)].. After beta-blocker treatment, hs-CRP levels are associated with functional capacity in HF patients. Whether this represents a potential target for intervention needs further study.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aging; Biomarkers; C-Reactive Protein; Double-Blind Method; Exercise Tolerance; Female; Health Status; Heart Failure; Humans; Inflammation; Inflammation Mediators; Male; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Treatment Outcome; Walk Test

As cardiac troponins emerge as prognostic markers in atrial fibrillation (AF), it is important to identify mechanisms initiating and perpetuating cardiac troponin release, including its relations to other circulating biomarkers, in AF populations. We studied associations between high-sensitivity troponin I (hs-TnI) and markers representing myocardial wall tension, inflammation and haemostasis in persistent AF.. In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion for persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Associations between baseline levels of hs-TnI and other biomarkers were investigated by bivariate non-parametric correlations (Spearman's correlation coefficient denoted r. Hs-TnI correlated weakly with biomarkers representing myocardial wall tension, inflammation and haemostasis in persistent AF. The lack of any strong correlation between hs-TnI and the investigated biomarkers is in concert with the idea that hs-TnI release is an independent process parallel to other pathophysiological mechanisms associated with AF.

Topics: Aged; Antihypertensive Agents; Atrial Fibrillation; Benzimidazoles; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Double-Blind Method; E-Selectin; Electric Countershock; Female; Fibrin Fibrinogen Degradation Products; Hemostasis; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Tetrazoles; Tissue Plasminogen Activator; Troponin I; Vascular Cell Adhesion Molecule-1

Psychological constructs are associated with cardiovascular health, but the biological mechanisms mediating these relationships are unknown. We examined relationships between psychological constructs and markers of inflammation, endothelial function, and myocardial strain in a cohort of post-acute coronary syndrome (ACS) patients.. Participants (N = 164) attended study visits 2 weeks and 6 months after ACS. During these visits, they completed self-report measures of depressive symptoms, anxiety, optimism, and gratitude; and blood samples were collected for measurement of biomarkers reflecting inflammation, endothelial function, and myocardial strain. Generalized estimating equations and linear regression analyses were performed to examine concurrent and prospective relationships between psychological constructs and biomarkers.. In concurrent analyses, depressive symptoms were associated with elevated markers of inflammation (interleukin-17: β = .047; 95% confidence interval [CI] = .010-.083]), endothelial dysfunction (endothelin-1: β = .020; 95% [CI] = .004-.037]), and myocardial strain (N-terminal pro-B-type natriuretic peptide: β = .045; 95% [CI] = .008-.083]), independent of age, sex, medical variables, and anxiety, whereas anxiety was not associated with these markers in multivariable adjusted models. Optimism and gratitude were associated with lower levels of markers of endothelial dysfunction (endothelin-1: gratitude: β = -.009; 95% [CI] = -.017 to - .001]; optimism: β = -.009; 95% [CI] = -.016 to - .001]; soluble intercellular adhesion molecule-1: gratitude: β = -.007; 95% [CI] = -.014 to - .000]), independent of depressive and anxiety symptoms. Psychological constructs at 2 weeks were not prospectively associated with biomarkers at 6 months.. Depressive symptoms were associated with more inflammation, myocardial strain, and endothelial dysfunction in the 6 months after ACS, whereas positive psychological constructs were linked to better endothelial function. Larger prospective studies may clarify the directionality of these relationships.. Clinicaltrials.gov identifier NCT01709669.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Depression; Endothelin-1; Female; Follow-Up Studies; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-17; Male; Middle Aged; Natriuretic Peptide, Brain; Optimism; Peptide Fragments

Heart failure can be associated with inflammation but it is unclear if inflammation is directly related to hemodynamic worsening or is an independent pathway. Our aim was to investigate inflammation and mechanical stress using serial measurements of biomarkers in acute and chronic heart failure with reduced ejection fraction (AHF and CHF).. The following biomarkers were measured on admission, at discharge and one month after discharge: B-type natriuretic peptide (BNP), high-sensitivity C-Reactive protein (hsCRP), Tumour Necrosis Factor alpha (TNFα), interleukin 6 (IL6), myeloperoxidase (MPO), suppression of tumorigenicity 2 (ST2), mid-regional pro-adrenomedullin (MR-proADM), galectin 3 (Gal3), Growth differentiating factor 15 (GDF15) and procalcitonin (PCT).. In control CHF group (n=20, 69±11y, NYHA 1-2), most biomarker levels were low and stable over time. In AHF (n=55, 71±14y), BNP, ST2 and GDF15 levels were highly increased on admission and then decreased rapidly with clinical improvement; BNP, ST2 and GDF15 levels were statistically correlated (r=0.64, 0.46 and 0.39; p<0.001 for both). Both hsCRP, MPO, TNFα and Gal3 levels were increased in most AHF patients (70, 56, 83 and 98% respectively) with poor change over time. HsCRP, MPO and TNFα levels were correlated. IL6, MR-proADM and PCT levels were slightly increased, without change over time. Highest quartiles of BNP and ST2 were associated with death or readmission at one year (HR 2.33 [95CI 1.13-4.80] and 2.42 [1.27-4.60]).. AHF is associated with systemic inflammation. This inflammatory response continued up to one month after discharge despite normalisation of mechanical stress-related markers.

Topics: Adrenomedullin; Aged; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; Heart Failure; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume

Implantable cardioverter-defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.. We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT-).. Sixty-three patients were enrolled, 40 in the DFT+ group and 23 in the DFT- group. Average levels of troponin I, hsCRP, Calprotectin, N-terminal pro B-type natriuretic peptide (NTproBNP), and sFas increased by >50% after cardiac device implantation compared to baseline. Increase in troponin never exceeded the 50-fold upper limit of normal (2 ng/mL). Troponin trended higher in the DFT+ group at 8 hours (median 0.18 ng/mL, interquartile range [IQR] 0.11-0.48) versus the DFT- group (0.10 ng/mL, IQR 0.06-0.28, P = 0.0501); NTproBNP had a similar trend (P = 0.0581). sFas significantly increased in the DFT+ group from baseline (median 4663 pg/mL, IQR 2908-5679) to 24 hours (5039 pg/mL, IQR 3274-6261; P = 0.0338) but not in the DFT- group (P = 0.4705).. DFT testing is associated with acutely increased plasma levels of troponin and sFas, a biomarker of apoptosis, along with a trend toward higher NTproBNP.

Topics: Acute Disease; Aged; Apoptosis; Biomarkers; Defibrillators, Implantable; fas Receptor; Heart Failure; Heart Injuries; Humans; Inflammation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Troponin I

Vascular inflammation plays a key role in the development of atherosclerosis and acute coronary syndrome (ACS), and pentraxin 3 (PTX3) is one of several novel, promising markers of inflammation. In addition, D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. The present study assesses the prognostic utility of these two biomarkers as compared to high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP), in addition to conventional clinical risk factors for coronary heart disease in patients with suspected ACS.. Chest pain patients with suspected ACS (n = 871) were consecutively included in a prospective, observational study with a follow-up time of 84 months.. At 7-year follow-up, 332 patients had died and 203 had suffered an adverse troponin T-positive, non-fatal cardiac event. In the multivariate analysis, levels of PTX3 above 5.88 ng/mL (median) and D-dimer above 436 µg/L (lower limit upper quartile) independently predicted mortality (HR 1.60 [95% CI 1.10-2.33]; p = 0.014 and HR 1.83 [95% CI 1.20-2.78]; p = 0.005, respectively). Also, BNP levels above 310.75 pg/mL (lower limit upper quartile) (HR 2.16 [95% CI 1.37-3.42]; p = 0.001), but not hsCRP, independently predicted mortality. Only hsCRP and BNP also predicted future myocardial infarction (HR 1.59 [95% CI 1.05-2.40]; p = 0.029 and HR 1.91 [95% CI 1.10-3.31]; p = 0.021, respectively).. High levels of PTX3, D-dimer and BNP were found to be independent, long-term predictors of all-cause mortality in chest pain patients with a suspected ACS. hsCRP and BNP also predicted future myocardial infarction.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; C-Reactive Protein; Cause of Death; Enzyme-Linked Immunosorbent Assay; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Immunoturbidimetry; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Prognosis; Prospective Studies; Serum Amyloid P-Component; Survival Rate; Time Factors

Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients.. A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial. The effect of tocilizumab on cardiac biomarkers was determined using stored serum (baseline and 24 weeks) in recipients of tocilizumab (8 mg/kg every 4 weeks plus DMARDs; n = 225) or placebo (every 4 weeks plus DMARDs; n = 132).. Median NT-proBNP and hsTnT concentrations at baseline were 100 pg/ml and 5.7 pg/ml, respectively. NT-proBNP decreased in both study arms (median at 24 weeks 77 pg/ml in the placebo arm, 79 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms), and decreased to a similar extent comparing study arms (tocilizumab effect: -5.5%, p=0.55). hsTnT also decreased in both study arms (median at 24 weeks 3.1 pg/ml in the placebo arm, 4.4 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms). The extent of the reduction in hsTnT was greater in the placebo group (tocilizumab effect: +23.3%, p=0.002). Change in NT-proBNP, but not hsTnT, correlated modestly with change in CRP (r = 0.17, p=0.013).. These data argue against a rapid preferential benefit of IL-6 blockade on these specific surrogate markers of cardiovascular risk, but may be consistent with a general cardiovascular benefit of improved RA treatment. CLINICAL TRIALS.. NCT00106574.

Topics: Aged; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Interleukin-6; Troponin T

To evaluate the effects of canrenone compared to placebo on blood pressure control, some non-conventional biomarkers in cardiovascular stratification, and on metalloproteinases in patients affected by metabolic syndrome.. A total of 156 Caucasian patients were treated with placebo or canrenone, 50 mg once a day, for 3 months and then 50 mg twice a day, till the end of the study. We evaluated: systolic (SBP) and diastolic blood pressure (DBP), body weight, body mass index (BMI), fasting plasma glucose (FPG), lipid profile, plasma aldosterone, creatinine, potassium, brain natriuretic peptide (BNP), metalloproteinases 2 and 9 (MMP-2 and -9), lipoprotein (a) (Lp(a)), and serum myeloperoxidase (MPO).. We observed a significant decrease of SBP and DBP in the canrenone group compared to baseline. Canrenone gave a significant decrease of MMP-2 and -9, Lp(a), and MPO compared to baseline, not observed with placebo. Plasma aldosterone, but not BNP, decreased with canrenone, both compared to baseline and to placebo.. Canrenone seems to be effective in reducing blood pressure in patients with metabolic syndrome. Moreover, canrenone seems also to improve MPO, Lp(a), and metalloproteinases in these patients.

Topics: Aged; Aldosterone; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Canrenone; Creatine; Double-Blind Method; Fasting; Female; Humans; Inflammation; Lipids; Lipoproteins; Male; Metabolic Syndrome; Metalloproteases; Middle Aged; Natriuretic Peptide, Brain; Peroxidase; Potassium; White People

Regular exercise is recommended to improve outcomes in patients with heart failure. Exercise is known to decrease inflammation and thought to decrease myocardial stress; however, studies of exercise in heart failure have had mixed results on levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP). A multimarker analysis may help to identify distinct subgroups of patients who respond to exercise. Our primary study objective was to identify common and distinct patterns of change in hsCRP and NT-proBNP and to quantify the influence of exercise therapy on the observed patterns of change.. NT-proBNP and hsCRP were assessed in a random sample of 320 participants from the biomarker substudy of HF-ACTION, a randomized clinical trial of exercise training versus usual care in patients with stable and chronic heart failure. Growth mixture modeling was used to identify unique biomarker patterns over 12 months. Three statistically independent and clinically meaningful biomarker patterns of NT-proBNP and hsCRP were identified. Two patterns were combined and compared with the "low/stable" pattern, which was characterized by the lowest levels of NT-proBNP and hsCRP over time. Participants who were taking a loop diuretic and had hypertension or ischemic etiology were ∼2 times as likely to be in the "elevated/worsening" biomarker pattern. Participants randomized to the exercise intervention were less likely to be in the elevated/worsening pattern of NT-proBNP and hsCRP (relative risk ratio 0.56, 95% confidence interval 0.32-0.98; P = .04).. Exercise therapy was protective for reducing the frequency of membership in the elevated/worsening biomarker pattern, indicating that exercise may be helpful in delaying the progression of heart failure.

Topics: Biomarkers; C-Reactive Protein; Exercise Test; Exercise Therapy; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Treatment Outcome

Administration of a loading dose of atorvastatin 80 mg/d has been shown to be beneficial in patients with stable coronary artery disease and acute coronary syndromes. However, little is known about the impact and mechanism behind the beneficial effects of loading-dose atorvastatin treatment before percutaneous coronary intervention (PCI), especially for those patients experiencing cardiovascular inflammation in ST-segment elevation myocardial infarction (STEMI).. The goal of this randomized clinical study was to investigate whether, before emergency PCI, administration of loading-dose atorvastatin therapy in STEMI patients inhibits inflammation and improves cardiac function during 24 weeks of follow-up.. A total of 102 STEMI patients were enrolled into 3 groups: group A (n = 32) received 80 mg of atorvastatin before emergency PCI, post-PCI follow-up atorvastatin 40 mg for 4 weeks, and atorvastatin 20 mg for 20 weeks; group B (n = 32) received no pre-PCI loading dose of atorvastatin but did receive atorvastatin 40 mg for 4 weeks and then atorvastatin 20 mg for 20 weeks; and group C (n = 38) received only post-PCI atorvastatin 20 mg for 24 weeks.. No differences were found in baseline demographic and angiographic characteristics among the 3 groups. Patients in group A had the lowest plasma levels of high-sensitivity C-reactive protein (hs-CRP), B-type natriuretic peptide (BNP), and matrix metalloproteinase type 9 (MMP-9) (P < 0.05). Patients in group A also showed improvement in heart performance, with significant increases in their left ventricular ejection fraction. To a lesser extent, group B displayed reductions in the plasma levels of hs-CRP, BNP, and MMP-9 at later time points (P < 0.05). Compared with those in group C, patients in group B also exhibited significant improvement in left ventricular ejection fraction (P < 0.05).. Loading-dose atorvastatin therapy before emergency PCI reduced the inflammatory response and myocardial dysfunction in these STEMI patients by lowering hs-CRP, BNP, and MMP-9. Pre-PCI loading-dose atorvastatin treatment may help prevent inflammatory response and improve cardiac function in patients with acute coronary syndromes undergoing emergency PCI. ClinicalTrials.gov identifier: NCT01334671.

Topics: Aged; Atorvastatin; C-Reactive Protein; Combined Modality Therapy; Echocardiography; Female; Heptanoic Acids; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Prospective Studies; Pyrroles; 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

Renin-angiotensin-aldosterone system (RAAS) blockade may reduce levels of biomarkers of chronic low-grade inflammation and endothelial dysfunction. We investigated the effect of spironolactone added to standard RAAS blockade on these biomarkers in an analysis of four original studies.. The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabetic patients with micro- or macroalbuminuria treated with angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB), and randomised to additional treatment with spironolactone 25 mg and placebo daily for 60 days.. Changes in inflammatory (hsCRP, s-ICAM, TNFα, IL-6, IL-8, Serum amyloid A, IL1β), endothelial dysfunction (sE-selectin, s-ICAM1, s-VCAM1, VWF, p-selectin, s-thrombomodulin) and NT-proBNP after each treatment period.. During spironolactone treatment, u-albumin excretion rate was reduced from 605 (411-890) to 433 (295-636) mg/24 h, as previously reported. Markers of inflammation and endothelial dysfunction did not change; only changes in NT-proBNP (reduced by 14%, p=0.05) and serum amyloid A (reduced by 62%, p=0.10) were borderline significant.. Our results indicate that the renoprotective effect of spironolactone when added to RAAS blockade is not mediated through anti-inflammatory pathways since markers of inflammation and endothelial dysfunction are not affected during treatment.

Topics: Albuminuria; Biomarkers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Endothelium; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spironolactone

Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown.. In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI).. Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value.. Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.

Topics: Aged; Antibodies, Monoclonal, Humanized; Biomarkers; C-Reactive Protein; Canada; Cause of Death; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Germany; Heart Failure; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Prognosis; Shock, Cardiogenic; Single-Chain Antibodies; Sweden; United States

Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P < 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P < 0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P < 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; Double-Blind Method; Female; Gene Expression Regulation; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments

We tested the hypothesis that adding an ultrafiltration session per week may improve brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels and left ventricular function in hypervolemic hemodialysis patients.. Twenty-six patients (18 male, 8 female; mean age 57.2 ± 12.7 years) who had high BNP and CRP levels and interdialytic weight gain (IDWG) were recruited for the study. Patients were randomly allocated to one of two groups, namely the supplementary ultrafiltration (sUF) group (n = 13), who had additional ultrafiltrations for 8 weeks, and the regular hemodialysis (rHD) group (n = 13), who continued regular dialysis treatments.. There were significant decreases in mean CRP and BNP levels and mean arterial blood pressure and significant improvements in left ventricular function in the sUF group, with no changes in the rHD group. Higher IDWG was observed in the rHD group compared to the sUF group after 8 weeks.. sUF may be effective in reducing inflammatory burden and improving cardiac function.

Topics: Adult; Aged; C-Reactive Protein; Echocardiography; Female; Hemofiltration; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Ventricular Dysfunction, Left; Weight Gain

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program.. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that.. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-γ [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively].. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Topics: Acute Disease; Adult; Aged; Biomarkers; Chronic Disease; Coronary Artery Disease; Cytokines; Exercise; Exercise Test; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain

Strenuous exercise induces significant increases in cardiac biomarkers. However, it is still unclear whether this is caused by cardiomyocyte necrosis or secondary mechanisms such as ischemia, cardiac energy deficiency, increased inflammation, or renal dysfunction.. Therefore, we investigated cardiac biomarkers (high-sensitive cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (h-FABP)), inflammation markers (high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10, tumor necrosis factor-α), and renal function (cystatin C) in 102 healthy men age 42 ± 9 yr before and 0, 24, and 72 h after a marathon.. Kinetics of hs-cTnT revealed a peak immediately after the race (V3) that decreased rapidly to pretest values within 72 h (V5) (median (interquartile range) = 31.07 (19.25-46.86) ng·L(-1) at V3 and 3.61 (3.20-6.70) ng·L(-1) at V5, P < 0.001). NT-proBNP and h-FABP kinetics showed a similar pattern (NT-proBNP = 92.6 (56.9-149.7) ng·L(-1) at V3 and 34.9 (21.7-54.5) ng·L(-1) at V5; h-FABP = 44.99 (32.19-64.42) μg·L(-1) at V3 and 7.66 (5.64-10.60) μg·L(-1) at V5; always P < 0.001). Proinflammatory markers, such as IL-6 and hs-CRP, and renal dysfunction were significantly augmented immediately after the race (before the race compared with maximum after the race: IL-6 = 15.5-fold, hs-CRP = 28-fold, cystatin C = 1.22-fold, all P < 0.001). These increases were not related to the increase of hs-cTnT. Similarly, training history, finishing time, and exercise intensity were not associated with changes of hs-cTnT.. Cardiac biomarkers were increased immediately after a marathon race. Interestingly, values returned to normal levels within 72 h. These kinetics with a sharp peak indicate that cardiac necrosis during marathon running seems very unlikely but may be explained by altered myocyte metabolism.

Topics: Adult; C-Reactive Protein; Cystatin C; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Endurance; Running; Troponin T; Young Adult

Sleep-disordered breathing (SDB) is thought to be a state of inflammation caused by hypoxic stress. Whether adaptive servo ventilation (ASV) attenuates the inflammatory response and improves the cardiac function of patients with congestive heart failure (CHF) accompanied by SDB was not been investigated.. Seventeen inpatients with New York Heart Association (NYHA) II or III underwent polysomnography. There was a positive correlation between the apnea hypopnea index and high-sensitivity C-reactive protein (hs-CRP) level (r=0.753, P=0.016). The patients were divided into ASV (n=10) and non-ASV groups (n=7), and CHF-parameters were measured before and after ASV treatment. Improvement was noted for the NYHA class in the ASV group but not in the non-ASV group. In contrast to the non-ASV group, the level of brain natriuretic peptide (BNP), ejection fraction, and hs-CRP levels in the ASV group significantly improved (BNP, 212.1 ± 181.2 to 77.3 ± 54.0 pg/ml [P<0.05]; ejection fraction, 43.5 ± 6.4 to 53.3 ± 6.1% [P=0.002]; hs-CRP, 0.85 ± 0.58 to 0.21 ± 0.19 mg/dl, [P=0.008]). The increase in ejection fraction was correlated with a decrease in the hs-CRP level (r=-0.753, P=0.001).. Anti-inflammatory effects of ASV are important contributors for improving cardiac function in patients with CHF accompanied by SDB. 

Topics: Aged; C-Reactive Protein; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Positive-Pressure Respiration; Sleep Apnea Syndromes; Treatment Outcome

We have demonstrated that an increased peak serum C-reactive protein (CRP) level after acute myocardial infarction (AMI) was a major predictor of left ventricular (LV) remodeling. We sought to clarify the effect of aging on the postinfarction inflammatory response and LV remodeling.. We studied 102 patients who underwent primary angioplasty for a first anterior Q-wave AMI. Serum CRP levels, plasma neurohormones and interleukin-6 (IL-6) levels, and LV volume by left ventriculography were serially measured. Patients were divided into two groups according to their age (>or=70 years, n=33; <70 years, n=69).. There was no difference in use of cardiovascular drugs and coronary angiographic findings. Older patients had a greater increase in LV end-diastolic volume during 2 weeks after AMI (p=0.0007) and a higher peak CRP level (12.4+/-7.3 vs. 5.5+/-4.2 mg/dl, p<0.0001), although peak CK level was comparable between the two groups. Plasma atrial natriuretic peptide, brain natriuretic peptide and IL-6 levels were higher in older patients at 2 weeks and 6 months after AMI.. Augmented and prolonged activation of the inflammatory system after AMI was observed in older patients, in association with exaggerated LV remodeling. Aging may adversely affect LV remodeling through modification of the inflammatory response after AMI.

Topics: Aged; Aging; Atrial Natriuretic Factor; C-Reactive Protein; Coronary Angiography; Creatine Kinase; Electrocardiography; Humans; Inflammation; Interleukin-6; Myocardial Infarction; Myocardial Reperfusion; Natriuretic Peptide, Brain; Prospective Studies; Regression Analysis; Ventricular Function; Ventricular Remodeling

The internal cardioverter defibrillator (ICD) is increasingly used to treat ventricular tachyarrhythmias in patients with coronary artery disease (CAD). The burden of coronary risk factors and inflammation is however not well studied in these high risk patients.. The aim of the present study was to describe the prevalence of coronary risk factors (including lipid values) and inflammation (including high sensitive-C-reactive protein, hs-CRP) in patients with CAD and ICD implants.. Baseline clinical characteristics and laboratory results of all eligible patients for the Cholesterol Lowering and Arrhythmias Recurrences after Internal Defibrillator Implantation trial (CLARIDI trial) were used. All patients had documented CAD, an ICD implant and were not yet treated with statins. Coronary risk factors, lipid values, glycated haemoglobin (HbA(1c)) and hs-CRP levels were determined.. In the 110 included patients (mean age 68+/-9 years, LVEF 40+/-17%, NYHA class II-III in 47%), a high prevalence of coronary risk factors was documented: current smoking in 18%, body mass index > or =30 kg/m(2) in 16%, blood pressure > or =140/90 mm Hg in 40%, history of diabetes in 12%, and HbA(1c) > or =6% in 16% of patients not known with diabetes. A total cholesterol >175 mg/dl was found in 76% of patients and an LDL cholesterol >100 mg/dl in 83%. Finally, median hs-CRP was 4.8 mg/l (interquartile range 2.5-13.9 mg/l). Hs-CRP values > or =2 mg/l were noted in 83% of all patients and in 68% of patients who had an ICD implant more than 6 months before inclusion.. In CAD patients with ICD implants, the burden of coronary risk factors is high, often unrecognized and/or under-treated. Persistent inflammation is found in the majority of these patients.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Belgium; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Defibrillators, Implantable; Double-Blind Method; Female; Follow-Up Studies; Glycated Hemoglobin; Greece; Heptanoic Acids; Humans; Inflammation; Inflammation Mediators; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Pyrroles; Research Design; Risk Factors; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation

The heart failure syndrome is associated with a reduced vasodilatory capacity in cutaneous microvessels. The aim of this study was to investigate the hypothesis that an altered activity of the endothelin system contributes to this reduction. The skin blood flow was recorded by laser Doppler flowmetry in patients with congestive heart failure and in age- and gender-matched controls without clinical signs of heart failure. The vessels were stimulated by iontophoretic administration of endothelin-1. The involvement of the endothelin(A) receptor was studied by co-administration of a specific antagonist; the role of the endothelin(B) receptor was studied by the administration of the selective agonist sarafotoxin 6c. The plasma levels of endothelin-1, C-reactive peptide and N-terminal-pro-Brain Natriuretic Peptide were elevated in heart failure patients. Unexpected, endothelin-1 induced an endothelin(A) mediated vasodilation. In the heart failure group the dilation was reduced to less than half as compared to control. The response to local warming was reduced in parallel indicating that the attenuation of the response in the heart failure group can be explained by the general decline in vascular reactivity. The response to endothelin(B) receptor stimulation did not differ between the groups. The reduction in endothelin-1 responsiveness is paralleled by a general reduction in microvascular vasodilatory capacity, a phenomenon of increased vascular stiffness in the of heart failure subjects.

Topics: Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Blood Pressure; Cholesterol, LDL; Endothelins; Female; Heart Failure; Humans; Inflammation; Iontophoresis; Male; Microcirculation; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Receptor, Endothelin B; Skin; Vasodilation; Vasodilator Agents; Viper Venoms

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cost-Benefit Analysis; Diabetes Complications; Female; Heart Failure; Humans; Inflammation; Kidney Diseases; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ramipril; Stroke; Ventricular Function, Left; Vitamin E

Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment.. Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed.. After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001).. Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Topics: Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Humans; Inflammation; Natriuretic Peptide, Brain

We sought to investigate the association of inflammatory biomarkers with incident heart failure (HF) events in patients at different stages of HF.. Overall, 1231 study participants undergoing diagnostic coronary and/or peripheral angiography were categorized by Universal Definition of HF (UDHF) stage A (at risk), stage B (pre-HF), and stages C or D (HF, including end-stage). Twenty-four inflammatory biomarkers were collected prior to angiography and unsupervised machine learning categorized levels of inflammation into three groups (low, medium, and high). Cox proportional hazard regression was implemented to assess the associations of inflammation level with incident HF hospitalization in each UDHF stage. Using machine learning, study participants were grouped into low (n = 443), medium (n = 570) and high inflammation categories (n = 230). Significantly higher concentrations of natriuretic peptide, troponin, and soluble ST2 were observed among those with high inflammation levels (p < 0.001). During 3.7 years of follow-up, 123 (15.1%) HF hospitalizations occurred in stage A/B and 180 (41.8%) HF hospitalizations occurred in stage C/D. In multivariable model considering low inflammation level as a reference, among patients with stage A/B, the hazard ratio (HR) (95% confidence interval [CI]) of incident HF was 2.31 (1.40-3.80) for moderate inflammation level, and 4.16 (2.35-7.37) for high inflammation level. Among patients with stage C/D, the corresponding HR (95% CI) of HF hospitalization was 1.98 (1.28-3.04) for moderate inflammation level, and 2.69 (1.69-4.28) for high inflammation level.. Patterns of inflammation severity may have differing prognostic meaning across UDHF stages.

Topics: Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Risk Factors

To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables.. In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82-2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13-1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10-1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02-1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index.. Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.

Topics: Atrial Fibrillation; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect.. High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14-1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed.. hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.

Topics: Biomarkers; Cystatin C; Growth Differentiation Factors; Heart Failure; Humans; Inflammation; Interleukin-6; Kidney; Natriuretic Peptide, Brain; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

Our aim was to assess systemic immune-inflammation index (SII) and NT-proBNP value either in singly or in combination to predict acute ST-elevation myocardial infarction (STEMI) patient prognosis.. Analyzed retrospectively the clinical features and laboratory data of STEMI confirmed patients in our hospital from January to December 2020. The levels of SII and NT-proBNP were detected. The Kaplan-Meier approach and Spearman's rank correlation coefficient were used to construct the overall major adverse cardiac event (MACE) curve. Multivariate Cox regression analysis was applied to detect MACE predictors. In addition, the Delong test and receiver operating characteristic (ROC) curve analyzed each factor performance on its own and composite multivariate index to predict MACEs.. The MACE group showed statistically significant differences in SII, NT- proBNP in comparison to the non-MACE group (. SII and NT-proBNP were independent indicators of clinical prognosis in acute STEMI patients, and they correlated positively. These factors could be combined to improve clinical prognosis.

Topics: Biomarkers; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; ST Elevation Myocardial Infarction

Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH. In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH. This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21).. NCT04753307.

Topics: Biomarkers; Heart Diseases; Humans; Inflammation; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Observational Studies as Topic; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Risk Assessment

Heart failure (HF) is a complex syndrome characterized by impaired cardiac function. Two common subtypes of HF include heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In this study, we aimed to evaluate and compare the plasma levels of 3-nitrotyrosine (3-NT)-as a marker of nitrosative/oxidative stress and myeloperoxidase (MPO)-as an indicator of inflammation between HFpEF and HFrEF. Twenty-seven patients diagnosed with HFpEF and twenty-two with HFrEF were enrolled in this study. Additionally, forty-one patients were recruited for the control group. An echocardiographic assessment was conducted, followed by the collection of blood samples from all participants. Subsequently, the levels of 3-NT and MPO were quantified using the ELISA method. Comprehensive clinical characteristics and medical histories were obtained. Circulating levels of 3-NT were significantly higher in the HFpEF patients than in the control and the HFrEF groups. Nitrosative/oxidative stress is significantly intensified in HFpEF but not in HFrEF.

Topics: Biomarkers; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Nitrosative Stress; Stroke Volume

Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD).. Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71-92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis.. In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38-2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24-3.05) and DC (OR = 0.92, 95%CI 0.86-0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84-7.95) retained a significant association.. In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Frailty; Humans; Inflammation; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulse Wave Analysis; Risk Factors; Tissue Plasminogen Activator; Troponin T; Vascular Diseases; von Willebrand Factor

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), malnutrition can be associated with intestinal congestion and systemic inflammation. These relationships have not been fully investigated in HF with mildly reduced EF (HFmrEF) and with preserved EF (HFpEF). We analyzed 420 patients with HF who underwent right heart catheterization. The relationships between hemodynamic parameters, C-reactive protein, and the controlling nutritional (CONUT) score were investigated in HFrEF, HFmrEF and HFpEF. The CONUT score of all patients was 2 [1, 4] (median [interquartile range]), and was not significantly different between the left ventricular EF (LVEF) categories (2 [1, 3] for HFrEF, 2 [1, 3] for HFmrEF, and 3 [1, 4] for HFpEF, p = 0.279). In multivariate linear regression analyses, there was a significant association between CRP and the CONUT score in HFmrEF and HFpEF, while brain natriuretic peptide and right atrial pressure were significantly associated with the CONUT score in HFrEF. Higher CONUT scores predicted a higher incidence of the composite endpoint of death or HF hospitalization within 12 months without an interaction with LVEF (p = 0.980). The CONUT score was an independent predictor of the composite endpoint, death, and HF hospitalization after adjustment for confounders in the multivariate analysis. In conclusion, inflammation was associated with malnutrition in HFmrEF and HFpEF, while congestion was an independent predictor of malnutrition in HFrEF. Malnutrition predicted worse outcomes regardless of LVEF.

Topics: C-Reactive Protein; Heart Failure; Humans; Inflammation; Malnutrition; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Function, Left

Diastolic dysfunction (DD) is more prevalent in patients with rheumatoid arthritis (RA) compared to the general population. However, its evolution over time and its significant clinical predictors remain uncharacterized. We report on baseline and prospective changes in diastolic function and its associated RA and cardiovascular (CV) predictors.. In this study, 158 RA patients without clinical CV disease (CVD) were enrolled and followed up at 4 to 6 years, undergoing baseline and follow-up echocardiography to assess for DD, as well as extensive characterization of RA disease activity and CV risk factors. Novel measures of myocardial inflammation and perfusion were obtained at baseline only. Using baseline and follow-up composite DD (E/e', Left Atrial Volume Index (LAVI) or peak tricuspid regurgitation (TR) velocity; ≥ 1 in top 25%) as the outcome, multivariable regression models were constructed to identify predictors of DD.. DD was prevalent in RA patients without clinical heart failure (HF) (40.7% at baseline) and significantly progressed on follow-up (to 57.9%). Baseline composite DD was associated with baseline RA disease activity (Clinical Disease Activity Index; CDAI) (OR 1.39; 95% CI 1.02-1.90; p=0.034). Several individual diastolic parameters (baseline E/e' and LAVI) were associated with troponin-I and brain natriuretic peptide (BNP). Baseline and follow-up composite DD, however, were not associated with myocardial inflammation, myocardial microvascular dysfunction, or subclinical atherosclerosis.. DD is prevalent in RA patients without clinical HF and increases to >50% over time. Higher RA disease activity at baseline predicted baseline composite DD. Future longitudinal studies should explore whether adverse changes in diastolic function lead to clinical HF and are attenuated by disease-modifying antirheumatic drugs (DMARDs).

Topics: Arthritis, Rheumatoid; Cardiovascular Diseases; Diastole; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.. A case-cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37-1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35-1.88)], interleukin-6 [IL-6; 1.29 (1.13-1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10-1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10-1.33)], urokinase receptor [uPAR; 1.38 (1.16-1.64)], trefoil factor 3 [TFF3; 1.27 (1.10-1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01-1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04-1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07-1.39)].. In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.. NCT00412984 and NCT00262600.

Topics: Anticoagulants; Atrial Fibrillation; Biomarkers; Growth Differentiation Factor 15; Humans; Inflammation; Interleukin-6; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Receptors, Tumor Necrosis Factor, Type I; Risk Assessment; Risk Factors; Stroke; Troponin T

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Topics: Aged; Anaerobic Threshold; Angiopoietin-Like Protein 2; Angiopoietin-like Proteins; Biomarkers; Blood Proteins; Body Composition; C-Reactive Protein; Cardiac Rehabilitation; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Echocardiography; Exercise Tolerance; Female; Hand Strength; Heart Failure; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Alopecia areata (AA) is a recurrent, immune-mediated, hair-loss disorder. It is associated with other autoimmune disorders that carry a high risk of cardiovascular disease (CVD). However, there is a lack of reports on the association of cardiovascular comorbidities and AA. Cardiac troponin I is a biomarker of myocardial ischaemia and inflammation, while N-terminal pro-B-type natriuretic peptide is used in the diagnosis of congestive heart failure. This study was conducted to assess the serum level of both markers by ELISA in 44 patients with AA compared with 44 healthy controls (HCs). None of the participants had CVD, CVD risk factors or other diseases associated with elevation of either marker. The study revealed that serum levels of both markers were significantly higher in patients with AA compared with HCs (P < 0.001). The inflammatory milieu encountered in AA may be associated with subtle myocardial inflammation that causes elevation of levels of both of these cardiac markers.

Topics: Adolescent; Adult; Alopecia Areata; Biomarkers; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values; Troponin I; Young Adult

On March 11, 2020 the World Health Organization (WHO) declared the state of global pandemic caused by the new SARS-CoV-2 (COVID-19). To date, no antivirals directed against SARS-CoV-2 or effective vaccines to combat the viral infection are available. Severe acute respiratory syndrome caused by SARS-CoV-2 is treated empirically with antivirals, anti-inflammatory, anticoagulants. The approval of an effective vaccine still takes time. In this state, it may be useful to find new therapeutic solutions from drugs already on the market. Recent hypotheses suggest that the use of AT-1 receptor antagonists (ARB) in combination with neprilisin inhibitors (NEPi) could indirectly provide clinical benefits to patients with SARS-CoV-2 and cardiac involvement. In this article we investigate and describe a possible innovative pharmacological approach for the treatment of the most severe stages of COVID-19 infection.

Topics: Aminobutyrates; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Biphenyl Compounds; COVID-19 Drug Treatment; Cytokine Release Syndrome; Cytokines; Drug Combinations; Heart Failure; Homeostasis; Humans; Inflammation; Models, Theoretical; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Receptor, Angiotensin, Type 2; Tetrazoles; Valsartan; World Health Organization

Topics: Biomarkers; C-Reactive Protein; Correlation of Data; COVID-19; Female; Ferritins; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Procalcitonin; SARS-CoV-2; Troponin T; Viremia

Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury.. A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured.. Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD.. Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Arthritis, Rheumatoid; Asymptomatic Diseases; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Female; Heart Disease Risk Factors; Heart Diseases; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptors, Tumor Necrosis Factor, Type II; Risk Assessment; Triglycerides; Troponin T

Lay abstract Inflammation describes the body’s natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation – for example, due to illnesses such as diabetes or obesity – may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as ‘natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60–79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.

Topics: Aged; Biomarkers; C-Reactive Protein; Heart Failure; Humans; Incidental Findings; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Assessment; Risk Factors; United Kingdom

Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined.. Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386).. Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.

Topics: Animals; Biomarkers; C-Reactive Protein; Cardiomyopathy, Dilated; Dog Diseases; Dogs; Female; Heart Failure; Heart Valve Diseases; Inflammation; Leukocyte Count; Male; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prospective Studies; Tumor Necrosis Factor-alpha

Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) activate inflammasome cascade in non-cancerous PNT2 cells. It is known that the endogenous biomolecules and Natriuretic Peptides (NPs), such as ANP and BNP, inhibit inflammasome activation in immune cells. Here we investigated whether ANP and BNP modify PCa inflammatory phenotype in vitro. By using PNT2, LNCaP, and PC3 cell lines, which model different PCa progression stages, we analyzed inflammasome activation and the related pathways by Western blot and IL-1β secretion by ELISA. We found that tumor progression is characterized by constitutive inflammasome activation, increased IL-1β secretion, and reduced endogenous NPs expression. The administration of exogenous ANP and BNP, via p38-MAPK or ERK1/2-MAPK, by inducing NLRP3 phosphorylation, counteract inflammasome activation and IL-1β maturation in PC3 and PC3-EVs-treated PNT2 cells, respectively. Our results demonstrate that NPs, by interfering with cell-specific signaling pathways, exert pleiotropic anti-inflammatory effects converging toward inflammasome phosphorylation and suggest that NPs can be included in a drug repurposing process for PCa.

Topics: Antineoplastic Agents; Atrial Natriuretic Factor; Cell Line, Tumor; Humans; Inflammation; Male; MAP Kinase Signaling System; Natriuretic Peptide, Brain; Neoplasm Proteins; Prostatic Neoplasms

cardiovascular disease (CVD) and chronic inflammation are implicated in the development of frailty. Longitudinal analyses of inflammatory markers, biomarkers of cardiac dysfunction and incidence of frailty are limited.. in the British Regional Heart Study, 1,225 robust or pre-frail men aged 71-92 years underwent a baseline examination, with questionnaire-based frailty assessment after 3 years. Frailty definitions were based on the Fried phenotype. Associations between incident frailty and biomarkers of cardiac dysfunction (high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) were examined, by tertile, with the lowest as reference.. follow-up data were available for 981 men. Ninety one became frail. Adjusted for age, pre-frailty, prevalent and incident CVD, comorbidity, polypharmacy and socioeconomic status, IL-6 (third tertile OR 2.36, 95% CI 1.07-5.17) and hs-cTnT (third tertile OR 2.24, 95% CI 1.03-4.90) were associated with increased odds of frailty. CRP (third tertile OR 1.83, 95% CI 0.97-4.08) and NT-proBNP (second tertile OR 0.48, 95% CI 0.23-1.01) showed no significant association with incident frailty. The top tertiles of CRP, IL-6, hscTnT and NT-proBNP were strongly associated with mortality prior to follow-up.. IL-6 is associated with incident frailty, supporting the prevailing argument that inflammation is involved in the pathogenesis of frailty. Cardiomyocyte injury may be associated with frailty risk. Associations between elevated CRP and frailty cannot be fully discounted; NT-proBNP may have a non-linear relationship with incident frailty. CRP, IL-6, hs-cTnT and NT-proBNP are vulnerable to survivorship bias.

Topics: Biomarkers; Frailty; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Troponin T

Reduced nitric oxide (NO) and a decrease in cGMP signaling mediated by soluble guanylate cyclase (sGC) has been linked to the development of several cardiorenal diseases. Stimulation of sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its effects on hemodynamics, biomarkers of inflammation, fibrosis, tissue function, and organ damage. Praliciguat treatment reduced blood pressure, improved cardiorenal damage, and attenuated the increase in circulating markers of inflammation and fibrosis. Notably, praliciguat affected markers of renal damage at a dose that had minimal effect on blood pressure. In addition, liver fibrosis and circulating markers of tissue damage were attenuated in praliciguat-treated rats. Stimulation of the NO-sGC-cGMP pathway by praliciguat attenuated or normalized indicators of chronic inflammation, fibrosis, and tissue dysfunction in the Dahl salt-sensitive rat model. Stimulation of sGC by praliciguat may present an effective mechanism for treating diseases linked to NO deficiency, particularly those associated with cardiac and renal failure. Praliciguat is currently being evaluated in patients with diabetic nephropathy and heart failure with preserved ejection fraction.

Topics: Animals; Biomarkers; Blood Pressure; Chemokine CCL2; Cyclic GMP; Fibrosis; Guanylyl Cyclase C Agonists; Inflammation; Kidney; Male; Natriuretic Peptide, Brain; Nitric Oxide; Osteopontin; Peptide Fragments; Pyrazoles; Pyrimidines; Rats; Rats, Inbred Dahl; Renal Insufficiency; Signal Transduction; Soluble Guanylyl Cyclase; Tissue Inhibitor of Metalloproteinase-1

Post-traumatic stress disorder (PTSD) is related with myocardial injury and cardiac dysfunction, while the molecular mechanism has not been clear. This study investigated whether TLR4/MyD88/NF-κB-mediated inflammation involved in myocardial injury of PTSD. Adult male Wistar rats were exposed to single-prolonged stress (SPS), which was used broadly as a animal model of PTSD. Morris Water Maze (MWM) test and forced swimming test (FST) was carried out for behavioral testing. The protein expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the left ventricular of heart and TLR4/MyD88/NF-κB-mediated inflammation were examined. Our results showed that there were obvious increased in the protein expression of ANP and BNP in heart after exposure to SPS, SPS also significantly enhanced the serum level of IL-1β and TNF-α, and meanwhile, the TLR4/MyD88/NF-κB pathway were activated. These results demonstrated that the TLR4/MyD88/NF-κB pathway were involved in the myocardial injury of PTSD, which might be one of possible molecular mechanism contributed to the pathogenesis of cardiac dysfunction in PTSD.

Topics: Animals; Atrial Natriuretic Factor; Depression; Heart; Heart Ventricles; Inflammation; Interleukin-1beta; Learning; Male; Memory; Myeloid Differentiation Factor 88; Natriuretic Peptide, Brain; NF-kappa B; Rats, Wistar; Signal Transduction; Stress Disorders, Post-Traumatic; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Remodeling

Angiopoietin-like protein 7 (ANGPTL7) is involved in extracellular matrix expression and inflammatory responses. However, the prognostic utility of ANGPTL7 among patients with acute heart failure (AHF) remains unclear.. To evaluate the association between ANGPTL7 and short-term mortality due to AHF.. Patients with AHF were prospectively studied. Serum levels of ANGPTL7 were measured by an enzyme-linked immunosorbent assay. Associations between 30- and 90-day mortality and tertiles of ANGPTL7 were assessed by multivariate logistic regression models. The study comprised 142 patients. Median patient age was 68 years, and 69.7% were male. There were 20 deaths within 30 days and 37 deaths within 90 days. Crude rates of 30-day mortality in low, intermediate, and high tertiles of ANGPTL7 were 4.6, 14.6, and 22.9%, respectively. Crude rates of 90-day mortality of corresponding tertiles were 15.2, 25.0, and 37.5%. After adjusting for potential confounders, including NT-proBNP, the high tertile of ANGPTL7 was associated with a significantly increased risk of both 30-day mortality (odds ratio [OR]: 6.77, 95% confidence interval [CI]: 1.41-32.61, p = 0.017) and 90-day mortality (OR: 3.78, 95% CI: 1.38-10.36, p = 0.010) compared with the low tertile of ANGPTL7. Although mortality risk tended to be higher in the intermediate tertile than the low tertile, it did not reach statistical significance (OR: 3.75, 95% CI: 0.73-19.14, p = 0.113 for 30-day mortality; OR: 1.88, 95% CI: 0.66-5.34, p = 0.236 for 90-day mortality).. Serum level of ANGPTL7 was independently associated with short-term mortality among patients with AHF.

Topics: Acute Disease; Aged; Angiopoietin-Like Protein 7; Angiopoietin-like Proteins; Extracellular Matrix; Female; Heart Failure; Humans; Inflammation; Logistic Models; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment

Malnutrition is a factor that defines vital prognosis in chronic heart failure.. This study investigated nutritional and metabolic disorders in patients with heart failure by examining the association of severity of heart failure with inflammatory cytokines, appetite-regulating hormones, and energy metabolism.. Subjects were 50 patients with heart failure. On admission, nutritional status was assessed, and biochemical blood tests were performed, including for serum tumor necrosis factor-α, interleukin-6, ghrelin, and leptin levels. Resting energy expenditure (REE) was also measured by indirect calorimetry to examine its association with severity of heart failure and levels of inflammatory cytokines and appetite-regulating hormones.. There were significant associations between serum brain natriuretic peptide (BNP) level and nutrition indices, indicating that nutritional status was worse when heart failure was more severe. Inflammatory cytokine levels showed significant positive correlations with BNP level. Measured REE/bodyweight was not associated with severity of heart failure, but was negatively correlated with body fat percentage and leptin levels.. Energy metabolism was not associated with serum BNP level among patients with heart failure with New York Heart Association functional class up to III. Body fat percentage and leptin levels may be a good predictor of energy metabolism in patients with heart failure.

Topics: Aged; Aged, 80 and over; Body Composition; Body Mass Index; Cytokines; Energy Metabolism; Female; Heart Failure; Hospitalization; Humans; Inflammation; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Prognosis

Evidence links markers of systemic inflammation and heart failure (HF) with ventricular arrhythmias (VA) and/or death. Biomarker levels, and the risk they indicate, may vary over time. We evaluated the utility of serial laboratory measurements of inflammatory biomarkers and HF, using time-dependent analysis.. We prospectively enrolled ambulatory patients with left ventricular ejection fraction (LVEF) ≤35% and a primary-prevention implanted cardioverter-defibrillator (ICD). Levels of established inflammatory biomarkers [C-reactive protein, erythrocyte sedimentation rate (ESR), suppression of tumourigenicity 2 (ST2), tumour necrosis factor alpha (TNF-α)] and brain natriuretic peptide (BNP) were assessed at 3-month intervals for 1 year. We assessed relationships between biomarkers modelled as time-dependent variables, VA, and death. Among 196 patients (66±14 years, LVEF 23±8%), 33 experienced VA, and 18 died. Using only baseline values, BNP predicted VA, and both BNP and ST2 predicted death. Using serial measurements at 3-month intervals, time-varying BNP independently predicted VA, and time-varying ST2 independently predicted death. C-statistic analysis revealed no significant benefit to repeated testing compared with baseline-only measurement. C-reactive protein, ESR, and TNF-α, either at baseline or over time, did not predict either endpoint.. In stable ambulatory patients with systolic cardiomyopathy and an ICD, BNP predicts ventricular tachyarrhythmia, and ST2 predicts death. Repeated laboratory measurements over a year's time do not improve risk stratification beyond baseline measurement alone.. Clinicaltrials.gov NCT01892462 (https://clinicaltrials.gov/ct2/show/NCT01892462).

Topics: Biomarkers; Cardiomyopathies; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Function, Left

Currently, the pathogenesis of congestive heart failure (CHF) in cats is not fully understood.. To identify novel biomarkers for CHF in cats caused by primary cardiomyopathy, particularly related to cardiovascular-renal axis disorder and systemic inflammatory response.. Twenty-five cats in CHF caused by primary cardiomyopathy, 12 cats with preclinical cardiomyopathy, and 20 healthy controls.. Case control and observational case series. The following serum biomarkers were compared among the 3 cat groups: a cardiorenal profile that included N-terminal pro-brain natriuretic peptide (NT-proBNP), symmetric dimethylarginine (SDMA), and creatinine and an inflammatory profile that included 7 acute-phase proteins (APPs). Survival analyses and longitudinal studies were performed in CHF cats.. All cardiorenal biomarkers were positively correlated and higher in CHF cats, and high NT-proBNP and SDMA were associated with poor clinical outcome. Cats with CHF had significantly higher leucine-rich alpha-2-glycoprotein 1, serum amyloid A, and ceruloplasmin, and these APPs were positively correlated with NT-proBNP and left atrial size. In a multivariable survival analysis, alpha-1-acid glycoprotein concentration (P = .01), body weight (P = .02) and left atrial-to-aortic root ratio (P = .01) were independent prognostic factors for CHF in these cats.. In cats, CHF is an inflammatory disorder and outcome in CHF may be determined by the extent of inflammation and possibly the amount of residual renal function. These novel biomarkers have potential use for the clinical management, prognosis, and future research into CHF and cardiomyopathy in cats.

Topics: Acute-Phase Proteins; Animals; Arginine; Biomarkers; Cardiomyopathies; Case-Control Studies; Cat Diseases; Cats; Creatinine; Female; Heart Failure; Inflammation; Kidney Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments

Aim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСН stage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000 pg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.

Topics: Biomarkers; Chronic Disease; Clostridioides difficile; Gastrointestinal Microbiome; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments

This study aimed to determine the importance of biomarkers of chronic heart failure (CHF) for assessing disease severity in euvolemic stable patients.. N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, galectin-3, cystatin-C, soluble suppression of tumorigenicity 2 (sST2), tissue type inhibitor of matrix metalloproteinase (TIMP)-1, and ceruloplasmin levels were measured in euvolemic patients with stable CHF. Severity of CHF was defined by echocardiographic and biochemical parameters.. Besides NT-proBNP, GDF-15 and cystatin C are promising biomarkers for establishing the severity of disease in euvolemic patients with stable CHF.

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling

BACKGROUND Chinese hawthorn (Crataegus pinnatifida) fruit is a traditional Chinese medicine for treatment of digestive system and cardiovascular diseases. The fruit contains polyphenol compounds, such as epicatechin, that have anti-inflammatory activity. This study aimed to investigate the effects of an alcohol extract of hawthorn fruit (HAE) on inflammation and oxidative stress in rats with doxorubicin-induced chronic heart failure (CHF). MATERIAL AND METHODS Rats were intraperitoneally injected with doxorubicin to induce CHF and subsequently treated with HAE intragastrically once daily for 6 weeks. At the end of the experiment, echocardiographic and hemodynamic parameters were assessed, and enzyme-linked immunoassays were used to detect the levels of cardiac injury markers (brain natriuretic peptide, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, copeptin, and adrenomedullin), oxidative stress markers (glutathione peroxidase and malondialdehyde), and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-1ß, and tumor necrosis factor-a). The IL-1ß, IL-6, glutathione peroxidase-1, and catalase mRNA levels were also measured by quantitative real-time polymerase chain reaction. RESULTS Our findings indicated that HAE exerts a cardioprotective effect, as shown by improved echocardiographic and hemodynamic parameters, decreased activity of serum myocardial enzymes, reduced serum levels of CHF markers, and inhibited inflammatory response in cardiac tissue. In addition, HAE treatment downregulated the mRNA expression of IL-1ß and tumor necrosis factor-alpha and upregulated the mRNA expression of glutathione peroxidase-1 and catalase compared with untreated doxorubicin-induced CHF rats. CONCLUSIONS HAE shows promise for the prevention and treatment of CHF. The cardioprotective effect of HAE appears to be related to inhibition of both the inflammatory response and oxidative stress in vivo.

Topics: Adrenomedullin; Animals; Antioxidants; Aspartate Aminotransferases; Chromatography, High Pressure Liquid; Chronic Disease; Crataegus; Creatine Kinase; Cytokines; Doxorubicin; Electrocardiography; Ethanol; Fruit; Glutathione Peroxidase; Glycopeptides; Heart Failure; Heart Function Tests; Inflammation; L-Lactate Dehydrogenase; Male; Malondialdehyde; Natriuretic Peptide, Brain; Oxidative Stress; Plant Extracts; Polyphenols; Rats, Wistar; RNA, Messenger

Topics: Animals; Atrial Natriuretic Factor; Bacterial Proteins; Bacterial Toxins; Caco-2 Cells; Cardiovascular Diseases; Cell Line, Tumor; Cells, Cultured; Clostridioides difficile; Clostridium Infections; Cytokines; Disease Models, Animal; Enterotoxins; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intestines; Natriuretic Peptide, Brain; Neutrophils; Serum Albumin, Human; Vascular Endothelial Growth Factor A; Zebrafish

This study aimed to determine the relationship between fetal exposure to intra-amniotic infection/inflammation (IAI) and fetal heart ventricular function as assessed by circulatory levels of N-terminal fragment brain natriuretic protein (NT-proBNP) and the Tei index.. We analyzed 70 samples of paired amniotic fluid (AF) and cord blood retrieved from mothers who delivered preterm at <34 weeks as follows: Yes-IAI (. IAI was characterized by significantly higher levels of AF (. Fetal myocardial left ventricular function does not seem to be significantly impaired in fetuses born alive due to IAI if delivery of the fetus occurs immediately following the diagnosis of IAI.

Topics: Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Chorioamnionitis; Echocardiography, Doppler; Female; Fetal Blood; Fetal Heart; Humans; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-6; Male; Mass Spectrometry; Natriuretic Peptide, Brain; Peptide Fragments; Placenta; Pregnancy; Premature Birth; Ventricular Function, Left

Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1β) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy.. hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded.. 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDL-cholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl.. One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.

Topics: Aged; Anti-Inflammatory Agents; Anticholesteremic Agents; Atherosclerosis; C-Reactive Protein; Cholesterol, LDL; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Ezetimibe; Female; Humans; Incidence; Inflammation; Male; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies

Cardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF-21) and monocyte chemoattractant protein 1 (MCP-1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF-21 and MCP-1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia.. Plasma FGF-21 and MCP-1 were measured in a cross-sectional study among the three study groups: 19 patients with HFrEF with cardiac cachexia, 19 patients with HFrEF without cachexia, and 19 patients with ischaemic heart disease and preserved ejection fraction. Patients with HFrEF and cardiac cachexia displayed higher FGF-21 levels median (inter quantile range) 381 (232-577) pg/mL than patients with HFrEF without cachexia 224 (179-309) pg/mL and ischaemic heart disease patients 221 (156-308) pg/mL (P = 0.0496). No difference in MCP-1 levels were found among the groups (P = 0.345). In a multivariable regression analysis, FGF-21 (logarithm 2) was independently associated with interleukin 6 (logarithm 2) (P = 0.015) and lower muscle mass (P = 0.043), while no relation with N-terminal pro-hormone brain natriuretic peptide was observed.. Fibroblast growth factor 21 (FGF-21) levels were elevated in patients with HFrEF and cardiac cachexia, which could be mediated by increased inflammation and muscle wasting rather than impaired cardiac function.

Topics: Aged; Aged, 80 and over; Biomarkers; Cachexia; Cardiovascular Diseases; Case-Control Studies; Chemokine CCL2; Chronic Disease; Cross-Sectional Studies; Denmark; Female; Fibroblast Growth Factors; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Muscular Atrophy; Myocardial Ischemia; Natriuretic Peptide, Brain; Stroke Volume; Wasting Syndrome

Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort.. We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007).. Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets).

Topics: Aged; Anemia, Iron-Deficiency; Aryldialkylphosphatase; Biomarkers; Body Fluids; Eating; Female; Heart Failure; Humans; Inflammation; Iron Deficiencies; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Proteins; Renal Insufficiency, Chronic; Stroke Volume; Tartrate-Resistant Acid Phosphatase; Transferrin

Recently, there has been an increasing interest in the potential clinical use of several inflammatory indexes, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-immune-inflammation index (SII). This study aimed at assessing whether these markers could be early indicators of pulmonary hypertension (PH) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 185 patients were enrolled in our retrospective study from January 2017 to January 2019. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the clinical significance of these biomarkers to predict PH in patients with AECOPD. According to the diagnostic criterion for PH by Doppler echocardiography, the patients were stratified into two groups. The study group consisted of 101 patients complicated with PH, and the control group had 84 patients. The NLR, PLR, and SII values of the PH group were significantly higher than those of the AECOPD one (

Topics: Aged; Biomarkers; Blood Platelets; Carboxypeptidase B; Disease Progression; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Inflammation; Lymphocytes; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Neutrophils; Peptide Fragments; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; ROC Curve

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

Pitavastatin inhibits 3 hydroxy 3 methyl glutaryl coenzyme A (HMGCoA) reductase enzyme, preventing cholesterol synthesis along with elevating high density apolipoprotein A1 (Apo-A1). The present study was designed to evaluate cardioprotective potential of pitavastatin at 1 mg/kg/day and 3 mg/kg/day dose for 14 days in low dose isoproterenol (ISO) (5 mg/kg/day for 7 consecutive days) induced myocardial damage. ISO administration induced significant reduction in endogenous antioxidant enzymes like reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and raised thiobarbituric acid reactive substances (TBARS) indicating activated lipid peroxidation. Along with this, a significant increase in level of cardiac injury biomarkers vie, creatine kinase (CK-MB), lactate dehydrogenase (LDH), aspartate amino transferase (AST), tumor necrosis factor (TNF-α) and transforming growth factor (TGF-β) as well as brain natriuretic peptide (BNP). Histological examination also revealed marked myocardial tissue damage in ISO treated rats. However, pretreatment with pitavastatin (3 mg/kg/day) significantly maintained nearly normal levels of cardiac biomarkers and oxidant antioxidant status as well as lipid peroxidation in ISO induced MI rats. Cardiac histological assessment and infarct size assessment also showed marked reduction in myocardial architecture alteration including infarct size as well as collagen deposition by pitavastatin that strongly supported biochemical findings. These observations strongly corroborate that pitavastatin prevents myocardial damages via up regulation of endogenous oxidants along with its hypocholesterolemic activity.

Topics: Animals; Antioxidants; Aspartate Aminotransferases; Catalase; Collagen; Creatine Kinase, MB Form; Free Radicals; Glutathione; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Quinolines; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.. Infants born at 22-27 weeks' gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.. High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.. High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

Topics: Biomarkers; Chemokine CCL2; Ductus Arteriosus, Patent; Echocardiography; Growth Differentiation Factor 15; Humans; Ibuprofen; Infant, Extremely Premature; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Inflammation; Interleukin-10; Interleukin-12 Subunit p35; Interleukin-6; Interleukin-8; Natriuretic Peptide, Brain; Platelet-Derived Growth Factor; Prospective Studies; Risk; Sweden

Influence of pre-existing treatment with aspirin and/or statins prior to a first acute coronary syndrome (ACS) on clinical presentation, infarct size and inflammation markers. We analyzed patients from the Swiss Program University Medicine ACS-cohort (SPUM-ACS; ClinicalTrials.govnumber:NCT01075867).. 1639 patients were categorized into 4 groups: (1) patients without either drug (n = 1181); (2) patients only on aspirin (n = 157); (3) patients only on statins (n = 133) and (4) patients on both drugs (n = 168). Clinical features, electrocardiogram (ECG), creatinine kinase (CK, U/l), high-sensitivity troponin T (hsTNT, μg/l), N-terminal brain natriuretic peptide (NT-proBNP, ng/l), leucocytes (Lc, G/l), neutrophils (Nc, G/l), C-reactive protein (CRP, mg/l) and angiographic features were documented at baseline.. Incidences of ST-elevation myocardial infarction (STEMI) were 64% in group 1, 45% in group 2, 52% in group 3 and 40% in group 4 (p < 0.0001). Those with both drugs had significantly lower CK (median 145 U/l, interquartile range (IQR) 89-297), hsTNT (median 0.13 μg/l, IQR 0.03-0.52) and higher left ventricular ejection fraction values (LVEF) (mean 55 ± 12%) compared to untreated patients (median CK 273 U/l, IQR 128-638; median hsTNT 0.26 μg/l, IQR 0.08-0.85; mean LVEF 51 ± 11%) (p < 0.0001, p = 0.001, p = 0.028, respectively). Co-medicated groups matched for high risk factors presented less frequently as STEMIs (p < 0.0001), had significantly smaller infarcts determined by CK and hsTNT (both p < 0.0001) and lower CRP levels (p = 0.01) compared to patients without pre-existing treatment with either drug.. Pre-existing treatment with aspirin and/or statins and particularly with their combination changes the clinical presentation, infarct size, inflammation markers and LVEF in patients suffering their first ACS.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Biomarkers; C-Reactive Protein; Coronary Angiography; Electrocardiography; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Stroke Volume; Troponin T; Ventricular Function, Left

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

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti-inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg

Topics: Animals; Asymptomatic Diseases; Atorvastatin; Dog Diseases; Dogs; Echocardiography; Female; Hemodynamics; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Mitral Valve Prolapse; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Tumor Necrosis Factor-alpha

Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors.. We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position.. Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (-0.63 kg, 95% CI, -0.99 to -0.28); the equivalent association for cystatin C was -0.60 kg (95% CI, -0.94 to -0.25) and for IL-6 was -0.76 kg (95% CI, -1.11 to -0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment.. Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.

Topics: Aged; Biomarkers; Blood Pressure; Body Height; Body Mass Index; Cholesterol; Cystatin C; E-Selectin; Follow-Up Studies; Glycated Hemoglobin; Heart Diseases; Humans; Inflammation; Interleukin-6; Kidney Diseases; Lipoproteins, HDL; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Physical Fitness; Risk Factors; Smoking; Socioeconomic Factors; United Kingdom

Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF.. The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events.. Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations.. Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Cytokines; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Inflammation; Interleukin-11; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Prognosis; Proportional Hazards Models; Prospective Studies; ROC Curve; Ventricular Function, Left

Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent cardiovascular damage. However, the interrelationship among dendritic cells, target organs inflammation/fibrosis induced by mineralocorticoid receptor, and NGAL-dependence remains unknown.. We studied the role of dendritic cells in mineralocorticoid receptor-dependent tissue remodeling and whether NGAL can modulate the inflammatory response of dendritic cells after mineralocorticoid receptor activation.. Cardiovascular and renal remodeling induced by Aldo and high-salt diet [nephrectomy-Aldo-salt (NAS) model] were analyzed in CD11c.DOG mice, a model which allows dendritic cells ablation by using diphtheria toxin. In addition, in-vitro studies in NGAL-knock out dendritic cells were performed to determine the immunomodulatory role of NGAL upon Aldo treatment.. The ablation of dendritic cells prevented the development of cardiac hypertrophy, perivascular fibrosis, and the overexpression of NGAL, brain natriuretic peptide, and two profibrotic factors induced by NAS: collagen 1A1 and connective tissue growth factor. We determined that dendritic cells were not required to prevent renal hypertrophy/fibrosis induced by NAS. Between different immune cells analyzed, we observed that NGAL abundance was higher in antigen-presenting cells, while in-vitro studies showed that mineralocorticoid receptor stimulation in dendritic cells favored NGAL and IL-23 expression (p19 and p40 subunits), which are involved in the development of fibrosis and the Th17-driven response, respectively.. NGAL produced by dendritic cells may play a pivotal role in the activation of adaptive immunity that leads to cardiovascular fibrosis during mineralocorticoids excess.

Topics: Aldosterone; Animals; Cardiomegaly; Cardiovascular System; CD11 Antigens; Coculture Techniques; Dendritic Cells; Female; Fibrosis; Hyperaldosteronism; Inflammation; Interleukin-23 Subunit p19; Kidney; Lipocalin-2; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Natriuretic Peptide, Brain; Receptors, Mineralocorticoid; Sodium Chloride, Dietary; T-Lymphocytes

Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).. Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.. In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.. Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

Topics: Aged; Agouti-Related Protein; Biomarkers; Coronary Artery Disease; Coronary Vessels; Female; Humans; I-kappa B Kinase; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Urokinase Plasminogen Activator; Renin

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Immunoglobulins, Intravenous; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lacticaseibacillus casei; Male; Mice; Mice, Inbred C57BL; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Receptors, Interleukin-1; Vasculitis

C-reactive protein (CRP) increases after strenuous exercise. It has been a concern that prolonged strenuous exercise may be harmful and induce a deleterious inflammatory response. The purpose of this study was to (a) assess and quantify the magnitude of CRP response following an endurance cycling competition in healthy middle-aged recreational cyclists. (b) Identify important determinants of this response. (c) Identify the relationship between CRP, myocardial damage (cardiac Troponin I (cTnI)), and myocardial strain (B-type natriuretic peptide [BNP]). (d) Identify the relationship between CRP and clinical events, defined as utilization of healthcare services or self-reported unusual discomfort. Race time was used as a measure of physical fitness. A total of 97 individuals (43±10 years of age, 74 [76%] males) were assessed prior to and 0, 3, and 24 hours following the 91-km mountain bike race "Nordsjørittet" (Sandnes, Norway, June 2013). There was a highly significant increase in CRP from baseline to 24 hours (0.9 (0.5-1.8) mg/L vs. 11.6 (6.0-17.5) mg/L (median[IQR]), P<.001), with no correlation of CRP to cTnI and BNP at any time-point. CRP was strongly correlated to race time at baseline (r=.38, P<.001) and at 24 hours following the race (r=.43, P<.001), In multivariate models, race time was an independent predictor of CRP both at baseline and at 24 hours (P<.01). There was no relationship between CRP levels and clinical events. In conclusion, high physical fitness was associated with reduction in both basal- and exercise-induced CRP. No adverse relationship was found between high intensity physical exercise, CRP levels, and outcomes.

Topics: Adult; Bicycling; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Physical Fitness; Prospective Studies; Troponin I

To determine the impact of long distance rowing (160km, nonstop) on standard biological parameters and to study the relation between inflammation, myocardial necrosis, lipid profile, heart rate and energy expenditure.. Electrolytes, lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), procalcitonin (PCT), high-sensitive troponin T (hs-cTnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were measured on non-fasting venous blood samples collected 8h before and after the rowing race on five healthy competitors. Heart rate and energy expenditure were measured using sporting self-measurement devices.. After 16.5h of race, significant increases in median CRP (+25.2mg/l; p=0.04), IL-6 (+1.85pg/ml; p=0.04), TNF-α (+1.2pg/ml; p=0.04) and NT-proBNP levels (+88.8pg/ml; p=0.04) were observed, and a close to significant elevation for hs-cTnT(+6ng/l; p=0.06) and PCT (+0.14μg/l; p=0.07). On the other hand, significant decrease in median total cholesterol (-0.5mmol/l; p=0.04), triglycerides (-0.7mmol/l; p=0.04) were observed. Furthermore, significant correlations between the maximal heart rate reached during the race and CRP (r=0.90; p=0.03), IL-6 (r=0.90; p=0.03), and NT-proBNP (r=0.90; p=0.03) were observed, whereas no such associations were retrieved with median heart rate, the percentage of time passed over 70% of maximal heart rate or energy expenditure during the race. There was no association between PCT, NT-proBNP, hs-cTnT, inflammatory biomarkers, lipid profile or heart rate parameters.. Long distance rowing induces inflammation and myocardial strain related to the maximal effort generated during the race, but has a favourable effect on lipid profile.

Topics: Adult; Athletes; Biomarkers; C-Reactive Protein; Calcitonin; Electrolytes; Exercise; Female; Humans; Inflammation; Interleukin-6; Lipids; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Troponin T; Tumor Necrosis Factor-alpha; Water Sports

MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3‑month‑old and 12‑month‑old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups. Eight significantly upregulated miRNAs were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), followed by in silico target gene prediction. Functional annotation analysis of the predicted targets was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. As a result, significantly impaired left ventricular diastolic function was detected in the 12‑month‑old SHRs, alongside increased myocyte cross‑sectional area and percentage area of fibrosis, elevated reactive oxygen species production and reduced microvessel density (P<0.05). Compared with the 3‑month‑old SHRs, 21 miRNAs were significantly upregulated and five miRNAs were downregulated in 12‑month‑old rats (P<0.05). Eight upregulated, remodeling‑associated miRNAs, including rno‑miR‑132‑3p, rno‑miR‑182, rno‑miR‑208b‑3p, rno‑miR‑212‑3p, rno‑miR‑214‑3p, rno‑miR‑218a‑5p, rno‑miR‑221‑3p and rno‑miR‑222‑3p, underwent bioinformatics analysis. The target genes were significantly enriched in 688 GO terms and 39 KEGG pathways, including regulation of peptidyl‑tyrosine phosphorylation, regulation of protein serine/threonine kinase activity, adrenergic signaling in cardiomyocytes, ErbB signaling pathway, mTOR signaling pathway, FoxO signaling pathway, Ras signaling pathway, insulin secretion, adipocytokine signaling pathway, HIF‑1 signaling pathway, Rap1 signaling pathway, VEGF signaling pathway and TNF signaling pathway. Collectively, the present study identified a dysregulated miRNA profile in aging SHRs, which targeted numerous signaling pathways associated with cardiac hypertrophy, autophagy, insulin metabolism, angiogenesis and inflammatory response.

Topics: Aging; Animals; Cluster Analysis; Computational Biology; Down-Regulation; Electrocardiography; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Ontology; Heart Ventricles; High-Throughput Nucleotide Sequencing; Inflammation; Male; MicroRNAs; Molecular Sequence Annotation; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Rats, Inbred SHR; Reactive Oxygen Species; Reproducibility of Results; Sequence Analysis, RNA; Statistics as Topic; Up-Regulation

This study aimed to evaluate whether the combination of inflammatory markers could provide predictive powers for mortality in individual patients on dialysis and develop a predictive model for mortality according to dialysis modality. Data for inflammatory markers were obtained at the time of enrollment from 3,309 patients on dialysis from a prospective multicenter cohort. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. Cox proportional hazards regression analysis was used to derive a prediction model of mortality and the integrated area under the curve (iAUC) was calculated to compare the predictive accuracy of the models. The incremental additions of albumin, high-sensitive C-reactive protein (hsCRP), white blood count (WBC), and ferritin to the conventional risk factors showed the highest predictive powers for all-cause mortality in the entire population (NRI, 21.0; IDI, 0.045) and patients on peritoneal dialysis (NRI, 25.7; IDI, 0.061). The addition of albumin and hsCRP to the conventional risk factors markedly increased predictive powers for all-cause mortality in HD patients (NRI, 19.0; IDI, 0.035). The prediction model for all-cause mortality using conventional risk factors and combination of inflammatory markers with highest NRI value (iAUC, 0.741; 95% CI, 0.722-0.761) was the most accurate in the entire population compared with a model including conventional risk factors alone (iAUC, 0.719; 95% CI, 0.700-0.738) or model including only significant conventional risk factors and inflammatory markers (iAUC, 0.734; 95% CI, 0.714-0.754). Using multiple inflammatory markers practically available in a clinic can provide higher predictive power for all-cause mortality in patients on dialysis. The predictive model for mortality based on combinations of inflammatory markers enables a stratified risk assessment. However, the optimal combination for the predictive model was different in each dialysis modality.

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Ferritins; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Models, Theoretical; Natriuretic Peptide, Brain; Precision Medicine; Prospective Studies; Renal Dialysis; Risk Assessment; Serum Albumin, Human

Response to cardiac resynchronization therapy (CRT) can currently be assessed by clinical or echocardiographic criteria, and there is no strong evidence supporting the use of one rather than the other. Reductions in B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been shown to be associated with CRT response. This study aims to assess variation in BNP and CRP six months after CRT and to correlate this variation with criteria of functional and echocardiographic response.. Patients undergoing CRT were prospectively enrolled between 2011 and 2014. CRT response was defined by echocardiography (15% reduction in left ventricular end-systolic volume) and by cardiopulmonary exercise testing (10% increase in peak oxygen consumption) from baseline to six months after device implantation.. A total of 115 patients were enrolled (68.7% male, mean age 68.6±10.5 years). Echocardiographic response was seen in 51.4% and 59.2% were functional responders. There was no statistical correlation between the two. Functional response was associated with a significantly greater reduction in BNP (-167.6±264.1 vs. -24.9±269.4 pg/ml; p=0.044) and CRP levels (-1.6±4.4 vs. 2.4±9.9 mg/l; p=0.04). Nonetheless, a non-significant reduction in BNP and CRP was observed in echocardiographic responders (BNP -144.7±260.2 vs. -66.1±538.2 pg/ml and CRP -7.1±24.3 vs. 0.8±10.3 mg/l; p>0.05).. An increase in exercise capacity after CRT implantation is associated with improvement in myocardial remodeling and inflammatory biomarkers. This finding highlights the importance of improvement in functional capacity after CRT implantation, not commonly considered a criterion of CRT response.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiac Resynchronization Therapy; Echocardiography; Female; Heart Failure; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Remodeling

Circulating microRNAs (miRs) may act as diagnostic and prognostic biomarkers for cardiovascular events in coronary artery bypass graft (CABG) surgery patients. This study measured changes in cardiac- and muscle-related miRs and cardiac and inflammatory biomarkers in acute coronary syndrome patients undergoing CABG surgery as well as investigated the correlations between these indicators.. Creatine kinase-MB (CK-MB), brain natriuretic peptide (BNP), cardiac troponin T (cTnT), interleukin-6 (IL-6), IL-8, IL-10, high-sensitivity C-reactive protein, and tumor necrosis factor-α were measured, and real-time quantitative polymerase chain reaction was performed to determine the plasma levels of miR-1, miR-133a, miR-208a, and miR-499 before and after surgery in 27 acute coronary syndrome patients. Left ventricular ejection fraction was also analyzed in a 3-month follow-up.. miR-1, miR-133a, and miR-208a increased significantly (P = 0.0011; P = 0.0057; P = 0.0197, respectively) and the CK-MB, cTnT, BNP, and IL-6 levels were augmented after surgery. miR-133a, miR-208a, and miR-499 positively correlated with cTnT (r = 0.302, P = 0.027; r = 0.326, P = 0.016; r = 0.298, P = 0.029, respectively), but only miR-208a significantly correlated with CK-MB (r = 0.278, P = 0.041). miR-133a and miR-208a were significantly related to IL-6 (r = 0.287, P = 0.036; r = 0.292, P = 0.032, respectively). However, there were no significant associations between miRs and BNP or 3-month left ventricular ejection fraction.. CABG surgery-induced myocardial reperfusion damage and subsequent inflammation were related to changes in miR-1, miR-133a, and miR-208a. Notably, miR-208a was the only indicator associated with CK-MB, cTnT, and IL-6, which may reflect heart injury and inflammation in these patients.

Topics: Aged; Coronary Artery Bypass; Creatine Kinase, MB Form; Female; Humans; Inflammation; Interleukin-6; Male; MicroRNAs; Middle Aged; Myocardial Reperfusion Injury; Natriuretic Peptide, Brain; Troponin T

BACKGROUND The aim of this study was to investigate the effects of sulforaphane (SFN), a natural isothiocyanate compound, in a rabbit ascending aortic cerclage model of chronic heart failure (CHF). MATERIAL AND METHODS Thirty New Zealand White rabbits were divided into the sham operation group (n=10), the CHF group (n=10), and the CHF + SFN group (n=10) treated with subcutaneous SFN (0.5 mg/kg) for five days per week for 12 weeks. After 12 weeks, echocardiography and biometric analysis were performed, followed by the examination of the rabbit hearts. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to detect levels of inflammatory cytokines, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS In the CHF group, compared with the sham operation group, there was an increase in the heart weight to body weight ratio (HW/BW), the left ventricular weight to body weight ratio (LVW/BW), the left ventricular end diastolic diameter (LVEDD), the left ventricular end systolic diameter (LVESD), plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels, the cardiac collagen volume fraction (CVF), apoptotic index, expression levels of collagen I, collagen III, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in the myocardial tissue, and a decrease in the left ventricular shortening fraction (LVFS) and left ventricular ejection fraction (LVEF), and cardiac superoxide dismutase (SOD) activity. These changes were corrected in the SFN-treated group. CONCLUSIONS In a rabbit model of CHF, treatment with SFN improved cardiac function and remodeling by inhibiting oxidative stress and inflammation.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Chronic Disease; Collagen; Cytokines; Female; Fibrosis; Heart Failure; Heart Function Tests; Hemodynamics; Inflammation; Isothiocyanates; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Rabbits; RNA, Messenger; Sulfoxides

To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH.. Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3-9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8-3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10-13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays.. Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments.. Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.

Topics: Aftercare; Aged; Biomarkers; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Inflammation; Interleukin-6; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Neovascularization, Pathologic; Peptide Fragments; Placenta Growth Factor; Scleroderma, Systemic; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor D; Vascular Endothelial Growth Factor Receptor-1; Vascular Resistance; Walk Test

To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures.. Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth.. Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α (TNF-α), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size.. Compared with PHEU (N = 156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status.. PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Child; Cross-Sectional Studies; Cytokines; Echocardiography; Environmental Exposure; Female; Healthy Volunteers; HIV Infections; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Serum; Severity of Illness Index; Troponin T

Current validated cardiovascular (CV) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis (RA) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population-based risk calculators.. Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C-reactive protein (CRP) level at 2 consecutive time points 1 year apart (CRP decrease group and CRP increase group, respectively) were included in this study. We estimated 10-year CV risk using the following calculators: Framingham Risk Score, 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score, Reynolds Risk Score (RRS), and QRISK2. Of these calculators, only the RRS includes a variable addressing the CRP level. Paired t-tests were performed to compare risk scores at baseline and 1-year follow-up. We calculated the correlations between the changes in risk scores and changes in pro-B-type natriuretic peptide (pro BNP), a surrogate marker of CV risk.. One hundred eighty RA patients were included in the study (mean age 57.8 years, 84% female, 80% seropositive). Of the calculators studied, only the RRS was sensitive to changes in inflammation; an increase in inflammation was associated with increased estimated CV risk (P < 0.0001), and only the RRS was correlated with changes in proBNP (r = 0.17, P = 0.03).. Our data showed no significant change in CV risk estimated using validated general population CV risk calculators except for the RRS. These findings suggest that CV risk may be modulated by changes in inflammation in RA, which is not typically considered when using existing CV risk calculators.

Topics: Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Assessment; Risk Factors; Time Factors

Essentials Inflammatory and cardiac diseases are associated with increased venous thromboembolism (VTE) risk. Our prospective study assessed rise in inflammatory or cardiac biomarkers and VTE risk. A greater 6-year rise in N-terminal natriuretic peptide is associated with increased VTE incidence. Volume overload or impending cardiac disease may contribute to VTE occurrence.. Background We previously showed that participants in the population-based Atherosclerosis Risk in Communities (ARIC) cohort with elevated levels of blood biomarkers of inflammation or cardiac disease were at increased risk of venous thromboembolism (VTE). Objective We hypothesized that ARIC participants with larger 6-year increases in the levels of three biomarkers - C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin T - would also have an increased subsequent risk of VTE. Methods We measured changes in the levels of these biomarkers in 9844 participants from 1990-1992 to 1996-1998, and then identified VTEs through 2015. Results A greater 6-year rise in the level of NT-proBNP, but not in that of CRP or troponin T, was significantly associated with increased VTE incidence over a median of 17.6 years of follow-up. After adjustment for other VTE risk factors, those whose NT-proBNP level rose from < 100 pg mL

Topics: Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Incidence; Inflammation; Inflammation Mediators; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Troponin T; United States; Up-Regulation; Venous Thromboembolism

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and radiofrequency catheter ablation of AF (RCAAF) has become increasingly popular. Cardiac stress and inflammation have been associated with AF. This study was performed to determine whether the pre- or post-AF ablation levels of high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are predictive of AF recurrence.. This multicenter prospective cohort study involved patients undergoing RCAAF in Switzerland and Canada. The primary endpoint was the recurrence of AF or atrial flutter at 6 months.. Of 202 patients, 195 completed follow-up (age, 57.5 ± 9 years; mean left ventricular ejection fraction, 62%; mean left atrial size, 19.4 cm. The pre-ablation hs-CRP level and immediate post-ablation NT-proBNP level were markers for atrial arrhythmia recurrence after RCAAF. This confirms growing evidence of the role of inflammation in the pathogenesis of AF. These biomarkers appear to be promising stratification tools for selection and management of patients undergoing RCAAF.

Topics: Atrial Fibrillation; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Prognosis; Prospective Studies; Radiofrequency Ablation; Recurrence; Risk Factors; Survival Rate

This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers.. Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy.. From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide. Interactions with statin treatment were also assessed.. The two models-model 1 (endostatin, interleukin 8, soluble ST2, troponin T, galectin 3, and chemokine [C-C motif] ligand 21) and model 2 (troponin T, soluble ST2, galectin 3, pentraxin 3, and soluble tumor necrosis factor receptor 2)-significantly improved the CORONA and Seattle HF models but added only modestly to their Harrell's C statistic and net reclassification index. In addition, rosuvastatin had no effect on the levels of a wide range of inflammatory and extracellular matrix markers, but there was a tendency for patients with a lower level of biomarkers in the 2 panels to have a positive effect from statin treatment.. In the specific HF patient population studied, a multimarker approach using the particular panel of biomarkers measured was of limited clinical value for identifying future risk of adverse outcomes.

Topics: Biomarkers; Blood Proteins; C-Reactive Protein; Cardiovascular Diseases; Cause of Death; Chemokine CCL21; Chronic Disease; Endostatins; Galectin 3; Galectins; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-8; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Rosuvastatin Calcium; Serum Amyloid P-Component; Troponin T

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

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

This study sought to determine the relationship between growth differentiation factor (GDF)-15 and clinical outcomes in ambulatory patients with heart failure and reduced ejection fraction (HFrEF).. The prognostic utility of GDF-15, a member of the transforming growth factor-β cytokine family, among patients with HF is unclear.. We assessed GDF-15 levels in 910 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial, a randomized clinical trial of exercise training in patients with HFrEF. Median follow-up was 30 months. Cox proportional hazard models assessed the relationships between GDF-15 and clinical outcomes.. The median GDF-15 concentration was 1,596 pg/ml. Patients in the highest tertile of GDF-15 were older and had measurements of more severe HF (higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentrations and lower peak oxygen uptake on cardiopulmonary exercise testing [CPX]). GDF-15 therapy was a significant predictor of all-cause death (unadjusted hazard ratio [HR]: 2.03 when GDF-15 was doubled; p < 0.0001). This association persisted after adjustment for demographic and clinical and biomarkers including high sensitivity troponin T (hs-TnT) and NT-proBNP (HR: 1.30 per doubling of GDF-15; p = 0.029). GDF-15 did not improve discrimination (as measured by changes in c-statistics and the integrated discrimination improvement) in addition to baseline variables, including hs-TnT and NT-proBNP or variables found in CPX testing.. In demographically diverse, well-managed patients with HFrEF, GDF-15 therapy provided independent prognostic information in addition to established predictors of outcomes. These data support a possible role for GDF-15 in the risk stratification of patients with chronic HFrEF. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437).

Topics: Adult; Aged; Chronic Disease; Exercise Therapy; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke Volume

To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF).. Serum and saliva were collected from 75 hospitalized patients with HF (57 ± 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman's ρ and Bland-Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation.. Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum-salivary CRP, weak correlation for serum-salivary IL-6, and no correlations for serum-salivary BNP and IL-10. The Bland-Altman test showed good salivary-serum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Humans; Inflammation; Interleukin-10; Interleukin-6; Kentucky; Male; Middle Aged; Natriuretic Peptide, Brain; Saliva; Salivary Proteins and Peptides

Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation.. In an observational prospective cohort study, we enrolled consecutive adult patients admitted for noncardiac reasons to the intensive care unit (ICU) in two tertiary care centers. We measured cTnT, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cutoff ≥15 ng/L and concomitant changes on electrocardiogram, patients were categorized as "definite myocardial infarction (MI)," "possible MI," "cTnT rise only," or "no cTnT rise." Within each group, associations between CRP, IL-6, PCT, NT-proBNP, and cTnT were investigated using mixed effect models.. One hundred seventy-two patients were included in the analysis of whom 84% had a cTnT rise ≥15 ng/L. Twenty-one patients (12%) had a definite MI, 51 (30%) had a possible MI, and 73 (42%) had a cTnT rise only. At the time of peak cTnT, 71% of patients were septic and 67% were on vasopressors.Multivariable analysis showed a significant association between cTnT and IL-6 in all patients with a cTnT rise independent of age, gender, renal function, and cardiovascular risk factors. In patients without a definite MI, cTnT levels were significantly associated with PCT and NT-proBNP values. In patients without elevated cTnT levels, there was no associated NT-proBNP rise.. In ICU patients admitted for non-cardiac reasons, serial cTnT levels were independently associated with markers of systemic inflammation and NT-proBNP.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Critical Illness; Electrocardiography; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex.. Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively.. The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01-1.25) and 1.09 (1.01-1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio.. Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD.

Topics: Arteriosclerosis; C-Reactive Protein; Extracellular Fluid; Female; Humans; Inflammation; Intracellular Fluid; Longitudinal Studies; Male; Malnutrition; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulse Wave Analysis; Renal Dialysis; Risk Factors; Serum Albumin

Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N-terminal pro-brain natriuretic peptide (NT-proBNP), an indicator of haemodynamic wall stress.. Plasma GDF15 and NT-proBNP were prospectively measured in 916 consecutive patients with HFrEF (EF <50%; n = 730) and HFpEF (EF ≥50%; n = 186), and measured again at 6 months in 488 patients. Patients were followed up for a composite outcome of death or first HF rehospitalization.. Median GDF15baseline values were similarly elevated in HFpEF [2862 (1812 represent the 25th percentile and 4176 represent the 75th percentile) ng/L] and HFrEF [2517 (1555, 4030) ng/L] (P = 0.184), whereas NT-proBNP was significantly lower in HFpEF than HFrEF (1119 ng/L vs. 2335 ng/L, P < 0.001). Independent correlates of GDF15baseline were age, systolic blood pressure, New York Heart Association (NYHA) class, diabetes, atrial fibrillation, sodium, haemoglobin, creatinine, diuretic therapy, high sensitivity troponin T (hsTnT) and NT-proBNP (all P < 0.05). During a median follow-up of 23 months, there were 379 events (307 HFrEF, 72 HFpEF). GDF15 remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors including hsTnT and NT-proBNP (adjusted hazard ratio 1.76 per 1 Ln U, 95% confidence interval 1.39-2.21; P < 0.001), regardless of HF group (Pinteraction  = 0.275). GDF15baseline provided incremental prognostic value when added to clinical predictors, hsTnT and NT-proBNP (area under receiver operating characteristic curve increased from 0.720 to 0.740, P < 0.019), with a net reclassification improvement of 0.183 (P = 0.004). Patients with ≥20% GDF156months increase had higher risk for composite outcome (adjusted hazard ratio 1.68, 95% confidence interval 1.15-2.45; P = 0.007) compared with those with GDF156months within ± 20% of baseline.. The similarly elevated levels and independent prognostic utility of GDF15 in HFrEF and HFpEF suggest that beyond haemodynamic stress (NT-proBNP), inflammatory injury (GDF15) may play an important role in both HF syndromes.

Topics: Aged; Biomarkers; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Proportional Hazards Models; ROC Curve; Singapore; Stroke Volume; Survival Analysis

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Inflammation; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Outpatients; Prognosis; Risk Assessment; Risk Factors; Time Factors

Topics: C-Reactive Protein; Female; Growth Differentiation Factor 15; Humans; Inflammation; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Outpatients; Risk Assessment

Nasal polyps (NP) are a chronic inflammatory disease of the nasal mucosa; their etiology is suspected to involve oxidative stress. Growth differentiation factor-15 (GDF-15), brain natriuretic peptide (BNP), and ischemia-modified albumin (IMA) are biomarkers used especially in the early diagnosis and follow-up of cardiovascular diseases. The aim of this study was to assess levels of serum GDF-15, BNP, and IMA in patients with NP and to compare them with those of healthy subjects.. This was a prospective study enrolling 41 patients with NP and 48 healthy controls, all aged 18-65 years and referred to the Department of Otorhinolaryngology, Head and Neck Surgery, between January 2014 and February 2015. After a 12-h fast, venous blood (3mL) was drawn and centrifuged (3000rpm, 10min) to collect serum. Blood samples were drawn before endoscopic sinus surgery in the NP group. Serum GDF-15, BNP, and IMA levels were measured.. GDF-15, BNP, and IMA levels of patients with NP were statistically significantly higher than in controls and GDF-15 values were higher than the normal upper limit. GDF-15, BNP, and IMA levels were significantly correlated in both groups.. As GDF-15 is a marker of chronic inflammation and oxidative stress, our finding of increased serum GDF-15 in patients with NP supports the hypothesis that its pathogenesis involves chronic inflammation and oxidative stress.

Topics: Adolescent; Adult; Aged; Biomarkers; Case-Control Studies; Female; Growth Differentiation Factor 15; Humans; Inflammation; Male; Middle Aged; Nasal Polyps; Natriuretic Peptide, Brain; Oxidative Stress; Prospective Studies; Serum Albumin; Serum Albumin, Human; Young Adult

Inflammation may contribute to an increase in cardiac wall stress through pathways related to cardiac remodeling. Cardiac remodeling is characterized by myocyte hypertrophy, myocyte death and modifications of the extracellular matrix. We sought to explore associations among cardiac remodeling, inflammation and myocardial cell injury in a bi-ethnic cohort of South African men and women. We included 165 men (76 African and 89 Caucasian) and 174 women (80 African and 94 Caucasian) between 20 and 65 years of age. Inflammatory markers used were C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-α), whereas troponin T (Trop T) and the N-terminal of pro B-type natriuretic peptide (NT-proBNP) were used as cardiac markers. The frequency of ischemic events (ST segment depression) and left ventricular strain (left ventricular hypertrophy: LVH) were monitored by a 24-h recording of ambulatory blood pressure (BP), ECG and 12-lead standard ECG. Hypertension diagnosed with ambulatory monitoring was more frequent in Africans (53.85 vs. 24.59%; P<0.001), as was the number of ischemic events (6±15 (1; 5) vs. 3±6 (0; 3)). Inflammatory markers (CRP, IL-6 and TNF-α) and the degree of LVH were all significantly higher in Africans (P<0.05). BP was associated (P<0.05) with Trop T in men across ethnic groups. In African men, cardiac stress (NT-proBNP) was associated with TNF-alpha (P<0.001), Trop T (P<0.001) and pulse pressure (P=0.048; adjusted R(2)=0.45). The susceptibility for cardiac wall remodeling appears to increase with hyperpulsatile pressure, low-grade systemic inflammation and ventricular stress, and may lead to the development of future cardiovascular events in African men.

Topics: Adult; Aged; Biomarkers; Black People; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sex Factors; Troponin T; Tumor Necrosis Factor-alpha; Ventricular Remodeling; White People; Young Adult

Coronary plaque rupture mediating acute ST segment elevation myocardial infarction (STEMI) is associated with a systemic inflammatory response. Whether early temporal changes in inflammatory biomarkers are associated with angiographic and electrocardiographic markers of reperfusion and subsequent clinical outcomes is unclear. In the APEX-AMI biomarker substudy, 376 patients with STEMI had inflammatory biomarkers measured at the time of hospital presentation and 24 h later. The primary outcome was the 90-day composite of death, shock, or heart failure. Secondary reperfusion outcomes were (1) worst least residual ST segment elevation (ST-E: <1 mm, 1 to <2 mm, ≥2 mm) and (2) post-percutaneous coronary intervention (PCI) TIMI flow grade (0/1/2 vs 3) and TIMI myocardial perfusion grade (TMPG 0/1 vs 2/3). The 90-day incidence of death, shock or heart failure was 21.3 % in this cohort. Electrocardiographic reperfusion (worst residual ST-E <1 mm, 1 to <2 mm, ≥2 mm) was associated with differences in 24 h change in N-terminal proB-type natriuretic peptide (NT-proBNP) (1192.8, 1332.5, 1859.0 ng/mL; p = 0.043) and the pro-inflammatory cytokines Interleukin (IL)-6 (14.0, 13.6, 22.1 pg/mL; p = 0.016), IL-12 (-0.5, -0.9, -0.1 pg/mL; p = 0.013), and tumor necrosis factor α (TNFα) (1.0, 0.6, 3.6 pg/mL; p = 0.023). Angiographic reperfusion (TMPG 0/1 vs 2/3) was associated with changes in median NT-proBNP (2649.3, 1382.7 ng/mL; p = 0.002) and IL-6 (28.7, 15.1; p = 0.040). After adjustment for baseline covariates, the 24 h change in the pro-inflammatory cytokine TNFα [hazard ratio (HR) 0.49; 95 % CI 0.26-0.95; p = 0.035] and the anti-inflammatory cytokine IL 10 (HR 1.41; 95 % CI 1.06-1.87; p = 0.018) were independently associated with the primary composite outcome. Successful coronary reperfusion was associated with less systemic inflammatory response and greater temporal inflammatory changes were independently associated with higher 90-day composite of death, shock, or heart failure. These findings provide support for an association between success of reperfusion, an acute STEMI inflammatory response and subsequent clinical outcomes.

Topics: Biomarkers; Cohort Studies; Coronary Angiography; Electrocardiography; Heart Failure; Humans; Inflammation; Interleukin-10; Interleukin-6; Myocardial Reperfusion; Natriuretic Peptide, Brain; Peptide Fragments; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Glucose; C-Reactive Protein; Connective Tissue Growth Factor; Diabetes Mellitus, Type 2; Down-Regulation; Echocardiography; Electrocardiography; Fibrosis; Glucose Tolerance Test; Glycosuria; Hypertrophy, Left Ventricular; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Interleukin-1beta; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha; Tyrosine; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Topics: Atrophy; Biomarkers; Brain; Cardiovascular Diseases; Cognitive Dysfunction; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments

Doxorubicin (DOX) remains the most effective anticancer agent which is widely used in several adult and pediatric cancers, but its application is limited for its cardiotoxicity and hepatotoxicity. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for many diseases. In this study, we found that intraperitoneal injection of hydrogen-rich saline (H

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Doxorubicin; Echocardiography; Heart; Heart Injuries; Hydrogen; Inflammation; Male; Malondialdehyde; Natriuretic Peptide, Brain; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Serum Albumin; Sodium Chloride

Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages and have a high prevalence of accelerated atherosclerosis, inflammation and endothelial dysfunction. Nontraditional cardiovascular risk factors and serum cardiac biomarkers would contribute to explain this increased morbidity.. The aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD patients.. In 50 patients with CKD in stage 2/3 kidney disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy controls, the following parameters were measured: cardiac markers (cTnT and NT-proBNP), renal function, inflammatory markers (CRP, serum ferritin and fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT and baFMD.. In our study, we showed an increase of NT-proBNP and the serum cTnT, of serum uric acid and homocysteine with a positive correlation with the increase of cIMT and LVMI and reduced baFMD compared with the controls.. Serum cardiac biomarkers and nontraditional cardiovascular risk factors increase already in the stage 2/3 KDOQI contributing to explain the high cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to have a rise earlier compared with serum cTnT; however, both seemed to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in CKD patients.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Endothelium, Vascular; Female; Humans; Inflammation; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Acuity; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events.. Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement.. During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer.. Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies.

Topics: Aged; Aged, 80 and over; Biomarkers; Fatty Acid-Binding Proteins; Female; Humans; Inflammation; Ischemic Attack, Transient; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Tumor Necrosis Factor-alpha; von Willebrand Factor

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

The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support.. We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group.. Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-β increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline.. Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chemokine CCL2; Female; Heart Failure; Heart-Assist Devices; Humans; Inflammation; Interleukin-18; Interleukin-8; Longitudinal Studies; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Tumor Necrosis Factor-alpha; Ventricular Function, Left

The pathogenesis of abdominal aortic aneurysm (AAA) is complex. Cross-sectional studies have connected circulating biomarkers with AAA, but prospective evidence is limited.. In the Atherosclerosis Risk in Communities Study cohort, we measured multiple blood biomarkers of inflammation, hemostasis, thrombin generation, cardiac dysfunction, and vascular stiffness and identified incident AAAs during follow-up using hospital discharge codes. Six biomarkers (white blood cell count, fibrinogen, D-dimer, troponin T, N-terminal pro-brain natriuretic peptide, and high-sensitivity C-reactive protein) were strongly associated positively with AAA incidence. Compared with having none of these 6 biomarkers in the highest quartile, the hazard ratios of AAA for those with 1, 2, 3, or 4 to 6 biomarkers in the highest quartile were 2.2, 3.3, 4.0, and 9.9, respectively (P for trend < 0.0001) after adjustment for other risk factors.. This prospective study found that higher concentrations of 6 biomarkers were associated with increased risk of AAA. The more markers that fell into the highest quartile, the higher the AAA risk was. Multiple positive biomarkers identify a subgroup of patients at high risk of AAA.

Topics: Aortic Aneurysm, Abdominal; Atherosclerosis; Biomarkers; Blood Proteins; Female; Follow-Up Studies; Humans; Incidence; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Risk; Ultrasonography; United States

Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups.. This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy patients (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS.. A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ, IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status.. Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Donors; Case-Control Studies; Chagas Cardiomyopathy; Chemokines; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Female; Humans; Infant; Infant, Newborn; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasminogen Activator Inhibitor 1; Retrospective Studies; Trypanosoma cruzi; Young Adult

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

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

Brain natriuretic peptide (BNP) has a protective effect on acute injury of the heart, brain, and lung. However, its role in acute kidney injury (AKI) remains unclear. The aim of this study was to investigate the effect of lyophilized recombinant human BNP (lrh-BNP) on AKI and the underlying molecular mechanisms. An experimental model for AKI was established using an ischemia/reperfusion (I/R) procedure. Healthy adult BALB/c mice were randomized to the sham, I/R, and lrh-BNP-treated post-I/R (BNP + I/R) groups. Post-operatively, the BNP + I/R group was subcutaneously injected with lrh-BNP (0.03 μg·kg(-1)·min(-1)), whereas the other groups received saline at the same dose. Serum creatinine (Scr) and blood urea nitrogen levels were examined; tissue staining was performed to evaluate the degree of I/R injury (IRI). Ki67 positive staining of renal tubular epithelial cells was observed using immunofluorescence confocal laser scanning to assess the effect of BNP on cell proliferation after IRI. Inflammatory factor expression levels were detected to evaluate the effect of BNP on renal inflammation. Compared with the sham group, the I/R group showed increased Scr levels, severe tubular injury of the renal outer medulla, increased Kim-1 mRNA expression, an increased number of infiltrative macrophages in the renal interstitium, and increased TNF-α, IL- 1β, IL-6, MCP-1, and HIF-1α mRNA expression. BNP delivery significantly reduced all pathological changes in the I/R group. The protective role of BNP in murine renal IRI may be associated with its inhibition of renal interstitial inflammation and hypoxia and its promotion of renal tubule repair.

Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Epithelium; Humans; Hypoxia; Inflammation; Kidney Function Tests; Kidney Tubules; Male; Mice; Natriuretic Peptide, Brain; Protective Agents; Recombinant Proteins; Reperfusion Injury

Proinflammatory cytokines play a pathogenic role in congestive heart failure. In this study, the effect of peritoneal dialysis treatment on inflammatory cytokines levels in refractory congestive heart failure patients was investigated. During the treatment, the patients reached a well-tolerated edema-free state and demonstrated significant improvement in NYHA functional class. Brain natriuretic peptide decreased significantly after 3 months of treatment and remained stable at 6 months. C-reactive protein, a plasma marker of inflammation, decreased significantly following the treatment. Circulating inflammatory cytokines TNF-α and IL-6 decreased significantly after 3 months of peritoneal dialysis treatment and remained low at 6 months. The reduction in circulating inflammatory cytokines levels may be partly responsible for the efficacy of peritoneal dialysis for refractory congestive heart failure.

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Tumor Necrosis Factor-alpha

Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.. In chronic HF patients (n = 81, 76 ± 9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n = 17, 75 ± 11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r = 0.363, P < 0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

Topics: Aged; Aged, 80 and over; Albumins; Biomarkers; C-Reactive Protein; Ceruloplasmin; Chronic Disease; Cross-Sectional Studies; Female; Halogenation; Heart Failure; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peroxidase

Advanced chronic kidney disease (CKD) leads to complications such as anemia, electrolyte abnormalities, bone and mineral disorder, and malnutrition-inflammation-atherosclerosis (MIA) syndrome, that result in high cardiovascu- lar mortality. One of the biomarkers associated with inflammation and cardiovascular events is pregnancy-associated plasma protein A (PAPP-A). The aim of the study was to measure serum PAPP-A in hemodialyzed CKD patients, and to investigate its correlations with the laboratory markers of the complications. We enrolled 78 consecutive stable adult CKD patients treated with maintenance hemodialysis for median period of 60 months. PAPP-A concentrations were measured with by electrochemiluminescence immunoassay. Average serum PAPP-A in hemodialyzed patients was almost two times higher than the upper reference limit. It positively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), serum sodium, and the markers of inflammation and malnutrition. In conclusion, serum PAPP-A seems a useful biomarker associated with cardiovascular dysfunction, inflammatory state and malnutrition in hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Inflammation; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Pregnancy-Associated Plasma Protein-A; Renal Dialysis; Risk Assessment

We aimed to investigate whether nuclear factor kappa-B activation, as evaluated by gene expression of its inhibitor (I-κBα) and cytokine serum levels, was associated with myocardial dysfunction and mortality in children with septic shock. Twenty children with septic shock were prospectively enrolled and grouped according to ejection fraction (EF) <45% (group 1) or EF ≥45% (group 2) on the first day after admission to the pediatric intensive care unit. No interventions were made. In the first day, patients from group 1 (n = 6) exhibited significantly greater tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10 plasma levels. However, I-κBα gene expression was not different in both groups. Mortality and number of complications were significantly greater in group 1. Patients who died had greater plasma concentrations of TNF-α. In conclusion, TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children, and TNF-α is associated with mortality.

Topics: Adolescent; Biomarkers; Cardiomyopathies; Child; Child, Preschool; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Hemodynamics; Humans; Infant; Inflammation; Intensive Care Units, Pediatric; Interleukin-10; Longitudinal Studies; Male; Natriuretic Peptide, Brain; NF-kappa B; Prospective Studies; Shock, Septic; Tumor Necrosis Factor-alpha

To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates.. The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls.. We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs). Seventy-one patients with RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP concentrations were significantly higher in the total cohort of patients with RA (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In addition, both the total cohort of patients with RA and the subgroup free of CV risk factors were more likely to have levels above the cutoff concentrations of HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p < 0.0001, respectively) than controls. Patients with RA and increased C-reactive protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02) concentrations. HS-cTnT levels positively correlated with the 28-joint Disease Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression analysis indicated that increased HS-cTnT levels were independently associated with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6-35.5) and a body mass index > 30 kg/m(2) (OR 2.7; 95% CI 1.3-5.5).. HS-cTnT and NTproBNP are increased in patients with RA, independent of CV risk factors. The association between HS-cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and disease activity, support the link between myocardial injury/dysfunction and inflammation.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Severity of Illness Index; Troponin T

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

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Cohort Studies; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

A recent study by Mishra and Hoon identified B-type natriuretic peptide (BNP) as an important peptide for itch transmission and proposed that BNP activates spinal natriuretic peptide receptor-A (NPRA) expressing neurons, which release gastrin releasing peptide (GRP) to activate GRP receptor (GRPR) expressing neurons to relay itch information from the periphery to the brain (Science 340:968-971, 2013). A central premise for the validity of this novel pathway is the absence of GRP in the dorsal root ganglion (DRG) neurons. To this end, they showed that Grp mRNA in DRG neurons is either absent or barely detectable and claimed that BNP but not GRP is a major neurotransmitter for itch in pruriceptors. They showed that NPRA immunostaining is perfectly co-localized with Grp-eGFP in the spinal cord, and a few acute pain behaviors in Nppb-/- mice were tested. They claimed that BNP is an itch-selective peptide that acts as the first station of a dedicated neuronal pathway comprising a GRP-GRPR cascade for itch. However, our studies, along with the others, do not support their claims.. We were unable to reproduce the immunostaining of BNP and NPRA as shown by Mishra and Hoon. By contrast, we were able to detect Grp mRNA in DRGs using in situ hybridization and real time RT-PCR. We show that the expression pattern of Grp mRNA is comparable to that of GRP protein in DRGs. Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching behavior. We show that BNP inhibits inflammatory pain and morphine analgesia.. Accumulating evidence demonstrates that GRP is a key neurotransmitter in pruriceptors for mediating histamine-independent itch. BNP-NPRA signaling is involved in both itch and pain and does not function upstream of the GRP-GRPR dedicated neuronal pathway. The site of BNP action in itch and pain and its relationship with GRP remain to be clarified.

Topics: Animals; Ganglia, Spinal; Gastrin-Releasing Peptide; Gene Expression Regulation; Inflammation; Male; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Pain; Pruritus; Receptors, Atrial Natriuretic Factor; Receptors, Bombesin; RNA, Messenger; Signal Transduction; Spinal Cord

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

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

Biomarkers have become an increasingly important tool in clinical practice, helping to improve patient care. In heart failure (HF), brain natriuretic peptide and N-terminal prohormone of the brain natriuretic peptide have been widely applied in prognosis, clinical diagnosis and treatment. Recently, several novel biomarkers have been examined on their efficacy to improve diagnosis, determine the pathophysiologic state of HF, improve clinical decision making, clinical outcome, guide treatment and assess prognosis of HF patients. In this special report, the authors summarize the usefulness and significance of the most promising novel biomarkers in patients with HF.

Topics: Biomarkers; Heart Failure; Humans; Inflammation; MicroRNAs; Natriuretic Peptide, Brain; Prognosis

To examine associations between habitual physical activity (PA) and changes in PA and onset of coronary heart disease (CHD) and the pathways linking PA to CHD.. British Regional Heart Study population-based cohort; men completed questionnaires in 1996 and 1998 to 2000, attended rescreen in 1998 to 2000, and were followed up to June 2010.. Community.. Of 4,252 men recruited from primary care centers (77% of those invited and eligible) who were rescreened in 1998 to 2000, 3,320 were ambulatory and free from CHD, stroke, and heart failure and participated in the current study.. Usual PA (regular walking and cycling, recreational activity and sport). Outcome was first fatal or nonfatal myocardial infarction.. In 3,320 ambulatory men, 303 first and 184 fatal CHD events occurred during a median of 11 years of follow-up; 9% reported no usual PA, 23% occasional PA, and 68% light or more-intense PA. PA was inversely associated with novel risk markers C-reactive protein, D-dimer, von Willebrand Factor and N-terminal pro-brain natriuretic peptide (NT-proBNP). Compared with no usual PA, hazard ratios (HRs) for CHD events, adjusted for age and region, were 0.52 (95% confidence interval (CI) = 0.34-0.79) for occasional PA, 0.47 (95% CI = 0.30-0.74) for light PA, 0.51 (95% CI = 0.32-0.82) for moderate PA, and 0.44 (95% CI = 0.29-0.65) for moderately vigorous or vigorous PA (P for linear trend = .004). Adjustment for established and novel risk markers somewhat attenuated HRs and abolished linear trends. Compared with men who remained inactive, men who maintained at least light PA had an HR for CHD events of 0.73 (95% CI = 0.53-1.02) and men whose PA level increased had an HR of 0.86 (95% CI = 0.55-1.35).. Even light PA was associated with significantly lower risk of CHD events in healthy older men, partly through inflammatory and hemostatic mechanisms and cardiac function (NT-proBNP).

Topics: Adult; Age Factors; Age of Onset; Aged; Aging; Biomarkers; Cause of Death; Coronary Disease; Follow-Up Studies; Hemostasis; Humans; Inflammation; Male; Middle Aged; Morbidity; Motor Activity; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Risk Factors; Surveys and Questionnaires; Survival Rate; Time Factors; United Kingdom

Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH).. Plasma YKL-40 levels were measured in 82 IPAH patients without current or previous PAH-specific treatment during right heart catheterization and in 54 healthy volunteers. Concurrent data included clinical, haemodynamic and biochemical variables.. Plasma YKL-40 levels were increased in IPAH patients compared with control subjects (median, interquartile range: IPAH: 24.90, 17.68-39.78 ng/mL; controls: 16.58, 14.20-19.64 ng/mL; P < 0.001). YKL-40 levels correlated with cardiac index (r = -0.244, P = 0.027) and N-terminal pro-brain natriuretic peptide (NT-proBNP, r = 0.263, P = 0.017). After a median follow-up of 578 days, YKL-40 outperformed NT-proBNP, uric acid, and 6-min walk distance in receiver operating characteristic (ROC) analyses in predicting both clinical worsening (area under the curve (AUC) 0.681) and death (AUC 0.717). Compared with patients with YKL-40 below the ROC-derived cut-off point (24.5 ng/mL), the high YKL-40 group showed higher pulmonary vascular resistance and serum uric acid levels, and showed more clinical worsening events and deaths in Kaplan-Meier analyses. Plasma YKL-40 was independently associated with clinical worsening in univariate and multivariate Cox analyses (all P < 0.05).. Plasma YKL-40 might serve as a promising indicator of disease severity and prognosis in patients with IPAH.

Topics: Adipokines; Adult; Biomarkers; Cardiac Catheterization; China; Chitinase-3-Like Protein 1; Disease Management; Disease Progression; Familial Primary Pulmonary Hypertension; Female; Humans; Inflammation; Kaplan-Meier Estimate; Lectins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Pulmonary Circulation; Reproducibility of Results; ROC Curve

Heart failure (HF) is a common, debilitating disorder in which the heart is unable to pump an adequate blood supply to the tissues. Although it has been shown that inflammation occurs in HF, inflammatory markers have yet to be defined. Inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), cytokines and serum sialic acid (SA) have been suggested as cardiovascular risk biomarkers. This study aims to assess the serum levels of inflammatory markers such as sialic acid and hs-CRP in chronic heart failure (CHF). Forty-eight patients with CHF and 30 healthy controls were recruited. Total sialic acid (TSA) and lipid-associated sialic acid (LASA), and the inflammatory marker hs-CRP, were assayed in all study subjects. N-terminal pro-brain natriuretic peptide (NT-proBNP) was assayed in the patient group only. Serum mean TSA and LASA were significantly higher in CHF patients when compared to healthy controls (P < 0.01). Mean hs-CRP levels in CHF patients showed a significant elevation compared with healthy controls (P < 0.01). There was a significant positive correlation between TSA and hs-CRP. Thus, TSA and hs-CRP would appear to be stable markers of systemic inflammation in chronic heart failure.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; N-Acetylneuraminic Acid; Natriuretic Peptide, Brain; Peptide Fragments

Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from pre-CRT implantation to 14months follow-up in CRT-responders and nonresponders, defined by two response criteria.. We studied 105 heart failure patients implanted with a CRT-defibrillator (68% men; age=65.4±10.1years). The objective CRT-response was defined as a reduction of ⩾15% in left ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points.. Pre-implantation concentrations of TNFα were significantly lower for subjective responders compared to nonresponders (p=.05), but there was no difference in BNP and the other inflammatory markers at baseline. Objective CRT-response was significantly associated with lower BNP levels over time (F=27.31, p<.001), and subjective CRT-response with lower TNFα levels (F=5.67, p=.019).. Objective and subjective response to CRT was associated with lower levels of BNP and TNFα, respectively, but not with other markers of inflammation. This indicates that response to CRT is not automatically related to a stronger overall decrease in inflammation. Large-scale studies are warranted that further examine the relation between the clinical effects of CRT on inflammatory markers, as the latter have been associated with poor prognosis in heart failure.

Topics: Aged; Biomarkers; Cardiac Resynchronization Therapy; Cytokines; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Surveys and Questionnaires; Treatment Outcome

Increasing attention is being paid towards reducing short-term heart failure readmissions in recent years. Biomarkers such as galectin-3 are likely to play pivotal roles in future heart failure management strategies as they can provide objective information on various pathophysiologic processes involved in heart failure. Galectin-3 is a biomarker of inflammation and fibrosis, which is strongly associated with adverse remodeling of the myocardium and subsequent left ventricular dysfunction. Clinically, elevated galectin-3 levels are associated with increased risk for short- and long-term risk for mortality and heart failure readmission. Galectin-3 can provide incremental predictive value for adverse events over natriuretic peptides. Although significant work is still required to further define the role of galectin-3, it has the potential to become an important part of future heart failure management algorithms by helping to provide an individualized risk profile, which can be used to optimize resource allocation and improve treatment outcomes.

Topics: Acute Coronary Syndrome; Biomarkers; Blood Proteins; Fibrosis; Galectin 3; Galectins; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prognosis; Risk Assessment; Ventricular Remodeling

Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF.. Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%.. It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Coronary Angiography; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume

Topics: Animals; Atrial Natriuretic Factor; Humans; Inflammation; Myocytes, Cardiac; Natriuretic Peptide, Brain

Topics: Animals; Atrial Natriuretic Factor; Humans; Inflammation; Myocytes, Cardiac; Natriuretic Peptide, Brain

Pentraxin 3 (PTX3) is a novel inflammatory marker produced by various cell types including those of the vasculature and the heart. The relationship between inflammatory markers and prognosis of patients with heart failure with normal ejection fraction (HFNEF) remains unknown. We investigated whether plasma PTX3 levels can predict future cardiovascular events in patients with HFNEF.. Plasma PTX3, high-sensitivity C-reactive protein, and B-type natriuretic peptide levels were measured prospectively in 360 stable patients with HFNEF. The subsequent incidence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction (MI), unstable angina pectoris, nonfatal ischemic stroke, hospitalization for heart failure decompensation, and coronary revascularization, was determined. During a mean 30-month follow-up, 106 patients experienced cardiovascular events. These events were more frequent in patients with high plasma PTX3 levels (>3.0 ng/mL) than low levels (≤3.0 ng/mL). Multivariable Cox hazard analysis showed that PTX3 (hazard ratio: 1.16; 95% CI: 1.05 to 1.27; P<0.01) and B-type natriuretic peptide (hazard ratio: 1.08; 95% CI: 1.03 to 1.14; P<0.001), but not high-sensitivity C-reactive protein levels, were significant predictors of future cardiovascular events. Multivariable Cox analysis with the forced inclusion model, including 5 previously identified prognostic factors, found that PTX3 was a significant predictor of cardiovascular events (hazard ratio: 1.16; 95% CI: 1.06 to 1.27; P<0.01). The C-statistics for cardiovascular events substantially increased from 0.617 to 0.683 when PTX3 was added to the 5 previously identified prognostic factors.. High plasma PTX3 levels, but not other inflammatory markers, are correlated with future cardiovascular events in patients with HFNEF. PTX3 may be a useful biomarker for assessment of risk stratification in HFNEF.. http://www.umin.ac.jp; Unique identifier: UMIN000002170.

Topics: Aged; Aged, 80 and over; Angina, Unstable; C-Reactive Protein; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Natriuretic Peptide, Brain; Prognosis; Serum Amyloid P-Component; Stroke; Stroke Volume

To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease.. In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged.. This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

Topics: Adiponectin; Adipose Tissue; Aged; Brachial Artery; Coronary Artery Bypass; Coronary Artery Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Organ Culture Techniques; Organ Specificity; Risk Factors; Subcutaneous Fat; Thigh; Thorax; Tumor Necrosis Factor-alpha; Ultrasonography; Vasodilation; Ventricular Dysfunction, Left

Topics: Adiponectin; Adipose Tissue; Female; Heart Failure; Humans; Inflammation; Male; Myocardial Ischemia; Natriuretic Peptide, Brain

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

YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects.. Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays.. Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = -0.28; P < .05), New York Heart Association functional class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (β = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients.. YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.

Topics: Adipokines; Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Chitinase-3-Like Protein 1; Coronary Disease; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Glycopeptides; Heart Transplantation; Humans; Inflammation; Interleukin-6; Lectins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Transplant Recipients

Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels.. A cross-sectional study of 86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP).. Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels.. More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.

Topics: Cross-Sectional Studies; Endotoxemia; Endotoxins; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Troponin T

To elucidate role of subclinical inflammation in progression of atherosclerotic process in magistral noncoronary arteries in patients during one year after ST-elevation myocardial infarction (MI).. We examined 168 men with MI (mean age 59.5 years). All patients during hospitalization underwent coronary angiography and color duplex scanning of brachiocephalic arteries. In a year ultrasound study of noncoronary vessels was repeated and progression of atherosclerosis assessed. Parameters of inflammation in blood serum were measured on days 10-14 of MI and after one year.. At repeat study most patients demonstrated progression of noncoronary atherosclerosis. Some biomarkers measured during inhospital phase of MI (low concentration of anti-inflammatory interleukin 10 - IL-10, elevated N-terminal pro brain natriuretic peptide) allowed to distinguish group of patients with subsequent progression of noncoronary atherosclerosis. Elevated concentrations of C-reactive protein and 11-10 registered in a year after MI were also associated with more severe progression of atherosclerosis. Serum levels of neopterin and IL-12 remained stable in patients with and decreased in patients without pronounced progression of atherosclerosis.

Topics: Atherosclerosis; Biomarkers; Brachiocephalic Trunk; C-Reactive Protein; Coronary Angiography; Coronary Vessels; Disease Progression; Electrocardiography; Humans; Inflammation; Interleukins; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Neopterin; Peptide Fragments; Risk Factors; Severity of Illness Index; Statistics as Topic; Ultrasonography, Doppler, Color

This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.. We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.. NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.. These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men.

Topics: Adult; Biomarkers; Black People; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Urokinase Plasminogen Activator; Regression Analysis; Solubility; South Africa; White People

Inflammation is a key factor in the long-term outcome of acute coronary syndromes (ACS). The aim of the present study was to evaluate inflammatory markers in patients with ACS as predictors for major adverse cardiovascular events (MACE) and hard events.. This study included 1548 patients with ACS. C-reactive protein (CRP), white blood count (WBC), and their subtypes were analyzed during hospitalization. Receiver operator characteristic (ROC) and Kaplan-Meier survival curves were used to assess the predictive value and hard events (nonfatal myocardial infarction and cardiac death) and MACE (hard events, hospitalization for cardiac causes, late revascularization and stroke) were obtained during 30 days.. ROC analysis of CRP and WBC to predict adverse events revealed cut-offs of 47.5 ng/l and 16.6 × 10/μl for MACE and 93.5 ng/l and 16.6 × 10/μl for hard events. The cumulative adverse event rates were significantly higher in patients with increased CRP (≥47.5 ng/l; 17 versus 4%, P < 0.001) and WBC (≥16.6 × 10/μl; 21 versus 5%, P < 0.001) for MACE and with elevated CRP (≥93.5 ng/l; 16 versus 2%, P < 0.001) and WBC (≥16.6 × 10/μl; 18 versus 2%, P < 0.001) for hard events, demonstrating highest event rates with elevation of both inflammatory markers: (28 versus 5%, P < 0.001) for MACE and (26 versus 2%, P < 0.001) for hard events. Analysis of CRP and WBC further revealed a substantial negative correlation with left ventricular function (P < 0.001). Moreover, markers of myocardial damage were significantly elevated in patients with abnormal CRP or WBC (P < 0.001).. Inflammatory markers such as CRP and WBC alone and, particularly, in combination are strong and independent predictors of outcome in patients with ACS.

Topics: Acute Coronary Syndrome; Biomarkers; C-Reactive Protein; Coronary Angiography; Creatine Kinase; Female; Flow Cytometry; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Survival Rate; Troponin T

A 73-year-old man with a mechanical aortic valve and a history of congestive heart failure was admitted to our hospital with an unspecifically reduced general condition. Physical examination was normal according to age apart from mechanic valve closure tones and a 2/6 sytolic murmur at Erb's point.. Inflammation markers were elevated (leukocytosis 22 100/μl, CRP 22 mg/dl ), there was mild anemia (hemoglobin 9.7 mg/dl) and digitoxin blood level was increased to 56 μg/l (therapeutic range 10-30 μg/l). Because NT-proBNP was highly elevated, further diagnostics focused on cardiac causes of BNP elevation despite missing clinical symptoms. Transesophageal echocardiography was inconspicuous and blood cultures were negative. Therefore an infection of unknown origin or an emerging endocarditis were presumed.. Pragmatic treatment with antibiotics and diuretics as well as discontinuation of digitoxin led to normalization of leukocytes, CRP and digitoxin levels. But the patient's general condition deteriorated further, NT-proBNP rose to 37731 pg/ml and the patient became disoriented. On thorough questioning the patient's relatives stated that he had fallen 6 weeks previously. Computed tomography then revealed a large chronic subdural hematoma which had caused the NT-proBNP elevation. The patient was operated successful.. In patients with elevated BNP and atypical symptoms neurological causes should be considered.

Topics: Aged; Biomarkers; Diagnosis, Differential; Diagnostic Errors; False Positive Reactions; Hematoma, Subdural; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Peptide Fragments

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥ 50 years and with ≥ 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Interleukin-1beta; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Receptors, Interleukin-1 Type II; Serum Amyloid P-Component; Smoking; Spirometry; Ultrasonography; Ventricular Dysfunction, Left

Postoperative-fluid retention is a severe complication frequently reported in patients undergoing major surgical procedures. The complex network of molecules involved in such a severe surgery-induced condition remains poorly understood. Inflammation has been proposed among the various causes of fluid retention. Since TNF-α is one of the main proinflammatory cytokine initially released after major surgery, it is reasonable to assume its involvement in fluid overload. Here, we showed that TNF-α selectively regulates key molecules involved in fluids balance, such as natriuretic peptides (NPs) and aquaporins, in human bronchial epithelial cells BEAS-2B. In particular, we found that TNF-α induced a decrease of arial natriuretic peptide, natriuretic peptide receptor-1, aquaporin-1 and aquaporin-5 and an increase of brain natriuretic peptide with a different involvement of nuclear factor-κB and mitogen-activated protein kinases signaling pathway activation. Moreover, the observed changes in NPs expression, demonstrate inflammation as an additional cause of brain natriuretic peptide elevation, adding an important piece of information in the novel area of study regarding NPs and inflammation. Finally, we suggest that inflammation is one of the mechanisms of Aquaporin-1 and aquaporin-5 expression regulation. Therefore, in this exploratory study, we speculate that TNF-α might be involved in postoperative-fluid retention related to major surgery.

Topics: Aquaporin 1; Aquaporin 5; Atrial Natriuretic Factor; Bronchi; Cell Line; Cell Survival; Culture Media; Dexamethasone; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation; Hemodynamics; Homeostasis; Humans; Inflammation; Natriuretic Peptide, Brain; NF-kappa B; Polymerase Chain Reaction; Receptors, Atrial Natriuretic Factor; Signal Transduction; Tumor Necrosis Factor-alpha

To analyse the relationship between objectively measured daily walking duration and cardiovascular biomarkers of inflammation, cardiac dysfunction and renal impairment.. Between March 2009 and April 2010, physical activity was assessed in 1253 community-dwelling individuals living in Germany aged ≥65 years (57% men) over 1 week using a thigh-worn accelerometer. C reactive protein (CRP), white blood cells (WBC), N-terminal pro-brain natriuretic peptide, high-sensitive troponin T (hsTnT), creatinine (Cr) and cystatin C (CysC) were also measured. Least-square means of daily walking duration were calculated for quartiles of each biomarker adjusted for sex, age, pre-existing cardiovascular disease and smoking status.. After adjustment for covariates, statistically significant linear associations with walking duration were observed for WBC, hsTnT, Cr and CysC. CRP quartiles 1 and 2 showed no significant difference followed by a significant inverse dose-response relationship. A similar pattern, but less pronounced, was seen for N-terminal pro-brain natriuretic peptide. Mean differences between the first two quartiles of CRP and its fourth quartile were 17 min. Between categories 1 (more beneficial) and 4 of WBC, hsTnT, Cr and CysC the differences were 15, 12, 23 and 20 min, respectively.. Increased walking duration is associated with a more favourable profile of cardiovascular biomarkers in elderly subjects.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Female; Germany; Humans; Inflammation; Male; Motor Activity; Natriuretic Peptide, Brain; Peptide Fragments; Population Surveillance; Renal Insufficiency; Risk Factors; Time Factors; Troponin I; Walking

The aim of this study was to evaluate, according to functional response, the neuroendocrine and inflammatory status in patients with chronic heart failure before and after therapy with carvedilol.. Serum tumor necrosis factor-α (TNF-α) soluble receptors (sTNF-R1 and sTNF-R2), interleukin (IL)-10 and IL-18, chromogranin A (CgA) and brain natriuretic peptide (pro-BNP) were measured in 37 New York Heart Association class II to IV heart failure patients, at baseline and after 6 months of therapy with carvedilol. Patients were divided in two groups according to whether, following carvedilol, left-ventricular ejection fraction (LVEF) had increased by at least 5% (17 patients) or not (20 patients). Baseline LVEF was higher in nonresponders (38 ± 5 vs. 31 ± 7%, P = 0.002). In responders, LVEF increased from 31 ± 7 to 51 ± 7% (P < 0.0001), whereas in nonresponders it decreased from 38 ± 5 to 33 ± 7%, (P = 0.02). sTNF-R1 (P = 0.019) and sTNF-R2 (P = 0.025) increased in nonresponders, whereas they did not change in responders. After carvedilol, IL-10 was significantly higher in responders (P = 0.03). Conversely, no significant IL-18 and CgA changes were observed in either group. CgA was not significantly different between groups at baseline and after carvedilol in either group, whereas pro-BNP significantly increased in nonresponders (from 438 ± 582 to 1324 ± 1664 pg/ml, P = 0.04) and decreased in responders (from 848 ± 1221 to 420 ± 530 pg/ml, P = 0.08).. Increased inflammatory activation observed only in heart failure patients not improving left-ventricular function after carvedilol may indicate that inflammation, either as a direct cause or as a consequence, is associated with progressive ventricular dysfunction.

Topics: Adrenergic beta-Antagonists; Aged; Carbazoles; Carvedilol; Cohort Studies; Cytokines; Echocardiography; Female; Heart Failure, Systolic; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Propanolamines; Quality of Life; Severity of Illness Index; Stroke Volume; Treatment Outcome

Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF).. We studied 27 patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically.. CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P=0.001).. Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

Topics: Aged; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Case-Control Studies; Chronic Disease; Echocardiography; Extracellular Matrix; Female; Heart Failure; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Tissue Inhibitor of Metalloproteinase-2; Treatment Outcome; Ventricular Remodeling

The prevalence of cardiac cachexia has previously been estimated to 8-42 %. However, novel treatment strategies for chronic heart failure (CHF) have improved and decreased morbidity and mortality. Therefore, we aimed to reassess the prevalence of cachexia in an outpatient CHF clinic and to characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF <45 %) with cachexia (n = 19) and without (n = 19) were compared to controls with prior myocardial infarction and left ventricular ejection fraction (LVEF) >45 % (n = 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40.6 ± 8.0 % (controls), (P < 0.001). NT-proBNP levels were inversely correlated to abdominal fat in a multivariate linear regression analysis adjusted for known predictors of NT-proBNP (LVEF and NYHA); (β = -0.28; P = 0.018). Myostatin levels were reduced in cachectic CHF compared to controls (P = 0.013). The prevalence of cachexia in stable CHF, treated according to recent guidelines, is lower than previously anticipated. Body alterations in cachexia consist mainly of reduced abdominal fat mass, and its inverse correlation to NT-proBNP suggests involvement of abdominal lipolysis. Our data do not support a role of circulating myostatin as a biomarker for muscle wasting.

Topics: Abdominal Fat; Aged; Aged, 80 and over; Body Composition; Bone Density; Cachexia; Comorbidity; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Myostatin; Natriuretic Peptide, Brain; Parathyroid Hormone; Peptide Fragments; Prevalence

Previous observations suggest that cardiac resynchronization therapy (CRT) may exert an anti-inflammatory effect. The objective of this study was to evaluate the effect of temporary interruption of long-term CRT on plasma concentrations of proinflammatory cytokines and brain natriuretic peptide (BNP). The study group consisted of 54 patients (32 male and 22 female, mean age 64 years) with chronic heart failure (HF) treated with CRT. BNP, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and neopterin were measured three times: after 26-28 weeks of continuous CRT (CRT-on), 48 h after its cessation (CRT-off), and 48 h after switching the CRT-on again. CRT interruption resulted in a significant worsening of left ventricular systolic function: reduction of cardiac output (CO), dP/dt, and left ventricular ejection fraction (LVEF), as well as deterioration of mitral regurgitation in the CRT responder group. A significant increase in serum concentrations of hs-CRP, neopterin, IL-6, and BNP was noted in this subpopulation. In CRT nonresponders, no significant changes were observed. In responders the changes in serum concentrations of hs-CRP, IL-6, neopterin, and BNP, following CRT interruption, significantly correlated with the respective changes in thoracic fluid content (TFC) and inversely correlated with LVEF changes. Even short (48 h) interruption of long-term CRT led to a significant increase of proinflammatory cytokines and BNP concentrations in responders. The changes in hs-CRP, IL-6, neopterin, and BNP concentrations correlated with the change in TFC-marker of pulmonary congestion and inversely correlated with the change in LVEF.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiac Resynchronization Therapy; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Neopterin; Stroke Volume; Time Factors; Treatment Outcome; Up-Regulation; Ventricular Function, Left

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Therefore, we evaluated NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and 6 months after (6M) treatment. At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11 % were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with erythrocyte sedimentation rate (ESR) (p < 0.001), age (p = 0.01), and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. In conclusion, our data suggest that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status.

Topics: Adult; Blood Sedimentation; Echocardiography; Female; Gene Expression Regulation; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Regression Analysis; Risk Factors; Spondylitis, Ankylosing; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

The article discusses the results of detection of activity of matrix metalloproteinase-9, tissue inhibitors of metalloproteinases-4, endotoxin, tumor necrosis factor-alpha, C-reactive protein, sE-selectine in blood of patients with chronic cardiac failure depending on severity of disease. It is demonstrated that progressing of chronic cardiac failure is associated with the increase of level of endotoxemia, activation of systemic inflammation and misbalance in the system of matrix metalloproteinase and tissue inhibitors of metalloproteinase.

Topics: C-Reactive Protein; Chronic Disease; Endotoxins; Female; Heart Failure; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha

Chronic heart failure is often complicated by the development of cachexia with the loss of fat mass. Zinc α2-glycoprotein (ZAG) is a serum adipokine with lipolytic effects in cancer cachexia. We evaluated in patients with advanced heart failure with (CxHF) or without cachexia (nCxHF) the relationship of ZAG with circulating free fatty acid (FFA), as an index of lipolysis, and with other neurohormonal and inflammatory biomarkers. Two groups, nCxHF (n = 46) and CxHF (n = 18), the latter having a documented, involuntary, edema-free loss of body weight of at least 7.5% in the previous 6 months, underwent plasma determination of FFA, ZAG, norepinephrine (NE), tumor necrosis factor-α, and natriuretic peptide levels (atrial natriuretic, B-type natriuretic peptide). The patients were compared with age-matched healthy controls (CTR) (n = 21). Zinc α2-glycoprotein, atrial natriuretic peptide, B-type natriuretic peptide, and tumor necrosis factor-α circulating levels were similarly greater in CxHF and nCxHF than in CTR. Free fatty acid and NE were higher in CxHF than in nCxHF. A positive correlation between FFA and NE was found in both CxHF (r = 0.73, P < .01) and nCxHF (r = 0.48, P < .01) but only in CxHF between ZAG and FFA (r = 0.54, P = .02) and between ZAG and NE (r = 0.70, P < .01). No correlations between natriuretic peptides and ZAG were found. Serum ZAG levels are increased in advanced heart failure patients compared with CTR, without differences between CxHF and nCxHF. Only in CxHF, ZAG levels are directly correlated to circulating levels of FFA and NE, suggesting a close interaction of ZAG with sympathetic-mediated lipolysis.

Topics: Adipokines; Aged; Biomarkers; Body Weight; Cachexia; Case-Control Studies; Fatty Acids, Nonesterified; Female; Heart Failure; Humans; Inflammation; Lipolysis; Male; Natriuretic Peptide, Brain; Neurotransmitter Agents; Seminal Plasma Proteins; Tumor Necrosis Factor-alpha; Zn-Alpha-2-Glycoprotein

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

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

Troponin T (TnT), brain natriuretic peptide (BNP) and its precursor (NT-proBNP) are useful markers of acute coronary events and heart failure. The aim of this study was to analyze the influence of chronic renal failure, inflammation and heart disease in these biomarkers.. In 266 patients with different stages of chronic renal diseases, the following parameters were measured: cardiac markers (TnT, BNP and NT-proBNP), renal function, inflammatory markers (hsCRP, fibrinogen, albumin, uric acid and white blood cells). We recorded the cardiovascular history. Ventricular dysfunction and left ventricular hypertrophy were assessed by echocardiography.. A significant correlation between cardiac markers and inflammatory parameters such as fibrinogen, hsCRP and albumin was found. Age (OR 1.05, P = .021), serum albumin (OR: 0.06, P=.006), ischemic heart disease (OR: 8.17, P=.0092) and renal failure (OR: 1.67, P=.05) were predictors of higher BNP levels. Age (OR 1.05, P=.0097), serum albumin (OR: 0.12, P=.001), ischemic heart disease (OR: 3.43, P=.034), renal failure (OR: 1, 65, P=.036) and heart failure (OR: 4.33, P=.0312) were predictors of elevated NT-proBNP. Previous ischemic heart disease alone increased TnT levels (OR: 6.51, P=.0012).. Age, previous cardiac disease and inflammation increase cardiac marker levels in patients with different stages of renal disease, but the degree of renal failure is an important factor influencing NT-proBNP levels. However, ischemic heart disease alone increases the levels of TnT.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Female; Heart Diseases; Humans; Inflammation; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Severity of Illness Index; Troponin T; Ultrasonography

We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.. Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.. We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.. Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).. ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.

Topics: Acetanilides; Acute Coronary Syndrome; Aged; Biomarkers; Cardiovascular Diseases; Electrocardiography; Female; Heart Failure; Hemodynamics; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Male; Natriuretic Peptide, Brain; Piperazines; Prognosis; Randomized Controlled Trials as Topic; Ranolazine; Receptors, Cell Surface; Risk Assessment

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

Despite progress in management of patients with heart failure (HF) these patients still have a poor prognosis. We tested the hypothesis whether the inflammatory biomarker YKL-40 alone or in combination with high-sensitivity C-reactive protein (hs-CRP) and/or N-terminal-pro-B natriuretic peptide (NT-proBNP) could be a new prognostic biomarker for all-cause mortality in patients with HF.. A total of 717 of the 1000 patients with severe left ventricular systolic dysfunction included in the EchoCardiography and Heart Outcome Study were included in Denmark and had blood sample available for serum YKL-40 determination. Mean age of patients was 70 years, and 73% were male. During the 7 years follow-up period 458 patients died. Patients were categorised according to serum YKL-40 at entry into four quartiles: quartile I with median serum YKL-40=60 μg/L (5-95% Confidence interval (CI): 30-82), quartile II: YKL-40=107 μg/L (CI: 86-132), quartile III: YKL-40=169 μg/L (CI: 142-221), and quartile IV: YKL-40=286 μg/L (CI: 230-770). Hazard ratios for all-cause mortality were with quartile I as reference 1.33 (CI: 0.99-1.80), 1.35 (CI: 0.99-1.82), and 1.54 (CI: 1.14-2.08) for serum YKL-40 II to IV quartiles, respectively following multivariable adjustment for cardiovascular risk factors (age, left ventricular ejection fraction, gender, history of heart failure, ischemic heart disease, chronic pulmonary disease, diabetes mellitus, stroke, hypertension, NT-proBNP, hs-CRP, and renal function).. Serum YKL-40 is significantly associated with all-cause mortality in patients with HF and could potentially be a new prognostic biomarker in these patients.

Topics: Adipokines; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Chitinase-3-Like Protein 1; Female; Follow-Up Studies; Heart Failure; Humans; Inflammation; Lectins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Research Design; Survival Analysis; Ventricular Dysfunction, Left

We investigated the expression and secretion of the natriuretic peptides (NPs) ANF and BNP in lipopolysaccharide (LPS)-induced sepsis and its association with cytokines and other biologically active substances. LPS treatment increased plasma levels of ANF and BNP. The latter increase was larger than the increase in plasma ANF. LPS also increased cardiac content and gene expression of BNP but not of ANF. LPS treatment significantly increased gene expression cytokines, chemokines and proteases, which significantly correlated with BNP gene expression. SB203580, a p38 MAP kinase inhibitor, inhibited the elevation of BNP in plasma. The present work suggests that during inflammation, BNP gene expression and secretion is uniquely related to changes in gene expression in the absence of hemodynamic changes and hence differentiates ANF and BNP as biomarkers of cardiac disease.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cytokines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Imidazoles; Inflammation; Lipopolysaccharides; Myocardium; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Pyridines; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction

α-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of α-defensins in CHF patients and healthy controls and to examine the predictive ability of α-defensins, alone and combined with N-terminal pro brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality.. In a prospective observational study lasting 2.6 years we examined the prognostic value of plasma α-defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. α-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III-IV than in patients in NYHA class I-II and healthy controls (P = 0.001). The absolute increase in risk of mortality for patients with α-defensin levels in the upper tertile vs. the lowest tertile was 30% (P = 0.002). After adjusting for potential confounders including NT-proBNP, plasma α-defensins remained independently associated with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed α-defensin values. The combination of high α-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure.. Plasma α-defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.

Topics: Aged; alpha-Defensins; Analysis of Variance; Biomarkers; C-Reactive Protein; Case-Control Studies; Confidence Intervals; Denmark; Female; Heart Failure; Humans; Inflammation; Linear Models; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Statistics as Topic; Statistics, Nonparametric; Survival Analysis; Treatment Outcome

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

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

Mobilization of stem cells in acute MI might signify the reparatory response. Aim of the Study. Prospective evaluation of correlation between CD34+CXCR4+ cell mobilization and improvement of LVEF and remodeling in patients with acute MI in 1-year followup. Methods. 50 patients with MI, 28 with stable angina (SAP), and 20 individuals with no CAD (CTRL). CD34+CXCR4+ cells, SDF-1, G-CSF, troponin I (TnI) and NT-proBNP were measured on admission and 1 year after MI. Echocardiography and ergospirometry were carried out after 1 year. Results. Number of CD34+CXCR4+ cells in acute MI was significantly higher in comparison with SAP and CTRL, but lower in patients with decreased LVEF ≤40%. In patients who had significant LVEF increase ≥5% in 1 year FU the number of cells in acute MI was significantly higher versus patients with no LVEF improvement. Number of cells was positively correlated (r = 0,41, P = 0,031) with absolute LVEF change and inversely with absolute change of ESD and EDD in 1-year FU. Mobilization of CD34+CXCR4+ cells in acute MI was negatively correlated with maximum TnI and NT-proBNP levels. Conclusion. Mobilization of CD34+CXCR4+ cells in acute MI shows significant positive correlation with improvement of LVEF after 1 year.

Topics: Aged; Antigens, CD34; Chemokine CXCL12; Echocardiography; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Receptors, CXCR4; Stem Cells; Time Factors; Troponin I; Ventricular Function, Left; Ventricular Remodeling

Therapeutic plasma exchange (TPE) plays a key role in the management of various diseases, from thrombotic thrombocytopenic purpura and Goodpasture's syndrome to cardiac allograft rejection. In many of these disease states cardiac and inflammatory involvement is common and biomarkers are routinely used for diagnosis or assessment of therapeutic success. The effect of TPE on biomarkers used in the clinical routine has not been investigated.. TPE was initiated for established clinical conditions in 21 patients. Troponin T, NT-proBNP, C-reactive protein, procalcitonin and routine chemistry were drawn before and after TPE, as well as before and after the 2(nd) TPE. The total amount of these markers in the waste bag was also analyzed.. In 21 patients 42 TPEs were performed. The procedure reduced plasma levels of the examined biomarkers: 23% for NT-proBNP (pre vs. post: 4637±10234 ng/l to 3565±8295 ng/l, p<0.001), 64% for CRP (21.9±47.0 mg/l vs. 7.8±15.8 mg/l, p<0.001) and 31% for procalcitonin (0.39±1.1 µg/l vs. 0.27±0.72 µg/l, p=0.004). TPE also tended to reduce plasma levels of troponin T by about 14% (60.7±175.5 ng/l vs. 52.2±141.3 ng/l), however this difference was not statistical significant (p=0.95). There was a significant correlation between the difference of pre TPE levels to post TPE levels of all examined biomarkers and the total amount of the removed biomarker in the collected removed plasma.. TPE significantly reduces plasma levels of inflammatory and cardiac biomarkers. Therefore, post TPE levels of cardiac and inflammatory biomarkers should be viewed with caution.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Heart Diseases; Humans; Inflammation; Kinetics; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Exchange; Protein Precursors; Time Factors; Troponin T

Tako-Tsubo cardiomyopathy (TTC) is associated with regional left ventricular dysfunction, independent of the presence of fixed coronary artery disease. Previous studies have used T2-weighted cardiac MRI to demonstrate the presence of periapical oedema. The authors sought to determine the distribution, resolution and correlates of oedema in TTC.. 32 patients with TTC were evaluated at a median of 2 days after presentation, along with 10 age-matched female controls. Extent of oedema was quantified both regionally and globally; scanning was repeated in patients with TTC after 3 months. Correlations were sought between oedema and the extent of hypokinesis, catecholamine release, release of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and markers of systemic inflammatory activation (high-sensitivity C-reactive protein and platelet response to nitric oxide).. In the acute phase of TTC, T2-weighted signal intensity was greater at the apex than at the base (p<0.0001) but was nevertheless significantly elevated at the base (p<0.0001), relative to control values. Over 3 months, T2-weighted signal decreased substantially, but remained abnormally elevated (p<0.02). The regional extent of oedema correlated inversely with radial myocardial strain (except at the apex). There were also direct correlations between global T2-weighted signal and (1) plasma normetanephrine (r=0.39, p=0.04) and (2) peak NT-proBNP (r=0.39, p=0.03), but not with systemic inflammatory markers.. TTC is associated with slowly resolving global myocardial oedema, the acute extent of which correlates with regional contractile disturbance and acute release of both catecholamines and NT-proBNP.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Case-Control Studies; Edema; Female; Humans; Inflammation; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Normetanephrine; Peptide Fragments; Takotsubo Cardiomyopathy

Doxorubicin [(DOX) Adriamycin] is an effective anticancer agent whose major limiting side effect is cardiotoxicity. This cardiotoxicity is predicted only by the cumulative dose of DOX where the clinical situation involves chronic drug administration. Therefore, we investigate the effect of chronic DOX cardiotoxicity on expression of the cardiac cytochrome P450 (P450) enzymes and arachidonic acid (AA) metabolism in male Sprague-Dawley (SD) rats. The chronic toxicity was induced by multiple intraperitoneal injections for a cumulative dose of 15 mg/kg divided into six injections within 2 weeks. After 14 days of the last injection, the heart, liver, and kidney were harvested, and the expression of different genes was determined by real-time polymerase chain reaction. In addition, microsomal protein from the heart was prepared and incubated with AA. Thereafter, different AA metabolites were analyzed by liquid chromatography-electrospray ionization-mass spectrometry. The chronic DOX cardiotoxicity significantly induced gene expression of hypertrophic markers, apoptotic markers, CYP2E1, CYP4A3, CYP4F1, CYP4F5, and soluble epoxide hydrolase (sEH) enzyme, which was accompanied by an increase in the activity of P450 ω-hydroxylases and sEH. In addition, both the sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid, and the ω-hydroxylase inhibitor, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016), significantly prevented the DOX-mediated induction of the hypertrophic markers in the cardiac-derived H9c2 cells, which further confirms the role of these enzymes in DOX cardiotoxicity. Furthermore, gene expression of P450 and sEH was altered in an organ-specific manner. As a result, the chronic DOX administration leads to an imbalance between P450-mediated cardiotoxic and cardioprotective pathways. Therefore, P450 ω-hydroxylases and sEH might be considered as novel targets to prevent and/or treat DOX cardiotoxicity.

Topics: Animals; Apoptosis; Arachidonic Acid; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Hypertrophic; Cells, Cultured; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System; Doxorubicin; Epoxide Hydrolases; Gene Expression; Heart; Inflammation; Kidney; Liver; Male; Microsomes; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger

Growth differentiation factor 15 (GDF15), ST2, high-sensitivity troponin T (hsTnT), and N-terminal pro brain natriuretic peptide (NT-proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT-proBNP)].. We compared circulating levels of GDF15, ST2, hsTnT, and NT-proBNP, as well as their combinations, in compensated patients with clinical HF with reduced ejection fraction (HFREF) (n = 51), HF with preserved ejection fraction (HFPEF) (n= 50), and community-based controls (n = 50). Compared with controls, patients with HFPEF and HFREF had higher median levels of GDF15 (540 pg/mL vs. 2529 and 2672 pg/mL, respectively), hsTnT (3.7 pg/mL vs. 23.7 and 35.6 pg/mL), and NT-proBNP (69 pg/mL vs. 942 and 2562 pg/mL), but not ST2 (27.6 ng/mL vs. 31.5 and 35.3 ng/mL), adjusting for clinical covariates. In receiver operating characteristic curve analyses, NT-proBNP distinguished HFREF from controls with an area under the curve (AUC) of 0.987 (P < 0.001); GDF15 distinguished HFPEF from controls with an AUC of 0.936 (P < 0.001); and the combination of NT-proBNP and GDF15 distinguished HFPEF from controls with an AUC of 0.956 (P < 0.001). NT-proBNP and hsTnT levels were higher in HFREF than in HFPEF (adjusted P < 0.04). The NT-proBNP:GDF15 ratio distinguished between HFPEF and HFREF with the largest AUC (0.709; P < 0.001).. Our study provides comparative data on physiologically distinct circulating biomarkers in HFPEF, HFREF, and controls from the same community. These data suggest a prominent role for myocardial injury (hsTnT) with increased wall stress (NT-proBNP) in HFREF, and systemic inflammation (GDF15) in HFPEF.

Topics: Area Under Curve; Biomarkers; Case-Control Studies; Echocardiography, Doppler; Electrocardiography; Female; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments; Prospective Studies; Receptors, Cell Surface; ROC Curve; Singapore; Stroke Volume; Troponin T; Ventricular Remodeling

The aim of the study was to assess the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with congestive heart failure (CHF) treated with cardiac resynchronization therapy (CRT). 97 patients (age 54.9+/-9.9 years; 87% men) with implanted CRT devices (median period after implantation 19.9+/-19.3 months) were enrolled. According to NT-proBNP level patients were divided into tertiles: first (n=36) - less than 848 pg/ml, second (n=29) - from 848 to 2936 pg/ml, and third (n=32) - more than 2936 pg/ml. We didnt find a relationship between inflammatory mediators, NT-probNP level and time after implantation. In the total group NT-proBNP significantly correlated with structural and functional parameters of the heart. In the first group in comparison with the third group levels of IL-6 were lower (pI-III=0.019) and levels of IL-l - higher (pI-III=0.006). IL-10, CRP, TNF- did not differ between groups. In the first group IL-l straightly correlated with IL-6, TNF- , IL-10 and left ventricular ejection fraction (LVEF), in the third group IL-6 straightly correlated with CRP, while correlation of IL-l with LVEF became negative. We suppose that in patients with mild HF IL-l can play an adaptive role. High levels of IL-6, CRP probably can be used as markers of CHF progression in patients treated with CRT.

Topics: Biomarkers; Cardiac Resynchronization Therapy Devices; Cytokines; Female; Follow-Up Studies; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Severity of Illness Index; Ventricular Function, Left

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

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

B-type natriuretic peptide (BNP) and inflammatory markers are implicated in the pathophysiology of both ischemic cardiomyopathy and complications after cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to assess preoperative and postoperative levels of BNP, interleukin-6 (IL-6), interleukin-8 (IL-8), P-selectin, intercellular adhesion molecule (ICAM), C-reactive protein (CRP) in patients undergoing cardiac surgery with CPB and investigate their variation and ability to correlate with immediate outcome.. Plasma levels of these markers were measured preoperatively, 6 and 24 h after CBP in 62 patients. Main endpoints were requirements for intra-aortic balloon pump, intensive care unit (ICU) stay longer than five days, ventilator dependence >24 h, requirement for dobutamine, hospital stay >10 days, clinical complications (infection, myocardial infarction, renal failure, stroke and ventricular arrhythmias) and in-hospital mortality.. Preoperative BNP levels correlate with longer ICU stay (P = 0.003), longer ventilator use (P = 0.018) and duration of dobutamine use (P < 0.001). The receiver-operating characteristic curve demonstrated BNP levels >190 pg/ml as predictor of ICU >5 days and BNP levels >20.5 pg/ml correlated with dobutamine use, with areas under the curve of 0.712 and 0.842, respectively. Preoperative levels of ICAM-1 were associated with in-hospital mortality (P = 0.042). In the postoperative period, was found association between CRP, IL-6 and P-selectin with ventilation duration (P = 0.013, P = 0.006, P < 0.001, respectively) and P-selectin with ICU stay (P = 0.009).. BNP correlates with clinical endpoints more than inflammatory markers and can be used as a predictor of early outcome after heart surgery.

Topics: Acrylamides; Aged; beta-Alanine; Biomarkers; Brazil; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cardiotonic Agents; Chi-Square Distribution; Dobutamine; Female; Hospital Mortality; Humans; Inflammation; Inflammation Mediators; Intensive Care Units; Interleukin-6; Interleukin-8; Intra-Aortic Balloon Pumping; Length of Stay; Male; Middle Aged; Natriuretic Peptide, Brain; P-Selectin; Postoperative Complications; Respiration, Artificial; Risk Assessment; Risk Factors; ROC Curve; Time Factors; Treatment Outcome

Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed.. Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n = 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (β = 0.39, P < 0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (β = 0.26, P < 0.0001) and IL-10 (β = 0.15, P < 0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2-2.9, P = 0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP.. Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart--kidney interactions.

Topics: Biomarkers; Cystatin C; Heart Failure; Humans; Inflammation; Interleukin-6; Kidney Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Syndrome; Tumor Necrosis Factor-alpha

Free fatty acids (FFAs) are the major energy sources of the heart, and fatty acids (FAs) are active components of biological membranes. Data indicate that levels of FAs and their composition may influence myocardial function and inflammation. The aim of this study was to investigate whether total levels and composition of FAs and FFAs in plasma are altered in clinical heart failure (HF) and whether any alterations in these parameters are correlated with the severity of HF.. Plasma from 183 patients with stable HF was compared with plasma from 44 healthy control subjects.. Our main findings are as follows: (i) patients with HF had decreased levels of several lipid parameters and increased levels of FFAs in plasma, compared with controls, which were significantly correlated with clinical disease severity. (ii) Patients with HF also had a decreased proportion in the plasma of several n-3 polyunsaturated FAs, an increased proportion of several monounsaturated FAs, and a decreased proportion of some readily oxidized long-chain saturated FAs. (iii) These changes in FA composition were significantly associated with functional class, impaired cardiac function (i.e., decreased cardiac index and increased plasma N-terminal pro-B-type natriuretic peptide levels) and enhanced systemic inflammation (i.e., increased high-sensitivity C-reactive protein levels). (iv) Low levels of C20:4n-3 (eicosatetraenoic acid) and in particular high levels of C18:1n-7 (vaccenic acid) were significantly associated with total mortality in this HF population.. Our data demonstrate that patients with HF are characterized by a certain FA phenotype and may support a link between disturbed FA composition and the progression of HF.

Topics: Adult; Aged; Arachidonic Acids; Biomarkers; C-Reactive Protein; Chronic Disease; Confounding Factors, Epidemiologic; Disease Progression; Fatty Acids, Unsaturated; Female; Heart Failure; Humans; Inflammation; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Oleic Acids; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index

Depressive symptoms in patients with heart failure (HF) are common and might be associated with inflammation. No studies have examined both the cross-sectional and prospective association between inflammation and depressive symptoms in patients with HF with adequate correction for disease severity. The aim of this study was to describe if the cytokines interleukin-6 (IL-6) and C-reactive protein (CRP) are associated with depressive symptoms in hospitalized HF patients.. Data from 517 patients hospitalized for HF from the COACH study were analyzed on inflammation markers (IL-6 and CRP) and depressive symptoms (Center for Epidemiological Studies Depression-Scale).. Heart failure patients with depressive symptoms (n = 208, 40%) had significantly higher plasma values of IL-6 (median 12.8 pg/mL vs median 11.0 pg/mL, P = .018) and CRP (median 2.4 mg/mL vs median 2.1 mg/mL, P = .03) compared with the nondepressed patients. Structural equation modelling showed that the factor inflammation (including IL-6 and CRP) was associated with depressive symptoms (β = 0.18, P < .05) when left ventricular ejection fraction and plasma values brain natriuretic peptides were included in the model. A small negative (β = -0.18, P < .05) effect was found between inflammation at baseline and the change in depressive symptoms during the 18 months of follow-up.. Higher levels of inflammatory markers are independently associated with depressive symptoms in HF patients, even after correcting for disease severity. There is no clear relationship between inflammation at baseline and depressive symptoms during the 18 months of follow-up.

Topics: Aged; C-Reactive Protein; Depression; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume

Chronic pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) and fibrosing lung diseases, and atrial fibrillation (AF), are prevalent in elderly people. The impact of cardiac co-morbidities in the elderly, where pulmonary function is impaired, cannot be ignored as they influence mortality. The relationship between the prevalence of AF and pulmonary function is unclear. The aim of this study was to evaluate this relationship in participants in a health check.. Subjects aged 40 or older (n = 2,917) who participated in a community-based annual health check in Takahata, Japan, from 2004 through to 2005, were enrolled in the study. We performed blood pressure measurements, blood sampling, electrocardiograms, and spirometry on these subjects.. The mean FEV(1) % predicted and FVC % predicted in AF subjects was significantly lower than in non-AF subjects. The prevalence of AF was higher in those subjects with airflow limitation or lung restriction than in those without. Furthermore, AF prevalence was higher in those subjects with severe airflow obstruction (FEV(1) %predicted < 50) than in those who had mild or moderate airflow obstruction (FEV(1) %predicted ≥ 50), although there was no difference between the prevalence of AF in subjects with 70≤ FVC %predicted <80 lung restriction and those with FVC %predicted <70. Multiple logistic regression analysis revealed that FEV(1) %predicted and FVC %predicted are independent risk factors for AF (independent of age, gender, left ventricular hypertrophy, and serum levels of B-type natriuretic peptide).. Impaired pulmonary function is an independent risk factor for AF in the Japanese general population.

Topics: Adult; Aged; Airway Obstruction; Atrial Fibrillation; C-Reactive Protein; Electrocardiography; Female; Forced Expiratory Volume; Humans; Hypertension; Inflammation; Japan; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prevalence; Risk Factors; Smoking; Spirometry; Vital Capacity

Cardiomyocyte stretching has been reported to be a major trigger for brain natriuretic peptide (BNP) release; however, an increase in circulating BNP is observed in patients with acute myocardial ischemia in the absence of increased left ventricular wall stress or cardiomyocyte stretching. In the present study, to investigate the direct and independent effects of acute myocardial ischemia on BNP expression and its mechanism, we established an in vitro glucose-free ischemia and hypoxia injured model of cultured rat cardiomyotes and proved hypoxia upregulated expressions of interleukin-6(il-6) and BNP. Further treatment with il-6 elicited dose- and time-dependent increases in BNP mRNA and protein expression as well as an upregulation in transforming growth factor-β1 (TGF-β1)/Smad2 expression, which was partially suppressed by a neutralizing antibody. In conclusion, our study showed that acute myocardial ischemia can directly upregulate BNP expression at the translational and transcriptional levels through the action of il-6, and this process is associated with the upregulation of TGF-β1/Smad2 signal path.

Topics: Animals; Antibodies, Neutralizing; Cell Survival; Cytokines; Gene Expression Regulation; Hypoxia; Inflammation; Inflammation Mediators; Interleukin-6; Myocardial Ischemia; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Smad2 Protein; Transcription, Genetic; Transforming Growth Factor beta1

Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery.. We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 wk) and late (> 6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients.. ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF.

Topics: Adipokines; Adiponectin; Analysis of Variance; Body Mass Index; Chronic Disease; Disease Progression; Female; Heart Failure; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Resistin; Tumor Necrosis Factor-alpha

The levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were investigated to analyze the systemic inflammation in chronic obstructive pulmonary disease (COPD) patients with and without pulmonary hypertension.. From January 2006 to December 2010, 89 patients with COPD were enrolled in our hospital. There were 67 males and 22 females, with a mean age of (70 ± 7) and a mean FEV(1) of (47 ± 13)%. Pulmonary pressure was assessed by Doppler echocardiography. The levels of plasma BNP, TNF-α and ET-1 were measured by enzyme-linked immunosorbent assay kits. High-sensitivity plasma CRP level was assessed by chemiluminescent immunoassay.. Forty-two patients were classified as COPD with pulmonary hypertension group and 47 patients as COPD without pulmonary hypertension group. The level of CRP [51.4 mg/L (20.1 - 92.0) mg/L], ET-1 [5.9 ng/L (3.7 - 10.4) ng/L] and BNP [303.2 ng/L (112.5 - 824.7) ng/L] in patients with pulmonary hypertension were significantly higher than in that in patients without hypertension, CRP [26.7 mg/L (11.5 - 62.9) mg/L], ET-1 [2.1 ng/L (1.3 - 4.7) ng/L] and BNP [143.7 ng/L (85.5 - 306.7) ng/L]. The level of TNF-α showed no difference between the 2 groups [8.5 ng/L (4.8 - 13.7) ng/L and 6.7 ng/L (3.2 - 10.3) ng/L], respectively. Multivariate analysis showed that PaO₂ (P < 0.05), CRP (P < 0.05) and BNP (P < 0.05) could predict pulmonary hypertension independently.. The level of CRP, ET-1 and BNP were related to pulmonary hypertension in COPD patients, suggesting that systemic inflammation play a role in the pathogenesis of pulmonary hypertension in COPD.

Topics: Aged; C-Reactive Protein; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Inflammation, overhydration and elevated cardiac biomarkers are related to outcome in haemodialysis (HD) patients. Here, we explored the relationship between the body composition (BC), inflammation and cardiac biomarker concentrations in HD patients longitudinally.. A total of 44 HD patients were followed for 6 months. BC was assessed by multifrequency bioimpedance (BIA). Serum concentrations of cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were assessed at 2 monthly intervals. The longitudinal data analysis was conducted with a marginal model.. During the follow-up, the parameters describing the BC were highly predictive of both BNP and NT-proBNP and independent of gender, time, hsCRP and cTnT concentrations. The intracellular water (ICW)/body weight (BW) ratio (reflecting malnutrition) exerted a negative effect, whereas the extracellular water (ECW)/BW ratio (reflecting overhydration) had a positive effect on BNP and NT-proBNP concentrations. HsCRP and cTnT concentrations were significantly associated with each other. Furthermore, NT-proBNP concentrations were predictive of cTnT and hsCRP concentrations.. In the present study, we find a significant relation between BIA-derived BC parameters and natriuretic peptide concentrations. This relationship was independent of the cardiac history of the patient and suggests that the natriuretic peptide levels are to some degree modifiable by changing a patient's fluid distribution. Moreover, cTnT, BNP, NT-proBNP and hsCRP were significantly related, showing a complex relation between overhydration, malnutrition, inflammation and cardiac biomarkers in dialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Composition; Body Fluids; C-Reactive Protein; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Inflammation; Kidney Failure, Chronic; Longitudinal Studies; Male; Malnutrition; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Regression Analysis; Renal Dialysis; Troponin T

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 aim of this study was to determine the role of the N-terminal prohormone form of BNP (NT-proBNP) in patients with acute community-acquired infection as a predictive marker and its correlation with the type of infection. We studied 42 patients with acute community-acquired infection. Levels of NT-proBNP were measured in all patients at hospital admission and on the third day, as well as in a control group of 84 healthy blood donors. NT-proBNP levels were markedly elevated in patients, 5897 versus 108 pg/ml in the control group (P=0.01) A positive association between the NT-proBNP levels and the final outcome of infection (P<0.0001) was found. Multivariate regression analysis identified NT-proBNP levels as the most important predictor of unfavorable outcome (P=0.017). Patients with lower respiratory tract infection had the maximum increase in NT-proBNP levels (P<0.048) and the most unfavorable outcome (P<0.03) regarding other sites of infection.

Topics: Biomarkers; Community-Acquired Infections; Cytokines; Female; Greece; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Regression Analysis; ROC Curve; Sensitivity and Specificity; Statistics as Topic

Atrial fibrillation (AF) is associated with a high risk of stroke. The contribution of arrhythmia to events is clear in sustained forms of AF, but in paroxysmal AF, presently available data have yet to identify what proportion of time spent in AF (ie, arrhythmia burden [AFB]) is of clinical relevance. We aimed to assess this relationship using surrogate blood markers for the hypercoagulable state associated with AF.. One hundred twenty-one consecutive outpatients (mean age 74.7 +/- 7.8 years; 73 [60.3%] men) with pacemakers capable of arrhythmia detection were recruited. AFB was assessed over a 1-month period and classified as AFB = 0%, 0.1% to 10%, 10.1% to 50%, or > 50%.. Baseline characteristics and comorbidities were comparable between groups. There were no significant differences in levels of soluble E-selectin (sE-selectin), von Willebrand factor (vWf), high-sensitivity C-reactive protein, interleukin-6, soluble P-selectin (sP-selectin), or tissue factor (TF) across the four patient groups. Levels of plasma brain natriuretic peptide (BNP) were approximately twofold greater in the group with the highest AFB (P < .001). Following a stepwise multiple linear regression analysis, age was a significant predictor of vWf (P = .010), sP-selectin (P = .042), and BNP (P = .012). Left ventricular fractional shortening was predictive of BNP (P = .001) and sE-selectin (P = .012). Anticoagulation was a predictor of vWf levels (P = .005), and hypertension was predictive of TF (P < .001).. Given no appreciable difference in levels of prothrombotic markers in relation to AFB in this study, it is plausible that these abnormalities do, in fact, relate to underlying risk factors, and that such patients should be anticoagulated if risk factors dictate. Thus, AFB per se should probably not influence the decision to anticoagulate, but rather the presence of AF combined with clinical risk scoring should remain the predominant tool for stroke risk assessment.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Cohort Studies; Cross-Sectional Studies; E-Selectin; Female; Humans; Inflammation; Interleukin-6; Linear Models; Male; Natriuretic Peptide, Brain; P-Selectin; Pacemaker, Artificial; Risk Assessment; Risk Factors; Stroke; Thrombosis; von Willebrand Factor

N-terminal pro-B-type natriuretic peptide (NT-pro BNP), a biomarker of heart failure, is involved in regulation of the body fluid homeostasis and vascular tone. The purpose of this study was to investigate the relationship between serum level of NT-pro BNP and nutritional status, inflammation and hydration in patients on maintenance hemodialysis (HD).. The study involved 97 HD patients (mean age: 65.3 +/- 13.9 years, HD duration: 36.3 +/- 43.5 months). Blood tests comprised the measurements of serum levels of NT-pro BNP, interleukin-6 (IL-6), human soluble tumor necrosis factor receptor I (s TNF RI), hemoglobin (Hb), albumin (alb) and urea. Furthermore, normalized protein catabolic rate (n PCR), body mass index (BMI), mean arterial blood pressure (MAP), adequacy of HD (Kt/V), and interdialytic body weight gain (IBWG) were calculated. In addition, NT-pro BNP was measured in a healthy control group (CG; n = 24, mean age 49.5 +/- 15.0 years). Hydration status was determined by bioimpedance analysis (BIA).. Irrespective of gender, NT-pro BNP levels were markedly elevated in HD patients compared with CG (15879.2 +/- 14033.3 pg/ml vs. 73.45 +/- 23.56 pg/ml; p < 0.00001). NT-pro BNP was unrelated to any measures of body fluid compartments. Multivariate regression analysis revealed that only four parameters (nPCR, Hb, MAP, and total time on HD) influenced serum NT-pro BNP levels.. While there was only moderate direct association of NT-pro BNP with hydration status, it was elevated in patients with intensive catabolism, severe anemia, higher MAP and longer total duration of HD.

Topics: Aged; Body Water; Female; Glycoproteins; Hemoglobins; Homeostasis; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nutritional Status; Peptide Fragments; Receptors, Tumor Necrosis Factor, Type I; Regression Analysis; Renal Dialysis; Serum Albumin; Serum Albumin, Human; Sex Factors; Spectrum Analysis

Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial.. In 3120 Framingham cohort participants (mean age 58.4+/-9.7 years, 54% women), we related 10 biomarkers that represented inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B-type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide), oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen activator inhibitor type 1), and microvascular damage (urinary albumin excretion; n=2673) to incident AF (n=209, 40% women) over a median follow-up of 9.7 years (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker panel was associated with incident AF (P<0.0001). In stepwise-selection models (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62, 95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard ratio 1.25, 95% confidence interval 1.07 to 1.45, P=0.004) were chosen. The addition of BNP to variables recently combined in a risk score for AF increased the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95% confidence interval 0.78 to 0.83) and showed an integrated discrimination improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9% relative improvement in reclassification analysis. The combined analysis of BNP and C-reactive protein did not appreciably improve risk prediction over the model that incorporated BNP in addition to the risk factors.. BNP is a predictor of incident AF and improves risk stratification based on well-established clinical risk factors. Whether knowledge of BNP concentrations may be used to target individuals at risk of AF for more intensive monitoring or primary prevention requires further investigation.

Topics: Aged; Atrial Fibrillation; Biomarkers; Female; Follow-Up Studies; Humans; Incidence; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Residence Characteristics; Signal Transduction

Topics: Biomarkers; C-Reactive Protein; Heart Diseases; Humans; Hypertension, Pulmonary; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive

Plasma BNP and NT-proBNP are often regarded as interchangeable parameters in assessing heart failure (HF) severity and prognosis. Renal failure results in disproportionate increases of NT-proBNP and an increased NT-proBNP/BNP ratio. Low kidney function is therefore considered particularly when NT-proBNP is used to assess HF. The purpose of this study was to identify other conditions affecting the NT-proBNP/BNP ratio. We examined the NT-proBNP/BNP ratio, 26 other lab parameters, and clinical factors in 218 patients admitted to the HF ward. In addition to renal function, we also found significant correlations between the NT-proBNP/BNP ratio and inflammation as measured by orosomucoid (r = 0.525, p < 0.0001), CRP (r = 0.333, p < 0.0001), haptoglobulin (r = 0.201, p = 0.02), and alpha1-antitrypsin (r = 0.223, p = 0.01). Reverse correlation was found with transferrin (r = -0.323, p < 0.0001), albumin (r = -0.251, p = 0.003), and S-Fe (r = -0.205, p = 0.02), parameters known to decrease during inflammation. Inflammation increased levels of NT-proBNP more than BNP, resulting in an increased NT-proBNP/BNP ratio. Our findings indicate that NT-proBNP should be evaluated concomitantly with inflammatory status to avoid overestimation of HF severity.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Glomerular Filtration Rate; Heart Failure; Humans; Inflammation; Kidney Function Tests; Male; Mathematical Computing; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Retrospective Studies; Severity of Illness Index

Acute kidney injury (AKI) after myocardial infarction is associated with poor clinical outcome. However, mechanisms of the adverse effect of AKI on clinical outcome after reperfused ST-elevation myocardial infarction (STEMI) have not been fully elucidated.. We examined 141 consecutive patients with reperfused first anterior STEMI. AKI was defined as an increase in serum creatinine of >or=0.3mg/dL within 48hours after admission. Patients with AKI had higher incidence of in-hospital cardiac death (P=.0004) and major adverse cardiac events (MACE, P=.020) during a mean of 39+/-40 (range, 1 to 96) months than those without, in association with adverse left ventricular (LV) remodeling. White blood cell count on admission and peak C-reactive protein were higher in patients with than those without AKI. Plasma norepinephrine on admission, interleukin-6, brain natriuretic peptide, and malondialdehyde-modified low-density lipoprotein 2 weeks after STEMI were higher in patients with AKI than those without AKI. Cox proportional hazards model analysis revealed AKI was an independent predictor of MACE (hazard ratio=2.38, P=.019).. AKI was a strong predictor of MACE in association with adverse LV remodeling. Enhanced inflammatory response, oxidative stress, and neurohormonal activation may synergistically accelerate renal dysfunction and LV remodeling after STEMI.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Cholesterol, LDL; Creatinine; Female; Heart Failure; Heart Ventricles; Humans; Incidence; Inflammation; Interleukin-6; Japan; Logistic Models; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Natriuretic Peptide, Brain; Norepinephrine; Oxidative Stress; Prognosis; Proportional Hazards Models; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling

Left ventricle remodeling (LVR) is a relatively common and unfavourable event occurring after acute myocardial infarction. A link exists between inflammation and LVR. Neopterin, a marker of inflammation and macrophage activation, is a predictor of left ventricular dysfunction in patients with coronary artery disease. We therefore sought to assess whether both neopterin and brain natriuretic peptide (BNP), a marker of LV dysfunction and patient outcome, correlate with LVR in patients with ST-segment elevation myocardial infarction (STEMI).. We prospectively assessed 108 STEMI patients (age 64 + or - 11 years; 85% male) undergoing primary percutaneous coronary intervention (PCI) who were assessed echocardiographycally assessment was performed at 96 + or - 10h after the onset of symptoms and 12 month after STEMI. LVR was defined as >20% increase in LV end-diastolic volume at 12 months of follow-up compared to baseline. Neopterin and BNP serum concentrations were measured immediately before primary PCI.. At 1 year, 21 patients (19%) showed LVR and 87 (81%) had no LVR. Patients with LVR had higher levels of neopterin at study entry (7.45 + or - 1.04 vs 5.19 + or - 1.39 nmol/L; p<0.001). After adjustment for relevant confounders, neopterin levels were found to be an independent predictor of LVR (OR ranging from [3.10, CI 95% 1.928-4.990, p<0.001] to [3.32, CI 95% 1.999-5.532, p<0.001]). ROC analysis showed an area under the curve of 0.901 for neopterin (CI 95% 0.84-0.96, p<0.0001) compared to 0.579 for BNP (CI 95% 0.409-0.748) regarding LVR.. In STEMI patients undergoing primary PCI, high neopterin levels - but not BNP - predict LVR at 1-year follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Echocardiography; Female; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Neopterin; Regression Analysis; Risk Factors; ROC Curve; Ventricular Remodeling

We compared the 1-year predictive value of several inflammatory and non-inflammatory biomarkers in ACS patients.. In 610 patients (73.0% male)--36.0% unstable angina (UA) and 64.0% NSTEMI--we assessed high-sensitivity C-reactive protein (hs-CRP), interleukins 6, 10 and 18, soluble CD40 ligand, P- and E-selectin, NT-proBNP, fibrinogen and cystatin C at hospital admission. Two outcomes at 1-year follow up were selected for analysis: (1) all-cause death, MI, UA, or coronary revascularization, and (2) all-cause death, and non-fatal MI. The effect of biomarker levels on endpoints was examined by the Cox proportional hazards model, and their discrimination ability with the C statistic (AUC).. Of 549 patients (90.0%) who completed the 1-year follow up, 206 (37.5%) and 54 (8.9%) reached the first and second composite endpoints, respectively. None of the biomarkers studied improved prediction of the first endpoint. However, considered as continuous variables, and in combination, NT-proBNP and fibrinogen, increased the AUC from 0.64 (95% CI 0.55-0.72) to 0.73 (95% CI 0.64-0.81; p=0.02) for prediction of the second endpoint. Cut-off values for NT-proBNP and fibrinogen, regarding best sensitivity and specificity for prediction of the secondary endpoint were 1043.9 ng/L and 4.47 mg/dL, respectively. For these cut-off points, sensitivity, specificity, positive predictive value and negative predictive value were 40.5% vs 59.5%, 83.3% vs 67.1%, 18.8% vs 14.9% and 93.5% vs 94.4% for NT-proBNP and fibrinogen, respectively.. In ACS patients, inflammatory biomarkers offer modest incremental information to that provided by clinical risk markers. Fibrinogen and NT-proBNP measurements, however, improve cardiovascular risk prediction.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Area Under Curve; Biomarkers; Cardiovascular Diseases; Female; Humans; Inflammation; Macrophages; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Proportional Hazards Models; Protein Structure, Tertiary; T-Lymphocytes; Time Factors

B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freund's adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+-activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory effects on formalin-induced flinching behavior and CFA-induced thermal hyperalgesia in rats. Blockade of BNP signaling by BNP antibodies or cGMP-dependent protein kinase (PKG) inhibitor KT5823 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester] impaired the recovery from CFA-induced thermal hyperalgesia. Thus, BNP negatively regulates nociceptive transmission through presynaptic receptor NPR-A, and activation of the BNP/NPR-A/PKG/BKCa channel pathway in nociceptive afferent neurons could be a potential strategy for inflammatory pain therapy.

Topics: Analysis of Variance; Animals; Antibodies; Biophysical Phenomena; Calcitonin Gene-Related Peptide; Carbazoles; Disease Models, Animal; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Excitatory Postsynaptic Potentials; Freund's Adjuvant; Ganglia, Spinal; Gene Expression Regulation; Glutamic Acid; Hyperalgesia; Inflammation; Lectins; Male; Membrane Potentials; Natriuretic Peptide, Brain; Pain; Pain Measurement; Patch-Clamp Techniques; Peptides; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Sensory Receptor Cells; Signal Transduction; Time Factors

Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.. We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048).. Serum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.

Topics: Adipokines; Aged; Biomarkers; Case-Control Studies; Chitinase-3-Like Protein 1; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Glomerular Filtration Rate; Glycoproteins; Heart Atria; Heart Failure; Hospitalization; Humans; Hypertension; Inflammation; Lectins; Male; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Severity of Illness Index; Sodium; Uric Acid

Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.. 243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.. 20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI.

Topics: Adipokines; Aged; Biomarkers; Chitinase-3-Like Protein 1; Coronary Artery Disease; Female; Glycoproteins; Humans; Inflammation; Interleukin-6; Ischemia; Lectins; Male; Middle Aged; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk; Sex Factors

Increased levels of TNF-alpha, IL-6, their soluble receptors, and NT-proBNP have been observed in patients with dilated cardiomyopathy (DCM). In the present study, we assessed the possible involvement of proinflammatory cytokines and their soluble receptors with and without recovery of LV function in DCM patients.. Forty patients with DCM were enrolled and divided into two groups: Group I consisted of DCM patients (n = 30) whose left ventricular ejection fraction (LVEF) had not recovered on follow up and Group II comprised DCM patients (n = 10) whose LVEF had recovered. Ten healthy subjects were included as controls (Group III). TNF-alpha, IL-6,TNFR1, TNFRII, gp130, and NT-proBNP levels were significantly increased in Group I and were significantly lower in patients with LVEF recovery as compared to those without recovery of LVEF (P < 0.05).. Circulating TNF-alpha, IL-6, and NT-proBNP appear to correlate with the LV function recovery of patients with DCM and could be used as prognostic biomarkers.

Topics: Adult; Biomarkers; Cardiomyopathy, Dilated; Case-Control Studies; Cytokine Receptor gp130; Cytokines; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Young Adult

Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients.. Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than those with KCCQ-s>or=50. Worse health status was also associated with shorter event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ-s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002-0.824, P=0.037) were independent predictors of event-free survival at 250 days.. KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.

Topics: Attitude to Health; Biomarkers; Chronic Disease; Depression; Disease-Free Survival; Female; Health Status; Heart Failure; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Quality of Life; Surveys and Questionnaires; Walking

Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for ischaemic heart disease, independent of smoking history, and inflammation is thought to play a role.. We sought to ascertain whether occult myocardial infarction (MI) was present in the COPD population, and to assess its relationship with inflammation and natriuretic peptides.. We recruited 25 patients with moderate/severe COPD and 17 control smokers without lung disease. All participants had no known cardiac disease. Contrast-enhanced cardiac magnetic resonance imaging was performed and analysed for delayed contrast enhancement (DE), indicative of previous MI. All participants had venous blood samples taken for assessment of NT-proBNP and inflammatory markers.. DE was not found in any participant. Right ventricular ejection fraction was lower in COPD patients. Other cardiac measurements and NT-proBNP levels were similar in the 2 groups. C-reactive protein, IL-8, GM-CSF, IL-1 beta and TNF-alpha were all significantly higher in the COPD group.. DE, indicating previous MI, was not found in patients with moderate/severe COPD. Occult MI does not appear to be common in this population, but a larger study would be needed to conclusively test this.

Topics: Aged; Biomarkers; Cross-Sectional Studies; Female; Gadolinium DTPA; Humans; Inflammation; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Smoking

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

Hyperhomocysteinemia, neurohormonal activation, inflammation and altered fibrinolysis have been linked to atherothrombosis as well as to myocardial fibrosis and heart failure. Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample.. We related nine biomarkers representing select biologic pathways (independent variables: C-reactive protein, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and homocysteine) to three plasma markers of collagen turnover [dependent variables, separate models for each: aminoterminal propeptide of type III collagen, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-9 (present versus absent)] in 921 Framingham Heart study participants (mean age 57 years; 58% women). Participants were separated a priori into those with left ventricular end-diastolic dimensions and wall thickness below sex-specific median values (referent group) and either measure at least 90th sex-specific percentile ('remodeled' group). We used stepwise multivariable regression analysis adjusting for cardiovascular risk factors to relate the panel of systemic biomarkers to the three biomarkers of collagen metabolism.. Plasma homocysteine was positively related to all three markers of collagen metabolism in the remodeled group and to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in the referent group. Plasminogen activator inhibitor-1 was positively related to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in both groups, whereas the natriuretic peptides were associated positively with these collagen markers in the referent group.. In our large community-based sample, plasma homocysteine and plasminogen activator inhibitor-1 were positively related to circulating collagen biomarkers, consistent with experimental studies implicating these pathways in cardiovascular collagen turnover.

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Collagen; Collagen Type III; Cross-Sectional Studies; Data Collection; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Homocysteine; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Plasminogen Activator Inhibitor 1; Protein Precursors; Renin; Renin-Angiotensin System; Tissue Inhibitor of Metalloproteinase-1; Ventricular Remodeling

The roles of metabolic syndrome and chronic subclinical inflammation in arterial stiffening and the development of heart failure remain to be elucidated. Whether adiponectin and high-sensitivity C-reactive protein (hs-CRP) were independently related to brachial-ankle pulse-wave velocity (ba-PWV) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in the general population were investigated. Eligible study subjects were 445 Chinese residents aged > or =40 years who participated in a community-based survey, underwent examination of ba-PWV, and had complete data of serum adiponectin, hs-CRP (<10 mg/L), and NT-pro-BNP. Adiponectin, but not hs-CRP, was independently related to ba-PWV (standardized regression parameter -0.107, p <0.05) when age, gender, body mass index, and number of metabolic syndrome components were accounted for. On the other hand, ba-PWV, adiponectin, and hs-CRP were independently related to NT-pro-BNP (standardized regression parameters 0.116, 0.188, and 0.094, respectively; all p <0.05) when age, gender, body mass index, number of metabolic syndrome components, and renal function were accounted for. In conclusion, adiponectin, but not hs-CRP, is independently associated with both ba-PWV and NT-pro-BNP in the general population. Because adiponectin, hs-CRP, ba-PWV, and NT-pro-BNP may represent markers for metabolic syndrome, chronic subclinical inflammation, arterial stiffness, and ventricular dysfunction, respectively, our results suggest that adiponectin may directly modulate both arterial stiffening and ventricular dysfunction. In contrast, hs-CRP may independently contribute to ventricular dysfunction, but not arterial stiffening.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Anthropometry; Biomarkers; Blood Flow Velocity; C-Reactive Protein; Cardiovascular Diseases; China; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulse; Radioimmunoassay; Risk Assessment; Risk Factors; Surveys and Questionnaires

Emerging evidence indicates the prognostic importance of cystatin C (Cys-C) in patients with coronary artery disease. However, whether Cys-C concentrations are associated with adverse clinical events among patients with acute coronary syndromes (ACS) have not been studied extensively. We compared the long-term prognostic efficacy of Cys-C with other markers of renal dysfunction, inflammation and systolic dysfunction in patients with ACS.. Serum levels of Cys-C, high sensitive C-reactive protein (hs-CRP), brain natriuretic peptide (BNP) and creatinine were measured in 160 patients with ACS (112 males, 48 females, mean age 60+/-10 years) on admission. Primary end point of the study was major adverse cardiac events (MACE) defined as the combination of cardiac death, non-fatal myocardial infarction and recurrent rest angina that required hospitalization within 12 months of follow-up. During the follow-up period, 42 (26%) patients met the MACE criteria. The occurrence of MACE was significantly higher among patients with higher Cys-C levels. In multivariate analysis, Cys-C was the most important parameter associated with the occurrence of MACE (OR=9.62, 95% CI=2.3-40.5, p<0.001). ROC curve analysis showed that the predictive cut-off value of Cys-C for MACE was 1051ng/ml. In the Cox regression analysis adjusted for multiple risk factors, Cys-C was found as the most powerful predictor for MACE (RR=9.43, 95% CI=4.0-21.8, p<0.001).. The results of the present study indicate that admission levels of Cys-C may be a good prognostic indicator of recurrent cardiovascular events in patients with ACS. Further studies are needed to confirm these results.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Cystatin C; Female; Humans; Inflammation; Inflammation Mediators; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; ROC Curve; Systole; Time Factors; Ventricular Dysfunction, Left

Our objective was to study the effect of the genetic background on the wound healing process after myocardial infarction (MI) in mice.. MI was induced in five different mouse strains (BalbC, C57Bl6, FVB, 129S6, and Swiss). At 3, 14, and 28 days after MI, cardiac dimensions were monitored by echocardiography and histology, whereas cardiac function was determined by direct intraventricular pressure measurements (dP/dt). Furthermore, matrix metalloproteinases were measured by zymography, and mRNA expression by quantitative PCR. Infarct rupture, which typically occurred at 3-6 days post-MI, was most frequent in 129S6 mice (62%), followed by C57Bl6 (36%), FVB (29%), Swiss (23%), and BalbC (5%). The high incidence of infarct rupture in 129S6 mice was associated with high systolic blood pressure and increased influx of inflammatory cells. Cardiac dilatation was most marked in Swiss mice and least prominent in 129S6 mice. The degree of dilatation was associated with a reduced ejection fraction and decreased dP/dt values at 14 and 28 days post-MI. At day 14 and 28 post-MI, secondary thinning of the infarct area was marked in BalbC, FVB, and Swiss, but absent in C57Bl6 and 129S6 mice. In the latter two groups, this was paralleled by the highest number of myofibroblasts at day 14 post-MI.. The outcome of infarct healing in mice strongly depends on genetic background. On the basis of our results, we suggest that for studies on infarct rupture, the 129S6 mouse is the background of choice, whereas BalbC and Swiss mice are the preferred models to study infarct thinning post-MI.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Echocardiography; Gene Expression Regulation, Enzymologic; Heart Rupture, Post-Infarction; Inflammation; Male; Matrix Metalloproteinases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Polymerase Chain Reaction; RNA, Messenger; Species Specificity; Stroke Volume; Time Factors; Ventricular Function, Left; Ventricular Pressure; Wound Healing

Despite substantial therapeutic advances, heart failure remains a syndrome associated with high morbidity and mortality. The management of heart failure remains challenging despite the recent different therapeutic advances. The emergence of cardiac biomarkers as increasingly effective clinical tools suggests the potential of a new approach to the management of patients with heart failure. A variety of circulating biomarkers of diagnostic and prognostic utility in heart failure is currently being studies in preclinical, observational and randomized prospective studies. Of the various candidate biomarkers, the greatest wealth of knowledge and clinical experience lies with the B-type naturetic peptides. However, because individual biomarkers may have limited sensitivity and specificity, a multi-marker approach, using combinations of different biomarkers that reflect different aspects of the pathophysiological milieu, would contribute to better risk stratification and optimization of therapy.

Topics: Biomarkers; C-Reactive Protein; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain

Several studies suggest that intense exercise may increase the athlete's thrombotic tendency. Available data on those metabolic alteration are still conflicting and their clinical significance is still worth of interest. The aim of the present study was to investigate if widely used markers of cardiac damage such as NT-proBNP levels are affected by homocysteine concentrations during sustained sport activities.. Seventy-eight competitive, non-professional athletes were enrolled in the study; 70 healthy age matched subjects, recruited from blood donors, served as controls. Besides the general clinical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol, LDH, CPK, NT-proBNP and IL-6.. The percentages of athletes with normal and elevated homocysteine levels resulted 46% and 54%, respectively. Mean NT-proBNP levels were significantly higher in athletes than in controls (1176.66 + or - 442.15 pg/mL versus 450.34 + or - 180.39 pg/mL). No correlation was found between homocysteine and NT-proBNP values.. The previously described "sport related" homocysteine is not related to other markers of cardiovascular stress such as NT-proBNP. Available data suggest that both hyperhomocysteinemia and high NT-proBNP levels in healthy young athletes could be interpreted as markers of metabolic and morphologic adaptation to training rather than a risk factor for cardio-vascular diseases.

Topics: Adult; Biomarkers; Case-Control Studies; Competitive Behavior; Female; Health Status; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-6; Male; Motor Activity; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Sports; Statistics as Topic

The prognostic implications of NT-proBNP measured on admission in patients with the ST-elevation myocardial infarction (STEMI) are not so far well elucidated. The present investigation, performed in 198 STEMI patients submitted to percutaneous coronary intervention (PCI), was aimed at assessing the prognostic value of NT-proBNP measured on admission to Intensive Cardiac Care Unit (ICCU) and its relation with the extension of myocardial infarction (indicated by cardiac biomarkers and ejection fraction) and inflammatory markers (C-reactive protein - CRP, erythrocyte sedimentation rate - ESR, leucocytes, fibrinogen). All patients who died during ICCU stay had increased values of NT-proBNP. Each quartile of NT-proBNP resulted directly correlated with age, heart rate, peak Tn I, admission creatinine serum levels, ESR, fibrinogen, and inversely correlated with ejection fraction. At backward logistic regression analysis, NT-proBNP values showed a significative correlation with peak Tn I (OR 1.013; 95% CI 1.001-1.025; p=0.036), and CRP positive (OR 6.450; 95% CI 1.714-24.272; p=0.006); age was close to reaching statistical significance (OR 1.043; 95% CI 0.999-1.089; p=0.055). At long term-follow-up NT-proBNP lacks any prognostic role in predicting adverse events such as hospitalization for rePCI, re-infarction and heart failure. Kaplan-Meier curves showed that all patients dead at follow-up were in the highest NT-proBNP quartiles.

Topics: Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Biomarkers; Blood Sedimentation; Cardiac Care Facilities; Confidence Intervals; Female; Humans; Inflammation; Intensive Care Units; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment; Risk Factors

Dyspnea is a common emergency department (ED) complaint, and it may be associated with significant mortality risk. We studied 599 dyspneic subjects enrolled in an ED. At 1 year, the role of inflammatory markers (including C-reactive protein [CRP]) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) as independent predictors of mortality was assessed. By 1 year, 91 subjects (15.2%) had died. Among patients who died, the median CRP concentration at admission was significantly higher than in survivors: 47.2 mg/L (449.5 nmol/L; interquartile range [IQR], 10.2-101.9 mg/L [97.1-970.5 nmol/L]) vs 7.25 mg/L (69.5 nmol/L; IQR, 2.2-29.6 mg/L [21.0-281.9 nmol/L]; P < .001). For 1-year mortality, CRP had an area under the receiver operating characteristic curve of 0.76 (95% confidence interval [CI], 0.69-0.80; P < .001). In multivariable analysis, a CRP concentration greater than 14 mg/L was a strong predictor of mortality at 1 year (hazard ratio, 2.47; 95% CI, 1.51-4.02; P < .001). In multivariable models, CRP and NT-proBNP demonstrated independent and additive prognostic value. Among dyspneic patients, CRP levels are significantly associated with mortality at 1 year and show additive value to natriuretic peptide testing for prognosis.

Topics: Aged; Biomarkers; C-Reactive Protein; Dyspnea; Humans; Inflammation; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk

Circulating heat shock protein 70 (Hsp70) is present in the circulation of healthy individuals and in patients with various disorders, including chronic heart failure (CHF). However, the source and routes of release of Hsp70 is only partially characterised in clinical samples.. The purpose of this study was to study the clinical and biological correlates of Hsp70 in a CHF population and, for the first time, to investigate the association of HspA1B (also known as Hsp70-2) +1267 alleles with serum Hsp70 levels.. A total of 167 patients (123 men, 44 women) with <45% left ventricular ejection fraction (LVEF) were enrolled; serum Hsp70 level was determined by enzyme-linked immunosorbent assay and HspA1B +1267 polymorphism by polymerase chain reaction-restriction fragment length polymorphism.. Increased Hsp70 levels were present in patients with severe CHF (NYHA III-IV) as compared to the group of NYHA I-II (p = 0.003). Hsp70 levels correlated with LVEF, NT-proBNP, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, gammaGT (p < 0.05) concentrations in patients with severe CHF, although no correlation was observed between Hsp70 and CRP, TNF-alpha, or IL-6. HspA1B allele G was associated with higher Hsp70 levels (p = 0.001) in patients in NYHA IV class as compared to carriers of allele A.. Serum Hsp70 levels were associated with disease severity in heart failure patients. An interaction with the presence of HspA1B +1267 allele G was observed for Hsp70 concentrations. Hsp70 correlates with markers of heart function and hepatic injury, but not with signs of inflammation.

Topics: Aged; Alleles; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Cytokines; Female; Heart Failure; HSP70 Heat-Shock Proteins; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Single Nucleotide; Severity of Illness Index; Single-Blind Method; Stroke Volume; Tumor Necrosis Factor-alpha; Ultrasonography; Ventricular Dysfunction, Left

Increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation.. In 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated.. NT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated.. NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Biomarkers; Blood Pressure; C-Reactive Protein; Calcinosis; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-1; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Regression Analysis; Severity of Illness Index; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear.. We evaluated 2119 Framingham Offspring Study participants (mean age, 57 years; 57% women) who underwent measurements of biomarkers of inflammation (C-reactive protein), hemostasis (fibrinogen and plasminogen activator inhibitor-1), neurohormonal activation (B-type natriuretic peptide), and renin-angiotensin-aldosterone system (aldosterone and renin modeled as a ratio [ARR]) and echocardiography at a routine examination. LV geometry was defined on the basis of sex-specific distributions of LV mass (LVM) and relative wall thickness (RWT): normal (LVM and RWT <80th percentile), concentric remodeling (LVM <80th percentile but RWT >or=80th percentile), eccentric hypertrophy (LVM >or=80th percentile but RWT <80th percentile), and concentric hypertrophy (LVM and RWT >or=80th percentile). We related the biomarker panel to LV geometry using polytomous logistic regression adjusting for clinical covariates and used backwards elimination to identify a parsimonious set of biomarkers associated with LV geometry. Modeled individually, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, and ARR were related to LV geometry (P<0.01). In multivariable analyses, the biomarker panel was significantly related to altered LV geometry (P<0.0001). On backwards elimination, logARR alone was significantly and positively associated with eccentric (odds ratio per SD increment, 1.20; 95% confidence interval, 1.05 to 1.37) and concentric LV hypertrophy (odds ratio per SD increment, 1.29; 95% confidence interval, 1.06 to 1.58).. Our cross-sectional observations on a large community-based sample identified ARR as a key correlate of concentric and eccentric LV hypertrophy, consistent with a major role for the renin-angiotensin-aldosterone system in LV remodeling.

Topics: Aldosterone; Biomarkers; C-Reactive Protein; Cardiomegaly; Electrocardiography; Female; Fibrin; Heart Ventricles; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Plasminogen Activator Inhibitor 1; Regression Analysis; Renin-Angiotensin System; Ultrasonography; Ventricular Function, Left; Ventricular Remodeling

In this study, we assessed factors associated with cardiovascular risk in patients with sleep apnea-hypopnea syndrome (SAHS) through analysis of plasma concentrations of N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity C-reactive protein (hsCRP). In addition, we analyzed the effect of nasal continuous positive airway pressure (nCPAP) on these markers.. Forty-two patients with SAHS (mild to moderate in 15 cases and severe in 27) were compared with 14 individuals without SAHS. The participants were not receiving drug treatment and they did not have diabetes, hypertension, marked dyslipidemia, or cardiovascular disease, which was ruled out both clinically and by echocardiography and (99m)Tc-tetrofosmin scintigraphy at rest and during exercise. The effects of nCPAP in patients with severe SAHS were analyzed after 6 months of treatment.. Following adjustment for age, body mass index, and smoking habit, the mean concentrations of markers were not significantly higher in patients with severe SAHS than in those with mild-to-moderate SAHS or in control subjects. Nevertheless, in patients with SAHS the main factor influencing NTproBNP concentrations was the percentage of time with a nocturnal arterial oxygen saturation of less then 90% (r=0.37, P=.017). No variables predictive of hsCRP concentration were identified. The concentrations of the markers were reduced by nCPAP, but the differences were not statistically significant.. While nocturnal hypoxemia in SAHS is responsible for variations in the plasma concentration of NTproBNP (as a result of cardiovascular changes), SAHS appears not to be associated with the inflammatory marker hsCRP when patients with heart disease, cardiovascular risk factors, or those receiving pharmacologic treatment are excluded.

Topics: Adult; C-Reactive Protein; Continuous Positive Airway Pressure; Female; Hemodynamics; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Sleep Apnea Syndromes

This study was designed to investigate: 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; and the 3) expression of ST2, membrane-anchored ST2L, and its ligand, interleukin (IL)-33, in myocardium, endothelium, and leukocytes from patients with left ventricular (LV) pressure overload and congestive cardiomyopathy.. Serum levels of ST2 are elevated in heart failure. The relationship of ST2 to hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown.. Serum ST2 (pg/ml; median [25th, 75th percentile]) was measured in patients with LV hypertrophy (aortic stenosis) (n = 45), congestive cardiomyopathy (n = 53), and controls (n = 23). ST2 was correlated to N-terminal pro-brain natriuretic peptide, C-reactive protein, and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. The levels of ST2, ST2L, and IL-33 were measured (reverse transcriptase-polymerase chain reaction) in myocardial biopsies and leukocytes. The ST2 protein production was evaluated in human endothelial cells. The IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium.. The ST2 protein was elevated in aortic stenosis (103 [65, 165] pg/ml, p < 0.05) and congestive cardiomyopathy (194 [69, 551] pg/ml, p < 0.01) versus controls (49 [4, 89] pg/ml) and correlated with B-type natriuretic peptide (r = 0.5, p < 0.05), C-reactive protein (r = 0.6, p < 0.01), and LV end-diastolic pressure (r = 0.38, p < 0.03). The LV ST2 messenger ribonucleic acid was similar in aortic stenosis and congestive cardiomyopathy versus control (p = NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. The IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r = 0.97, p < 0.001).. In human hypertrophy and failure, serum ST2 correlates with the diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.

Topics: Aged; C-Reactive Protein; Case-Control Studies; Diastole; Endothelium, Vascular; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Leukocytes; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Prognosis; Receptors, Cell Surface

We studied systematically, for the first time, the utility of the six-minute walk test (6MWT) in Chagas disease. The walked distance at 6MWT correlated negatively with the increased circulating levels of monocyte chemoattractant protein (MCP-1, r=-0.358, p=0.04) and natriuretic peptide type B (BNP, r=-0.349, p=0.04), as well as positively with ejection fraction deterioration (r=0.451, p=0.004), indicating that submaximal functional capacity of chagasic patients is related to the severity of the cardiopathy. 6MWT may constitute an auxiliary tool in the evaluation of the clinical status of Chagas disease patients.

Topics: Chagas Cardiomyopathy; Chemokine CCL2; Exercise Test; Exercise Tolerance; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Stroke Volume; Time Factors

Immune activation is well established in patients with chronic heart failure and reduced ejection fraction (HF and reduced EF) and is associated with an impaired prognosis. Patients with heart failure and preserved ejection fraction (HF and preserved EF) have an impaired prognosis as well. It is not known whether they have signs of immune activation.. We studied patients with HF and preserved EF (n=17, NYHA II [n=7]/III [n=10]) and patients with HF and reduced EF (n=17 NYHA II [n=1]/III [n=16]) and 20 controls. Echocardiography demonstrated preserved ejection fraction (LVEF 59+/-9%), but LV hypertrophy in patients with preserved EF as compared with patients with reduced EF (LVEF 23+/-5%). We evaluated levels of TNFalpha, its receptors (sTNFR-1 and 2), IL-6, IL-10 and NT-proBNP.. TNFalpha, was highest in HF with reduced EF (2.87+/-0.65 vs 1.67+/-0.58 pg/mL, p<0.001) compared to preserved EF and similar between HF with preserved EF and controls. However, sTNFR1 (1618+/-384 vs 1017+/-302 pg/mL, p<0.001) and sTNFR2 levels (3554+/-916 vs 2041+/-586 pg/mL, p<0.001) in HF with preserved EF were significantly higher compared with controls. The same was true for IL-6, IL-10 and NT-proBNP. The highest cytokine and NT-proBNP levels were present in HF with reduced EF. There was a negative correlation between TNFalpha, and LVEF (r=- 0.700; p<0.0001) and positive correlations between sTNFR1 and 2 with NT-proBNP.. Patients with HF and preserved EF already show signs of systemic-immune activation which may contribute to the impaired prognosis and the progression to HF with reduced EF.

Topics: Aged; Aged, 80 and over; Cytokines; Female; Heart Failure; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Signal Transduction; Stroke Volume; Ventricular Function, Left

We used cardiac surgery as a model of acute inflammatory response to evaluate the role of the inflammatory mediators in influencing the number of circulating endothelial progenitor cells (EPCs).. In 38 coronary artery by-pass grafting (CABG) [28M/10F] and in 54 valvular [28M/26F] patients the numbers of EPCs and the serum levels of IL-1ra, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), high sensitivity C-reactive protein (hsCRP) and NT-proBNP were determined before (T1), 72h (T2), and 10 days after cardiac intervention (T3). Peripheral blood EPCs were measured by flow cytometric analysis and were defined as CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+.. We demonstrate that the cardiac surgery reduces, 72h after intervention, the number of all the three types of EPCs with a contemporary marked increase of pro-inflammatory and anti-inflammatory cytokines and NT-proBNP levels. At baseline, EPC number was inversely related with age. At multiple linear regression analysis, after adjusting for age, cardiovascular risk factors and medications, age and IL-8 serum levels were significantly related to EPC number. At T2, an inverse relationship between NT-proBNP and the number of EPCs was found in the whole study population. At T3, 10 days after the intervention, at multivariate linear regression analysis, IL-10 and IL-1ra serum levels were significantly and positively associated with EPC number.. This study provides new insights into the relationship between inflammatory activation and mobilisation of EPCs in patients underwent cardiac surgery, by showing that NT-ProBNP and cytochemokines mediate the EPC changes in acute and post-acute response to the inflammatory stimulus of intervention.

Topics: Acute-Phase Reaction; Aged; Aged, 80 and over; C-Reactive Protein; Coronary Artery Bypass; Cytokines; Endothelial Cells; Female; Flow Cytometry; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cells; Vascular Endothelial Growth Factor A

Adult heart failure (HF) has been shown to be associated with neuroendocrine and inflammatory activation. We hypothesize that neuroendocrine and inflammatory activation also associate with symptom severity and echocardiographic measurements in pediatric HF.. Nineteen children with HF were divided into 3 symptom severity groups. Measurements were made of left ventricular (LV) ejection fraction, LV shortening fraction (LVSF), LV shortening fraction Z score (LVSFz), and LV end-systolic (LVSDz) and diastolic diameter Z scores. Blood levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha, and soluble tumor necrosis factor receptor II were measured.. NT-proBNP and hsCRP were significantly elevated with more severe symptoms (P < or = .003) and discriminated between clinical severity groups (volume under the receiver operating characteristic surface = 0.58 and 0.62, P = .007 and P = .002, respectively). NT-proBNP was negatively associated with LV ejection fraction, LVSF, and LVSFz (P < or = .05) and positively associated with LVSDz (P < .001). High-sensitivity C-reactive protein was negatively associated with LVSF (P = .02) and positively associated with NT-proBNP (P = .03). Tumor necrosis factor alpha was negatively associated with LVSF and LVSFz (P < or = .03) and positively associated with LVSDz and NT-proBNP (P < or = .02). Soluble tumor necrosis factor receptor II was negatively associated with LVSFz (P = .03).. Neuroendocrine and inflammatory activation are associated with more severe symptoms and worse cardiac characteristics in pediatric HF. Blood levels of these biomarkers could be used to better assess the severity of HF in children.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Inflammation; Male; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Risk Factors; ROC Curve; Severity of Illness Index; Stroke Volume; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Inflammation plays a pathogenic role in the development of chronic heart failure (CHF). Increasing evidence shows that CD40-CD40 ligand (CD40L) interaction plays a pathogenic role in inflammatory disorders. We assessed whether CD40 ligand expression was abnormal in patients with CHF.. Twenty normal controls and 86 patients with CHF were investigated. The expression of CD40L on platelets was analyzed by indirect-immunofluorescence flow cytometry, and the soluble CD40L (sCD40L) level was determined by a commercially available enzyme-linked immunosorbent assay (ELISA). B type natriuretic peptide (BNP) was measured by radioimmunoassay.. All patients with CHF showed a significant increased expression of CD40L (32.3+/-13.9 MFI) on platelets and sCD40L levels (20.5+/-8.6 microg/l) compared with controls(p<0.0001). CD40L expression on platelets and sCD40L levels positively correlated with New York Heart Association (NYHA) functional class, left ventricular ejection fraction and BNP levels in CHF.. Patients with CHF showed increased expression of CD40L system, which may create a pathogenic role in the development and progression of CHF.

Topics: Aged; Blood Platelets; CD40 Ligand; Chronic Disease; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Platelet Activation; Stroke Volume

Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), prior studies have found that smokers with AMI have lower mortality rates than nonsmokers, a phenomenon often termed 'smoker's paradox'. The present study was designed to examine the etiology of 'smoker's paradox', especially with respect to the association with inflammation. The subjects included 528 consecutive AMI patients who were admitted within 24 hours of onset and underwent successful coronary intervention. Of the 528 subjects, 232 (44%) were smokers. The cardiac mortality rates over a 6 month period was significantly lower in the smoking group than the nonsmoking group (3% versus 9%, P = 0.01). There were significantly more male patients in the smoking group, and the smoking group was significantly younger than the nonsmoking group (P < 0.0001). The value of high sensitivity C-reactive protein (hs-CRP) on admission and 24 hours after onset, and serum amyloid A protein (SAA) were significantly higher, and acute phase BNP was significantly lower (hs-CRP on admission 1.36 +/- 1.03 mg/dL versus 0.75 +/- 0.82 mg/dL, P = 0.02, hs-CRP at 24 hours 3.86 +/- 4.32 mg/dL versus 2.90 +/- 3.46 mg/dL, P = 0.008, SAA; 288 +/- 392 microg/dL versus 176 +/- 206 microg/dL, P < 0.05, BNP; 248 +/- 342 pg/mL versus 444 +/- 496 pg/mL, P = 0.0002) in the smoking group than in the nonsmoking group. The early ST-segment resolution rate was higher in the smoking group compared with the nonsmoking group (80% versus 66%, P = 0.003). The reason why smokers with AMI have lower mortality rates than nonsmokers, the so-called 'smoker's paradox', is believed to be because smoking induces inflammation and smokers may have less damage to microvascular function after primary percutaneous coronary intervention.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; C-Reactive Protein; Female; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Serum Amyloid A Protein; Smoking

Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response. During and after cardiac surgery, we examined the pattern of cytokine release of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha, to investigate inflammatory response. We analyzed N-terminal pro brain-type natriuretic peptide (NT-proBNP) as a marker of ventricular function.. Consecutive patients (n = 58) undergoing elective cardiac surgery with extra-corporeal circulation were recruited into the study. Blood samples for analysis of the biochemical markers were taken at seven time points for cytokines and TNF, and three for Nt-proBNP.. All markers increased significantly after CPB. IL-6 and IL-8 levels were higher in men. IL-8 was related to a need for inotropic support. IL-6 was related to the time of CPB (P = 0.004), aortic clamping (P = 0.013), length of stay in intensive care unit (ICU) (P = 0.004) and mechanical ventilation for more than 12 h (P = 0.006). The levels of NT-proBNP were higher in cases of ventricular dysfunction (P = 0.003) and functional class III/IV (P = 0.001). The postoperative values were related to age (P < 0.05), creatinine values (P < 0.001), mechanical ventilation time (P < 0.001) and stay in the ICU (P = 0.001).. Our data indicate a relationship between cytokine levels and sex, time of CPB and aortic clamping, The increase of cytokines correlates with a need for inotropic support, mechanical ventilation and length of stay in ICU. We confirmed the predictive role, and its utility in the risk stratification of the NT-proBNP, and its importance in early diagnosis of postoperative ventricular dysfunction.

Topics: Age Factors; Aged; Biomarkers; Cardiac Surgical Procedures; Critical Care; Elective Surgical Procedures; Female; Heart Arrest; Humans; Inflammation; Interleukin-6; Interleukin-8; Length of Stay; Male; Natriuretic Peptide, Brain; Peptide Fragments; Respiration, Artificial; Tumor Necrosis Factor-alpha; Ventricular Function

The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly.. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index).. During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit.. Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cystatin C; Cystatins; Humans; Inflammation; Longitudinal Studies; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency; Risk Assessment; Risk Factors; Troponin I; Ventricular Dysfunction, Left

Cardiovascular disease is a major cause of death in patients with systemic lupus erythematosus (SLE) especially during the late phase of the disease. This study was conducted to evaluate B-type natriuretic peptide (BNP) levels in female SLE patients without cardiac symptoms and to investigate whether BNP levels correlated with echocardiographic findings. We studied 59 women with SLE and 33 healthy women. SLE patients with history of cardiac disease, diabetes mellitus, hypertension, and other inflammatory diseases were excluded from the study. All subjects had a complete history and physical examination. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE disease activity index (SLEDAI). BNP levels were determined, and transthoracic echocardiography were performed in all subjects. There was no difference between SLE patients and controls in terms of age, blood pressure, smoking status, plasma glucose, creatinine levels, and lipid profiles. Nine patients had SLEDAI score greater than 5. All subjects had an EF greater than 55%. Diastolic dysfunction was more frequent in lupus patients than in controls (15 [25.4%] vs. 2 [6%]; p = 0.022). BNP levels of SLE patients were significantly higher than controls (median 17.9 range [5-211] pg/ml vs. median 14.7 range [5-39.7] pg/ml; p = 0.033). Twenty-seven of the SLE patients (46%) and seven of the controls (21%) had BNP levels greater than or equal to 20 pg/ml (p = 0.019). There were no differences in BNP levels of SLE patients with and without diastolic dysfunction (median 17.8 range [5-117] pg/ml vs. median 18.5 range [5-211] pg/mL; p = NS). BNP levels were positively correlated with left atrium diameter (r (2) = 0.39, p = 0.001). BNP levels did not correlate with erythrocyte sedimentation rate/C-reactive protein levels, SLEDAI scores, total steroid dosage used, or other echocardigraphic parameters. BNP levels were increased in female SLE patients without cardiac symptoms as compared to healthy controls. Although none of the SLE patients in our study had clinical signs of ischemic heart disease, increased levels of BNP in SLE patients might be a reflection of a ischemic myocardial tissue.

Topics: Adult; Age Factors; Blood Pressure; Cardiovascular Diseases; Echocardiography; Female; Humans; Inflammation; Lupus Erythematosus, Systemic; Middle Aged; Models, Statistical; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors

Ventricular arrhythmia is the main cause of sudden cardiac death. Intracardiac strain, myocardial and extracellular matrix remodelling, and subsequent myocardial fibrosis are involved in arrhythmia pathogenesis. The present study investigates the relationship between cardiac fibrosis [procollagen type I aminoterminal peptide (PINP), procollagen type III aminoterminal peptide (PIIINP), TIMP1, membrane metalloproteinase I], pressure overload [brain natriuretic peptide (BNP)] inflammation [high sensitivity (hs)-C-reactive protein] serum markers, and the incidence of ventricular tachycardia (VT) in implantable cardioverter-defibrillators (ICD) recipients.. Serum markers were collected in 121 patients implanted for spontaneous sustained VT and a prior history of myocardial infarction. VT incidence was obtained during ICD interrogation. Over a 1 year period, 38 patients (31%) experienced at least 1 VT. In a multivariate analysis, a left ventricular ejection fraction <0.35 (OR = 2.19, 95%CI 1.00-4.79, P = 0.049), an increased serum BNP (OR = 3.75, 95%CI 1.46-9.67, P = 0.014), an increased hs-C-reactive protein (OR = 3.2, 95%CI 1.26-8.10, P = 0.006), an increased PINP (OR = 3.71, 95%CI 1.40-9.88, P = 0.009), and a decreased PIIINP (OR = 0.21, 95%CI 0.08-0.59, P = 0.003) were associated with a higher VT incidence.. In coronary artery disease patients: (1) BNP is not only a marker of left ventricular dysfunction, but also a marker of VT; (2) combined 'high PINP and low PIIINP' is a strong VT marker; and 3) inflammatory process is involved in VT pathogenesis.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Defibrillators, Implantable; Female; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Procollagen; Prospective Studies; Research Design; Risk; Tachycardia, Ventricular

Anaemia is associated with elevated levels of natriuretic peptides. Whether the association of anaemia with natriuretic peptides is independent of other cardiovascular risk factors is unclear.. This was a cross-sectional study of 809 ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF). We evaluated the extent to which the relationship between haemoglobin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) was explained by differences in cardiovascular risk factors, inflammation, and kidney dysfunction.. Of the 809 participants, 189 (23%) had anaemia (haemoglobin <13 g/dL). Haemoglobin (as a continuous variable) was inversely associated with log NT-proBNP (beta coefficient -.28, p<.0001). This association was considerably attenuated after accounting for cardiovascular risk factors, C-reactive protein, and kidney dysfunction. However, haemoglobin remained independently associated with log NT-proBNP even after adjustment for these variables (beta coefficient -.11, p=0.0003). Each 1 g/dL decrease in haemoglobin was associated with a 20% greater odds of having NT-proBNP in the highest quartile.. The relationship between anaemia and NT-proBNP is largely explained by differences in cardiovascular risk factors, ventricular function, myocardial ischaemia, inflammation, and kidney function. Nonetheless, haemoglobin appears to be inversely associated with NT-proBNP even after adjustment for these risk factors.

Topics: Aged; Aged, 80 and over; Anemia; Coronary Disease; Cross-Sectional Studies; Female; Hemoglobins; Humans; Inflammation; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population.. In a cohort of 216 ACS patients, NT-proBNP (Elecsys; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2-4 h) and a later specimen (9 h; 9-9 h), and used the later specimens' biomarker concentrations for risk stratification.. An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan-Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers.. IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.

Topics: Acute Coronary Syndrome; Aged; Chemokine CCL2; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Risk Factors

Increased concentrations of biomarkers reflecting myocardial stress such as cardiac troponin I and T and brain natriuretic peptide (BNP) have been observed following strenuous, long-lasting endurance exercise. The pathophysiological mechanisms are still not fully elucidated and the interpretations of increased post-exercise concentrations range from (i) evidence for exercise-induced myocardial damage to (ii) non-relevant spurious troponin elevations, presumably caused by assay imprecision or heterophilic antibodies. Several lines of evidence suggest that inflammatory processes or oxidative stress could be involved in the rise of NT-proBNP and Troponin observed in critically ill patients with sepsis or burn injury. We tested the hypothesis that inflammatory or oxidative stress is also responsible for exercise-induced cardiomyocyte strain in a large cohort of triathletes following an Ironman triathlon. However, the post-race increase in cardiac troponin T and NT-proBNP was not associated with several markers of exercise-induced inflammation, oxidative stress or antioxidant vitamins. Therefore, we clearly need more studies with other inflammatory markers and different designs to elucidate the scientific background for increases in myocardial stress markers following strenuous endurance events.

Topics: Biomarkers; Exercise; Humans; Inflammation; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Predictive Value of Tests; Troponin

Immune system activation and oxidative stress are involved in the pathogenesis of heart failure (HF). We aimed to test the hypothesis that upgrading from right ventricular pacing (RVp) to biventricular pacing (BiVp) can counteract these phenomena.. 28 HF patients, with BiVp were switched to RVp for one week, and then returned to BiVp. Immediately prior to, and 48 h after the return to BiVp, left ventricular (LV) systolic function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NTproBNP), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL6), nitric oxide metabolites (NO(x)) and malondialdehyde (MDA) were assayed.. LV systolic function significantly improved 48 h after switching from RVp to BiVp: Ao-VTI (p<0.001), SV (p<0.001) and CO (p<0.001), and mitral regurgitation significantly decreased (p=0.003). At the same time, indices of peripheral immune activation decreased: TNF-alpha (p=0.02) and IL6 (p<0.001). MDA decreased (p<0.001), whereas NO(x) increased (p=0.04). NTproBNP and CRP did not change. In addition, in "responders" (i.e. CO increase >10% during BiVp vs. RVp) NTproBNP decreased and NO(x) increased. However, during BiVp, the decreases in TNF-alpha, IL6, and MDA occurred both in responders and in non-responders and were accompanied by a reduction in mitral regurgitation.. The beneficial effect of BiVp compared to RVp extends beyond improving cardiac haemodynamics and comprises a decrease in immune activation accompanied by an increase in serum NO(x) and decrease in serum MDA.

Topics: Aged; Aged, 80 and over; Cardiac Output, Low; Cardiac Pacing, Artificial; Chronic Disease; Female; Heart Ventricles; Humans; Inflammation; Interleukin-6; Male; Malondialdehyde; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Pacemaker, Artificial; Systole; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Adiponectin, an adipocyte-derived hormone, appears to be a modulator of lipid metabolism and systemic inflammation and is present in particularly low concentrations in patients with coronary heart disease (CHD). However, the clinical importance of adiponectin in individuals at markedly high risk for future cardiovascular morbidity and mortality has not been fully elucidated. We examined the associations between serum adiponectin and several biomarkers related to cardiovascular disease and heart failure in a large high-risk population comprising patients with prevalent CHD.. We measured fasting adiponectin, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and markers of lipoprotein metabolism in 1174 patients with CHD.. After adjustment for age and sex, adiponectin was associated with HDL-cholesterol (HDL-C; r = 0.25; P <0.0001), NT-proBNP (r = 0.17; P <0.0001), and plasma triglyceride (r = -0.21; P <0.0001) concentrations. There was, however, no statistically significant association between adiponectin and markers of systemic inflammation. In partial correlation analyses further adjusted for body mass index, alcohol intake, smoking status, presence of diabetes and/or hypertension, lipid-lowering drug therapy, and fasting plasma glucose, adiponectin remained significantly associated with HDL-C (r = 0.21; P <0.0001), NT-proBNP (r = 0.15; P <0.0001), and plasma triglycerides (r = -0.16; P <0.0001).. Serum adiponectin is associated with the presence of atherogenic dyslipidemia and with NT-proBNP concentration but not with markers of systemic inflammation in patients with manifest CHD. Thus, atherogenic dyslipidemia may link adiponectin with the progression of atherosclerosis. Moreover, serum adiponectin may be related to BNP in patients with CHD.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; Biomarkers; Coronary Disease; Cross-Sectional Studies; Dyslipidemias; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Risk Factors; Socioeconomic Factors; Ventricular Function, Left

Topics: Acute Disease; C-Reactive Protein; Disease Progression; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Ventricular Function

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

Topics: Aged; Cardiac Pacing, Artificial; Female; Heart Failure; Heart Ventricles; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Adiponectin; Atherosclerosis; Biomarkers; Coronary Disease; Dyslipidemias; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors

Plasma levels of inflammatory markers are increased in chronic heart failure (HF) and are also subclinical indicators of future HF. Inflammation is strictly correlated with clotting activation, but the association between inflammation, hypercoagulability and prognosis in HF has not been previously reported.. Markers of inflammation (interleukin-6; IL-6, and C-reactive protein; CRP) and hypercoagulability (D-dimer; DD, and thrombin-antithrombin III complex; TAT) were prospectively assessed in 214 subjects with New York Heart Association (NYHA) functional class II-IV HF. During a median follow-up of 8.5 months, 32 patients had an event: 13 died and 19 were hospitalized because of worsening of HF. IL-6, DD and TAT levels were all significantly associated with increased risk of death after adjustment for other known HF prognostic factors (age, gender, traditional cardiovascular risk factors, NYHA class, systolic left ventricular function, renal failure, hemoglobin, serum sodium) in a Cox multivariate proportional hazard model (P = 0.003, P = 0.01 and P = 0.02, respectively). When these markers were added simultaneously to the known prognostic factors in a new Cox multivariate model, only DD levels were significant predictors of mortality (hazard ratio [95% confidence interval; CI]: 11 [2.7-45.1], P = 0.001). The Kaplan-Meier curve revealed a significantly better outcome in patients with DD below 450 ng mL(-1). NT-pro-BNP was the only significant predictor of rehospitalization (HR [95% CI]: 5.3 [2.0-13.8], P < 0.001).. Hypercoagulability and inflammation, as assessed by DD, TAT and IL-6 levels, are associated with an increased mortality risk in HF.

Topics: Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Blood Coagulation Disorders; C-Reactive Protein; Cardiac Output, Low; Female; Fibrin Fibrinogen Degradation Products; Heart Function Tests; Humans; Inflammation; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Hydrolases; Risk Factors

Cardiac resynchronization therapy is a modality with proven morbidity and mortality benefit in advanced systolic heart failure. Nevertheless, not all patients respond favorably to CRT. Natriuretic peptides and inflammatory markers are elevated in congestive heart failure and reflect disease severity.. To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT.. The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus, Post-implantation levels were determined 2 weeks post-procedure in the PVB. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure.. At baseline, coronary sinus levels of BNP but not hsCRP were significantly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 +/- 102.5 pg/ml, 95% confidence interval 24.2-434, P< 0.0001; hsCRP mean difference 5.2 +/- 2.4 mg/dl, 95% CI 0.3-10.1, P= 0.001). During a mean follow-up of 17.7 +/- 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF. Baseline New York Heart Association and CSBNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations.. BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict clinical response and may guide patient management.

Topics: Acute Disease; Aged; Biomarkers; C-Reactive Protein; Cardiac Pacing, Artificial; Female; Follow-Up Studies; Heart Conduction System; Heart Failure; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Patient Admission; Predictive Value of Tests; Risk Factors; Systole; Time Factors; Treatment Outcome

Several studies have shown that longitudinal systolic function and left ventricular filling pressures, as assessed with tissue Doppler imaging, predict exercise capacity.. The aim of this study was to evaluate whether natriuretic peptides and inflammatory parameters can independently predict maximum oxygen uptake at peak exercise (VO2max) on top of tissue Doppler imaging-derived markers.. We evaluated 142 patients (age 70 +/- 6 years, 77% men) with known or suspected coronary artery disease and a preserved left ventricular ejection fraction (> or = 50%). All patients underwent bicycle spiroergometry, and N-terminal pro-B-type natriuretic peptide levels were determined. Cytokines (IL-6 and soluble tumor necrosis factor receptors 1 and 2) and high-sensitivity C-reactive protein were measured as inflammatory markers. Tissue Doppler imaging was applied to evaluate peak long axis systolic velocities (Sm) and early mitral annulus velocities (E'). Ratio of early transmitral flow (E) to E' was assessed as marker of left ventricular filling. Analysis of variance, comparing VO2max quartiles, was used to determine univariate predictors and linear regression to determine multivariate VO2max predictors.. Average VO2max was 18.5 +/- 5.7 mL/kg per minute (range 6-36.6). Compared with the highest quartile, patients with low VO2max were more frequently women (P < .0001). N-terminal pro-B-type natriuretic peptide and cytokine levels were significantly higher in the lower VO2max categories. Longitudinal myocardial velocities increased, and E/E' decreased along with increasing VO2max. In multivariate linear regression analysis, VO2max was independently predicted by sex, glucose, Sm, E/E', and cytokine levels.. Maximum oxygen uptake at peak exercise in patients with known or suspected coronary artery disease and preserved systolic function was independently predicted by inflammatory makers on top of tissue Doppler-derived systolic and diastolic function.

Topics: Aged; C-Reactive Protein; Coronary Artery Disease; Cytokines; Diastole; Echocardiography, Doppler; Exercise; Exercise Test; Female; Humans; Inflammation; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Systole; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Congestive heart failure (CHF) is associated with persistent immune activation. Medical therapy has been shown to exert only limited anti-inflammatory effects. Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in a subset of patients with heart failure, but it is not known whether this treatment affects the immune system as well. To test this hypothesis, eight patients with heart failure scheduled for CRT were investigated for immune activation before and 6 months after CRT treatment.. After 6 months, all patients had improved in NYHA-class and LVEF, and there was a statistically significant reduction in serum N-terminal pro brain natriuretic peptide (BNP). Furthermore, there was a statistically significant reduction in plasma levels of the chemokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) and the cytokine interleukin 6 (IL-6). We observed no changes in the levels of interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), or complement activation products. There was a significant correlation between changes in BNP and IL-6 (r = 0.74, P = 0.037).. Although based upon a limited number of patients, this report indicates that CRT reduces peripheral markers of immune activation in patients with CHF. Further large scale studies are warranted to verify these findings.

Topics: Aged; Aged, 80 and over; Cardiac Pacing, Artificial; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Membrane Cofactor Protein; Middle Aged; Natriuretic Peptide, Brain; Statistics, Nonparametric

Although an altered thyroid metabolism has been documented in patients with overt heart failure, no evaluation has been made of a heart-thyroid interaction in mildly symptomatic patients with idiopathic left ventricular dysfunction (ILVD). We wanted to assess the thyroid state in patients with ILVD.. Eighty-six patients (age 60 +/- 10 years) were enrolled into the study. Thyroxine (T4), triiodothyronine (T3), thyrotropin, brain and atrial natriuretic peptides (BNP, ANP), noradrenaline, aldosterone, renin activity, and interleukin-6 were measured. Patients were divided into three groups: Group N with LV ejection fraction (EF) > or = 50% (n = 28), Group I with LVEF > 35%-< 50% (n = 34), Group II with LVEF < or = 35% (n = 24). There was a significant correlation between T3 and LVEF (r = 0.25, P = .02) and a negative correlation between T3 and BNP (r = -0.37, P < .0001). At univariate analysis T3 was a predictor of LV dysfunction, whereas BNP was the most important predictor at multivariate analysis (P = .002). T3 was the only predictor of New York Heart Association class at multivariate analysis.. An altered thyroid profile characterized by a reduction in peripheral production of biologically active T3 is related to LV dysfunction and early symptoms of heart failure in patients with ILVD.

Topics: Aged; Cardiac Output, Low; Female; Hormones; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neurosecretory Systems; Predictive Value of Tests; Severity of Illness Index; Stroke Volume; Thyroid Gland; Thyroid Hormones; Triiodothyronine; Ventricular Dysfunction, Left

Cardiac hypertrophy is a complex and nonhomogenous response to various stimuli. In this study, we used high-density oligonucleotide microarray to examine gene expression profiles during physiological hypertrophy, pathological hypertrophy, and heart failure in Dahl salt-sensitive rats. There were changes in 404/3,160 and 874/3,160 genes between physiological and pathological hypertrophy and the transition from hypertrophy to heart failure, respectively. There were increases in stress response genes (e.g., heat shock proteins) and inflammation-related genes (e.g., pancreatitis-associated protein and arachidonate 12-lipoxygenase) in pathological processes but not in physiological hypertrophy. Furthermore, atrial natriuretic factor and brain natriuretic protein showed distinctive changes that are very specific to different conditions. In addition, we used a resampling-based gene score-calculating method to define significantly altered gene clusters, based on Gene Ontology classification. It revealed significant alterations in genes involved in the apoptosis pathway during pathological hypertrophy, suggesting that the apoptosis pathway may play a role during the transition to heart failure. In addition, there were significant changes in glucose/insulin signaling, protein biosynthesis, and epidermal growth factor signaling during physiological hypertrophy but not during pathological hypertrophy.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blotting, Northern; Cardiomegaly; Echocardiography; Epidermal Growth Factor; Gene Expression Profiling; Gene Expression Regulation; Heart Failure; Hypertrophy; Inflammation; Insulin; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Pancreatitis-Associated Proteins; Physical Conditioning, Animal; Rats; Rats, Inbred Dahl; RNA; Signal Transduction

The effects of patient-activated atrial defibrillation on subclinical myocardial injury are unknown. Using biochemical markers, this study assessed the effect of a single internal atrial shock delivered by the implantable atrial defibrillator on myocardial damage, neurohormonal activation and inflammation.. Twelve patients were implanted with a dual chamber defibrillator for the sole indication of drug refractory symptomatic persistent atrial fibrillation (AF). All had maximum defibrillation energy programmed to maximise the first shock success rate. Creatine kinase isoenzyme, troponin T, cortisol, catecholamines, C-reactive protein and brain natriuretic peptide were measured (i) during sinus rhythm, (ii) 8 h after onset of spontaneously occurring AF (before cardioversion) and (iii) 8 h following successful patient activated cardioversion.. There was no change in creatine kinase, troponin T, cortisol or C-reactive protein during AF or following internal cardioversion. Brain natriuretic peptide levels rose from a median value of 56 pg/ml during sinus rhythm (inter-quartile range 14-92 pg/ml) to 133 pg/ml during AF (30-262 pg/ml), p=0.002. There was a decrease 8 h after cardioversion to baseline (52 and 40-189 pg/ml), p=0.01. There were increases in serum adrenaline and noradrenaline levels during AF from 0.43 (0.12-0.61) to 0.58 pg/ml (0.39-0.80 pg/ml), p=0.002 and from 2.06 (1.61-2.59) to 2.83 nmol/l (2.43-3.46 nmol/l), p=0.02, respectively. These figures reverted to baseline levels 8 h post-cardioversion.. Internal atrial defibrillation does not result in myocardial injury. The onset of AF results in sympathetic activation and increased brain natriuretic peptide levels, which resolve following restoration of sinus rhythm.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Catecholamines; Chromatography, High Pressure Liquid; Creatine Kinase; Electric Countershock; Female; Follow-Up Studies; Humans; Hydrocortisone; Immunoassay; Inflammation; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nephelometry and Turbidimetry; Severity of Illness Index; Troponin T

Increased risk of cardiovascular disease has been reported in patients with primary hyperparathyroidism (PHPT). The aim of this study was to evaluate novel plasma risk markers of cardiovascular disease in patients with PHPT.. PHPT patients were evaluated with a control group. Patients who underwent parathyroidectomy were re-evaluated after 7 and 18 months.. Forty-five PHPT patients and 40 matched controls participated. Seventeen patients underwent parathyroidectomy.. Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha), lipids and blood pressure were measured. In 27 patients a bicycle exercise test and radionuclide angiography were performed, and repeated in those who underwent parathyroidectomy.. Plasma NT-proBNP, CRP and TNF-alpha, but not IL-6, were higher in patients with PHPT than in controls (P < 0.01 and P = 0.17, respectively). In patients with PHPT, NT-proBNP correlated with systolic blood pressure, left ventricular end-diastolic volume, and peak oxygen uptake (all P < 0.01). Log CRP correlated with systolic and diastolic blood pressure (both P < 0.05) and log IL-6 (P < 0.01). No significant correlations were observed between PTH or calcium and risk markers of cardiovascular disease. No decrease in NT-proBNP, markers of inflammation or blood pressure was observed after parathyroidectomy.. Our data suggest that hypertension or other factors, rather than plasma calcium or PTH, could explain the increased levels of the inflammatory markers and NT-proBNP in PHPT. We therefore suggest that aggressive treatment of hypertension should be initiated in patients with PHPT to try to reduce the increased cardiovascular mortality described in PHPT. Further prospective studies are needed to validate the suggestion that increased levels of NT-proBNP and inflammatory markers also represent strong prognostic markers of cardiovascular disease in patients with PHPT.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Bone Density; C-Reactive Protein; Case-Control Studies; Female; Humans; Hyperparathyroidism, Primary; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroidectomy; Peptide Fragments; Radionuclide Angiography; Regression Analysis

The natriuretic peptides, including human B-type natriuretic peptide (BNP), have been implicated in the regulation of cardiac remodeling. Because transforming growth factor-beta (TGF-beta) is associated with profibrotic processes in heart failure, we tested whether BNP could inhibit TGF-beta-induced effects on primary human cardiac fibroblasts. BNP inhibited TGF-beta-induced cell proliferation as well as the production of collagen 1 and fibronectin proteins as measured by Western blot analysis. cDNA microarray analysis was performed on RNA from cardiac fibroblasts incubated in the presence or absence of TGF-beta and BNP for 24 and 48 hours. TGF-beta, but not BNP, treatment resulted in a significant change in the RNA profile. BNP treatment resulted in a remarkable reduction in TGF-beta effects; 88% and 85% of all TGF-beta-regulated mRNAs were affected at 24 and 48 hours, respectively. BNP opposed TGF-beta-regulated genes related to fibrosis (collagen 1, fibronectin, CTGF, PAI-1, and TIMP3), myofibroblast conversion (alpha-smooth muscle actin 2 and nonmuscle myosin heavy chain), proliferation (PDGFA, IGF1, FGF18, and IGFBP10), and inflammation (COX2, IL6, TNFalpha-induced protein 6, and TNF superfamily, member 4). Lastly, BNP stimulated the extracellular signal-related kinase pathway via cyclic guanosine monophosphate-dependent protein kinase signaling, and two mitogen-activated protein kinase kinase inhibitors, U0126 and PD98059, reversed BNP inhibition of TGF-beta-induced collagen-1 expression. These findings demonstrate that BNP has a direct effect on cardiac fibroblasts to inhibit fibrotic responses via extracellular signal-related kinase signaling, suggesting that BNP functions as an antifibrotic factor in the heart to prevent cardiac remodeling in pathological conditions.

Topics: Adolescent; Blotting, Western; Butadienes; Cell Division; Cells, Cultured; Cyclic GMP; Enzyme Inhibitors; Extracellular Matrix Proteins; Fibroblasts; Fibrosis; Flavonoids; Gene Expression Profiling; Gene Expression Regulation; Humans; Inflammation; Male; MAP Kinase Signaling System; Middle Aged; Muscle Proteins; Natriuretic Peptide, Brain; Nitriles; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta; Ventricular Remodeling

An increase in circulating brain natriuretic peptide (BNP) but not atrial natriuretic factor (ANF) is observed coincident with cardiac allograft rejection that is reversed upon treatment with anti-lymphocyte therapy suggesting that pro-inflammatory cytokines may uniquely modulate BNP gene expression and secretion. This study tested pro-inflammatory cytokines or conditioned medium (CM) derived from mixed- lymphocyte reaction (MLR) cultures in their ability to modulate ANF or BNP mRNA expression, secretion, as well as BNP promoter activity in cultured neonatal rat cardiocytes. IL-1 beta and TNF-alpha elicited a significant dose- and time-dependent increase in BNP mRNA, and secretion, whereas, ANF mRNA levels and secretion did not change. IL-1 beta and TNF-alpha rapidly increased phosphorylated p38 MAP kinase abundance and activity. Inhibition of p38 MAP kinase with SB203580 abolished IL-1 beta- and TNF-alpha-stimulated increase in BNP mRNA, promoter activity and secretion. MLR-CM in 20%, 50% and 100% proportions increased BNP but not ANF secretion. The MLR-induced increases in BNP secretion were completely abolished by SB203580 pre-treatment. These investigations show that exposure of cultured rat cardiocytes to specific pro-inflammatory cytokines as well as MLR-CM results in the only known instance of upregulation of cardiac BNP at the transcriptional and translational levels without a corresponding increase in ANF gene expression. Furthermore, these effects are dependent on signaling by p38 MAP kinase. In all, the findings reveal a unique dis-coordinated expression of BNP and ANF to inflammatory cytokines and offers an opportunity to better understand the differential regulation of these two cardiac-derived endocrine hormones that share receptors as well as biological properties.

Topics: Animals; Animals, Newborn; Blotting, Northern; Blotting, Western; Cells, Cultured; Culture Media, Conditioned; Cytokines; Densitometry; Dose-Response Relationship, Drug; Enzyme Activation; Gene Expression Regulation; Imidazoles; Inflammation; Interferon-gamma; Interleukin-1; Lymphocytes; Myocardium; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Peptides; Phosphorylation; Promoter Regions, Genetic; Protein Biosynthesis; Pyridines; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Time Factors; Transcription, Genetic; Transcriptional Activation; Transfection; Transplantation; Tumor Necrosis Factor-alpha; Up-Regulation

Topics: Biomarkers; Blood Pressure; Body Water; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Edema; Heart Failure; Humans; Inflammation; Kidney Failure, Chronic; Malnutrition; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Renal Dialysis

Natriuretic peptides (NPs), which consist of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively), are characterized as cardiac or vascular hormones that elicit their biological effects by activation of the cGMPcGMP-dependent protein kinase (cGK) pathway. We recently reported that adenoviral gene transfer of CNP into rabbit blood vessels not only suppressed neointimal formation but also accelerated reendothelialization, a required step for endothelium-dependent vasorelaxation and antithrombogenicity. Accordingly, we investigated the therapeutic potential of the NPscGMPcGK pathway for vascular regeneration. In transgenic (Tg) mice that overexpress BNP in response to hindlimb ischemia, neovascularization with appropriate mural cell coating was accelerated without edema or bleeding, and impaired angiogenesis by the suppression of nitric oxide production was effectively rescued. Furthermore, in BNP-Tg mice, inflammatory cell infiltration in ischemic tissue and vascular superoxide production were suppressed compared with control mice. Ischemia-induced angiogenesis was also significantly potentiated in cGK type I Tg mice, but attenuated in cGK type I knockout mice. NPs significantly stimulated capillary network formation of cultured endothelial cells by cGK stimulation and subsequent Erk12 activation. Furthermore, gene transfer of CNP into ischemic muscles effectively accelerated angiogenesis. These findings reveal an action of the NPscGMPcGK pathway to exert multiple vasculoprotective and regenerative actions in the absence of apparent adverse effects, and therefore suggest that NPs as the endogenous cardiovascular hormone can be used as a strategy of therapeutic angiogenesis in patients with tissue ischemia.

Topics: Animals; Atrial Natriuretic Factor; Blood Vessels; Cells, Cultured; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Gene Expression; Gene Transfer Techniques; Humans; Inflammation; Ischemia; Mice; Mice, Knockout; Mice, Transgenic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neovascularization, Physiologic; Regeneration

Topics: Angioplasty, Balloon, Coronary; Atrial Natriuretic Factor; C-Reactive Protein; Carotid Artery Diseases; Clinical Trials as Topic; Combined Modality Therapy; Coronary Disease; Electrocardiography; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Myocardial Revascularization; Natriuretic Peptide, Brain; Stents

In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

Topics: Adult; Aged; Aging; Endothelium, Vascular; Female; Heart Failure; Hot Temperature; Humans; Inflammation; Inflammation Mediators; Iontophoresis; Male; Microcirculation; Natriuretic Peptide, Brain; Regional Blood Flow; Skin; Vasodilation; Vasodilator Agents

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Coronary Disease; Creatinine; Glycated Hemoglobin; Humans; Inflammation; Kidney Diseases; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Syndrome

We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy.. Biochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non-ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome.. Levels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI.. Patients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy.. N-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.

Topics: Adult; Aged; Angina, Unstable; Biomarkers; Coronary Angiography; Coronary Disease; Echoencephalography; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Necrosis; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Troponin T