leptin and Heart-Failure

Obesity has recently emerged as one of the most severe health concerns. Obesity is a key autonomous risk factor for heart failure and contributes to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and metabolic abnormalities. Obesity is caused by a metabolic imbalance, which occurs when calories burnt are fewer than the number of calories consumed. There are several pathways accountable for the adverse impacts of obesity on the cardiovascular system. Inflammatory cell infiltration develops in the adipose tissue, the pancreas, and other issues similar to the progression of obesity. Inflammation is triggered by immune cells that invade dysfunctional adipose tissue. The atherosclerotic inflammation phase, related to obesity, induces coronary calcification. Obesity is linked to elevated levels of leptin and high blood pressure. Leptin causes systemic vasoconstriction, sodium retention, and increased blood pressure by influencing the synthesis of nitric oxide and activating the sympathetic nervous system. Obesity is a well-known risk factor for CVD and is one of the leading causes of the greater risk of diseases, including dyslipidemia, hypertension, depression, metabolic syndrome, atrial fibrillation, and heart failure in adults and children. When used with dietary improvements, antiobesity drugs improve the probability of experiencing clinically healthy (5%) weight loss. This review aimed to address the consequences of obesity on cardiac structure and function, risk factors, the impact of the obesity paradox, pharmacological treatment strategies for managing and recommended exercise and diet.

Topics: Adult; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Inflammation; Leptin; Obesity

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

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Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Nephropathies; Heart; Heart Failure; Humans; Hypoglycemic Agents; Intra-Abdominal Fat; Kidney Tubules; Leptin; Models, Biological; Myocardium; Obesity; Renal Insufficiency; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits.

Topics: Adipose Tissue; Adiposity; Aldosterone; Heart Failure; Heart Ventricles; Humans; Leptin; Neprilysin; Obesity; Phenotype; Prognosis; Risk Factors; Signal Transduction; Stroke Volume; Sympathetic Nervous System; Ventricular Function, Left

The identification of the adipocyte as a source of production of biologically-active peptides has materialized into an active area of research related to the role of these peptides in physiology and pathophysiology. Moreover, this research has resulted in the identification of the adipocyte as an endocrine organ producing potent bioactive compounds. An increasing number of these adipokines are being identified, the first of which was leptin, a product of the obesity gene whose primary function is to act as a satiety factor but which is now known to exert a myriad of effects. It is now recognized that virtually all adipokines produce effects on numerous organ systems including the heart and many of these, including leptin, are produced by cardiac tissue. Here we focus primarily on the diverse effects of leptin on the heart especially as it pertains to hypertrophy and discuss the potential cell signaling mechanisms underlying their actions. Current evidence suggests that leptin is a cardiac hypertrophic factor and from clinical studies there is evidence that hyperleptinemia is associated with cardiovascular risk especially as it pertains to heart failure. While more substantial research needs to be carried out, leptin may represent a potential link between obesity, which is associated with hyperleptinemia, and increased cardiovascular risk.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiovascular System; Disease Progression; Heart Failure; Humans; Leptin; Models, Cardiovascular; Receptors, Leptin; Signal Transduction

In the study of heart failure (HF), biomarkers have served as an important tool for diagnostic, therapeutic and prognostic assessment. Their main categories in the area of HF are markers of ventricular dysfunction, inflammation, metabolism, neurohormones, oxidative stress, myocardial injury and extracellular matrix remodeling.. Leptin contributes to the modulation of metabolism, respiratory control and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in patients with HF have shown conflicting results in previous studies. Most studies have suggested that serum leptin levels may be increased in patients without cachexia. On the other hand, leptin levels are decreased in patients with advanced HF and cardiac cachexia or specific HF etiologies such as Chagas' disease. Other studies have showed that leptin levels were related to exercise intolerance. The only exception of the direct correlation of serum leptin levels with severity of CHF is present in CHF with cardiac cachexia, because patients with cardiac cachexia have plasma leptin concentrations lower than those without cardiac cachexia.. These findings can make leptin an important diagnostic and prognostic marker for HF and be included in routine investigation of patients with HF.

Topics: Biomarkers; Heart Failure; Humans; Leptin

Leptin is a 16 kDa peptide that was first identified in 1994 through positional cloning of the mouse obesity gene. Although the primary function of leptin is to act a satiety factor through its actions on the hypothalamus, it is now widely recognized that leptin can exert effects on many other organs through activation of its receptors, which are ubiquitously expressed. Leptin is secreted primarily by white adipocytes, but it is also produced by other tissues including the heart where it can exert effects in an autocrine or paracrine manner. One of these effects involves the induction of cardiomyocyte hypertrophy, which appears to occur via multiple cell signalling mechanisms. As adipocytes are the primary site of leptin production, plasma leptin concentrations are generally positively related with body mass index and the degree of adiposity. However, hyperleptinemia is also associated with cardiovascular disease, including heart failure, in the absence of obesity. Here we review the potential role of leptin in heart disease, particularly pertaining to its potential contribution to myocardial remodelling and heart failure, as well as the underlying mechanisms. We further discuss potential interactions between leptin and another adipokine, adiponectin, and the potential implications of this interaction in terms of fully understanding leptin's effects.

Topics: Adiponectin; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Body Composition; Calcineurin; Cardiomegaly; Heart Failure; Humans; Leptin; Mitochondria, Heart; Probiotics; Proteins; Receptors, Leptin; rho-Associated Kinases; Signal Transduction

Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

Topics: Appetite; Biomarkers; Cachexia; Chronic Disease; Cytokines; Endocrine System; Ghrelin; Heart Failure; Humans; Hypothalamus; Leptin; Neuropeptide Y; Pro-Opiomelanocortin; Prognosis

Chronic heart failure (CHF) is a major public health problem. The failure to provide peripheral tissues with sufficient amounts of oxygen is accompanied by maladaptive responses that include pathophysiological pathways that may lead to an anabolic-catabolic imbalance with the development of cardiac cachexia. This review aims to highlight players of the catabolic-anabolic imbalance, regulators or appetite, and other mediators that are involved in the progression of CHF to cachexia.. Clinical research has buttressed the view that deficiencies or resistance to growth hormone and testosterone plays an important role in the pathophysiology of CHF. The role of appetite regulation in the development of cardiac cachexia is also subject of recent studies. The resistance of CHF patients to the effects of appetite-stimulating peptide ghrelin may be one of the contributing factors. These circumstances drive muscle, bone, and fat wasting. Plasma levels of the adipokines leptin and adiponectin may have a role in the detection of such wasting processes.. Hormonal signaling pathways play an essential role in the development of cardiac cachexia. Recent findings enhance our understanding of the complex interplay between these regulators and may serve as a hub for the development of therapeutic interventions to prevent or potentially even to treat cardiac cachexia.

Topics: Adiponectin; Appetite; Cachexia; Chronic Disease; Ghrelin; Heart Failure; Human Growth Hormone; Humans; Leptin; Peptide Hormones; Prognosis; Signal Transduction; Testosterone

Heart failure goes beyond mechanical dysfunction and involves an interplay of multiple pathophysiologic mechanisms, including inflammation, tissue remodeling, neurohormonal and endocrine signaling, and interactions with the renal and nervous systems. This article highlights some novel biomarkers that may aid in diagnosis, treatment, and prognosis of acute heart failure, specifically focusing on ST2, endoglin, galectin-3, cystatin C, neutrophil gelatinase-associated lipocalin, midregional pro-adrenomedullin, chromogranin A, adiponectin, resistin, and leptin and their emerging clinical roles.

Topics: Acute Disease; Acute-Phase Proteins; Adiponectin; Adrenomedullin; Antigens, CD; Biomarkers; Chromogranin A; Cystatin C; Endoglin; Galectin 3; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Leptin; Lipocalin-2; Lipocalins; Proto-Oncogene Proteins; Receptors, Cell Surface; Resistin

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain

Owing to the increased incidence of obesity and its association with heart failure, there is now great interest in elucidating the underlying molecular mechanisms linking these pathologies. Since the discovery of adipose-derived hormones and cytokines, their important regulatory role in myocardial function has emerged. The events that these adipokines can regulate include alterations in myocardial metabolism, cardiomyocyte hypertrophy, cell death, and structure and composition of the extracellular matrix. Here, we focus on the last of these and review current research demonstrating an important role for adipokines, with particular emphasis on leptin and adiponectin, in regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and collagens. From this, it is clear that adipokines are capable of contributing to remodeling of the myocardial extracellular matrix, and the altered adipokine profiles observed in obese individuals may be important in the pathogenesis of heart failure. The feasibility of adipokine manipulation as a potential therapeutic treatment in preventing maladaptive cardiac remodeling is also discussed.

Topics: Adipokines; Adiponectin; Collagen; Cytokines; Extracellular Matrix; Heart Failure; Humans; Leptin; Matrix Metalloproteinases; Myocardium; Myocytes, Cardiac; Obesity; Ventricular Remodeling

Chronic heart failure (CHF) is an enormous medical and communal burden. The syndrome is common, carries a grim prognosis and severely impacts quality of life. Those patients who develop cardiac cachexia combat both important disability and a poor outlook. Muscle wasting is a critical component of cachexia. The pathophysiological determinants are numerous and some of them are common to other chronic severe illnesses. There is increasing awareness, however, that heart failure related myopathy is a distinct entity, characterized by specific functional, structural and morphologic changes and the involvement of several neurohormonal pathways, catabolic processes, a pro-inflammatory environment and increased oxidative stress. Although clear-cut evidence based solutions for the problem are not readily available, the modulating effects of regular exercise in CHF patients suggest that physical training should at least be incorporated in the essentially multi-disciplinary approach.

Topics: Animals; Cachexia; Catecholamines; Exercise; Ghrelin; Heart Failure; Humans; Inflammation; Leptin; Muscle, Skeletal; Neurosecretory Systems; Oxidative Stress; Physical Conditioning, Animal

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Topics: Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Ghrelin; Heart Failure; Humans; Hypertension; Leptin; Obesity; Peptide Hormones; Thrombosis

Topics: Animals; Apoptosis; Cachexia; Cytokines; Heart Failure; Humans; Interleukins; Leptin; Neurotransmitter Agents; Tumor Necrosis Factor-alpha

Topics: Adipose Tissue; Animals; Biomarkers; Body Weight; Cachexia; Heart Failure; Humans; Leptin; Proteins

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; 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Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; 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Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients.. Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke.. In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031).. High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Coronary Artery Disease; Death, Sudden, Cardiac; Fasting; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Stroke

Obese subjects have elevated leptin levels, which have been associated with increased risk of cardiovascular events. Because leptin has direct cellular effects on various tissues, we tested the hypothesis that leptin levels are associated with cardiac structure or function in patients with coronary artery disease (CAD).. The study population consisted of 1 601 CAD patients, of whom 42% had type 2 diabetes mellitus. Plasma leptin was measured in fasted state and an echocardiography performed. Leptin levels were not related to LV dimensions or LV ejection fraction (NS for all), but higher leptin levels were associated with elevated E/E' (9.43 vs. 11.94 in the lowest and the highest leptin quartile, respectively; p=0.018 for trend). Correspondingly, a decreasing trend was observed in E/A (1.15 vs. 1.06; p=0.037). These associations were independent of obesity and other relevant confounding variables.. We conclude that elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables. Leptin may be one of the mechanistic links explaining the development of congestive heart failure in obese subjects.

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diastole; Echocardiography; Female; Heart Failure; Humans; Leptin; Male; Middle Aged; Obesity; Risk Factors; Ventricular Dysfunction, Left

Chronic heart failure (CHF) is characterized by increased insulin resistance and hyperleptinaemia. We aimed to study effects of selective and non-selective beta-blockers on body weight, insulin resistance, plasma concentrations of leptin and resistin in patients with CHF.. Twenty-six non-cachectic beta-blocker-naive patients with CHF were randomized and treated with either carvedilol or bisoprolol. Body weight, plasma concentrations of leptin, resistin, fasting glucose and insulin were measured at baseline and after 6 months of therapy. Insulin resistance was estimated by homeostasis model assessment- estimated insulin resistance (HOMA-IR).. Body weight increased significantly in the carvedilol group (mean change + 2.30 kg, p = 0.023) while it did not change in the bisoprolol group (mean change -0.30 kg, p = 0.623) (ns between groups). Plasma leptin concentration increased only in the carvedilol group (mean change + 4.20 ng/ml, p = 0.019) (ns between groups). Fasting glucose and resistin remained unchanged in both groups. After 6 months, mean plasma insulin concentration changed significantly differently (p = 0.015) in the bisoprolol (mean change +3.1 microU/ml) compared to the carvedilol group (mean change -6.3 microU/ml) and HOMA-IR was consequently higher in the bisoprolol compared to the carvedilol group (5.2 +/- 4.2 vs 2.8 +/- 1.6, p = 0.046).. This study found different metabolic effects of carvedilol and bisoprolol in non-cachectic patients with CHF. With unchanged fasting plasma glucose concentration after 6 months of treatment, carvedilol significantly decreased plasma insulin concentration and insulin resistance compared to bisoprolol.

Topics: Adrenergic beta-Antagonists; Aged; Bisoprolol; Blood Glucose; Body Weight; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Propanolamines; Resistin

Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men.. In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p < 0.0001).. In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.

Topics: Biomarkers; Fatty Acid-Binding Proteins; Female; Heart Failure; Humans; Leptin; Lipids; Male; Matrix Metalloproteinases; Prognosis; Stroke Volume; Ventricular Function, Left

Leptin is an adipocyte-derived peptide involved in energy homeostasis and body weight regulation. The position of leptin in cardiovascular pathophysiology remains controversial. Some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as a neutral or even protective factor. We have explored whether high leptin affects the mortality and morbidity risk in patients with stable coronary heart disease.. We followed 975 patients ≥6 months after myocardial infarction or coronary revascularization in a prospective study. All-cause or cardiovascular death, non-fatal cardiovascular events (recurrent myocardial infarction, stroke, or any revascularization), and hospitalizations for heart failure (HF) we used as outcomes. High serum leptin concentrations (≥18.9 ng/mL, i.e., 4th quartile) were associated with worse survival, as well as with a higher incidence of fatal vascular events or hospitalizations for HF. Even after full adjustment for potential covariates, high leptin remained to be associated with a significantly increased 5-years risk of all-cause death [Hazard risk ratio (HRR) 2.10 (95%CIs:1.29-3.42), p < 0.003], CV death [HRR 2.65 (95%CIs:1.48-4.74), p < 0.001], and HF hospitalization [HRR 1.95 (95% CIs:1.11-3.44), p < 0.020]. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced [HRR 1.27 (95%CIs:0.76-2.13), p = 0.359].. High leptin concentration entails an increased risk of mortality, apparently driven by fatal CV events and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.

Topics: Coronary Artery Disease; Heart Failure; Humans; Leptin; Myocardial Infarction; Prospective Studies; Risk Factors

Background Frailty is a multifactorial physiological syndrome most often associated with age but which has received increasing recognition as a component of chronic illnesses such as heart failure. Patients with heart failure are likely to be frail, irrespective of their age. Adipokine dysregulation, which is associated with frailty, occurs in patients with heart failure. In this study, we tested the hypothesis that adipokines are associated with frailty in patients with heart failure. Methods Thirty-five patients with heart failure (age, 67 ± 14 years; 25 males; left ventricular ejection fraction, 45 ± 19%) were included. Serum adipokine levels, physical performance, and body composition were measured. Results Adiponectin and leptin were inversely correlated with grip strength. Adiponectin was inversely correlated with bone mineral density. Leptin was positively correlated with fat mass. Adipokines were not correlated with skeletal muscle mass. Conclusions Adipokines were associated with frailty in patients with heart failure. Adipokine dysregulation may play a role in the development of frailty in heart failure.

Topics: Adipokines; Aged; Aged, 80 and over; Female; Frailty; Heart Failure; Humans; Leptin; Male; Middle Aged; Stroke Volume; Ventricular Function, Left

Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited.. To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF.. This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019.. Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing.. Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001)).. Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.

Topics: Adipokines; Adiponectin; Aged; C-Reactive Protein; Cardiometabolic Risk Factors; Diabetes Mellitus; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Hypertension; Insulin Resistance; Interleukin-6; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Obesity; Oxygen Consumption; Pulmonary Gas Exchange; Sex Factors; Stroke Volume

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

To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM).. This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories.. LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum.. Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (. Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

Topics: Adult; Body Mass Index; Cardiomyopathies; Female; Heart Failure; Humans; Leptin; Obesity, Maternal; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Topics: Female; Heart Failure; Humans; Hypertrophy, Left Ventricular; Leptin; Molecular Epidemiology; Obesity; Stroke Volume

Introduction: Over the years, heart failure remains one of the most common and prognostically unfavorable conditions. The aim of our study was to determine the frequency of complications in patients with CHF depending on the body weight and intoxication syndrome of varying degrees of severity.. Materials and methods: A complete clinical examination was performed in 58 patients (41 (70.6%) men and 17 (29.4%) women) with CHF. In addition to the standard examination in accordance with the protocol, the level of endogenous intoxication was determined by the level of medium-weight molecules (MWM254) and leptin. The patients were randomized into 4 groups depending on their body mass index and the degree of endogenous intoxication. Statistical processing of the results was carried out using the methods of variation statistics "Statistica 6.0".. Results: It was revealed that the worst survival rate is observed in patients with normal body mass against the background of the expressed endogenous intoxication syndrome, the best survival rate is observed provided that there are a normal body mass and endogenous intoxication of a minimum degree. An inverse correlation between the body mass index and the endogenous intoxication indicator (blood MWM) was detected. Patients with CHF should have their leptin level evaluated. An increase in its level was associated with arterial hypertension, an increase in blood glucose levels and lipid metabolism disorders.. Conclusions: Increased level of blood MWM worsens the forecast of CHF. The unfavorable outcome was observed in patients with the combination of hypoleptinemia with severe endogenous intoxication.

Topics: Body Mass Index; Body Weight; Chronic Disease; Female; Heart Failure; Humans; Leptin; Male; Prognosis

Low leptin concentration has been shown to be associated with central sleep apnea in heart failure patients. We hypothesized that low leptin concentration predicts central sleep apnea. Consecutive ambulatory New York Heart Association (NYHA) classes I-IV heart failure patients were studied prospectively, including measurement of serum leptin, echocardiography and polysomnography. Sleep apnea was defined by type (central/mixed/obstructive) and by apnea-hypopnea index ≥5 by polysomnography. Subjects were divided into four groups by polysomnography: (1) central sleep apnea, (2) mixed apnea, (3) no apnea and (4) obstructive sleep apnea. Fifty-six subjects were included. Eighteen subjects were diagnosed with central sleep apnea, 15 with mixed apnea, 12 with obstructive apnea and 11 with no sleep apnea. Leptin concentration was significantly lower in central sleep apnea compared to obstructive apnea (8 ± 10.7 ng mL

Topics: Aged; Biomarkers; Female; Heart Failure; Humans; Leptin; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Central

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Evidence-Based Medicine; Heart; Heart Failure; Humans; Hypoglycemic Agents; Leptin; Myocardium; Obesity; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission.

Topics: Aged; Circadian Rhythm; Critical Illness; Female; Heart Failure; Humans; Leptin; Male; Middle Aged

Heart transplant (HTx) and left ventricular assist device (LVAD) implant are the best options for symptomatic end stage heart failure, but LVAD patients show lower rehabilitative outcome than HTx patients. To investigate the causes, we compared biomarkers levels and their association with rehabilitative outcome in 51 HTx and in 46 LVAD patients entering the same cardiac rehabilitation program. In both groups, routine biomarkers were measured at start (T1) and end (T2) of cardiac rehabilitation while homocysteine, leptine and IGF-1 were measured at T1 only. HTx patients had lower lymphocyte, platelets, glucose, total proteins and albumin at T1; differences with LVAD patients vanished during rehabilitation when new cases of diabetes were observed in HTx. By contrast, total cholesterol, LDL and HDL fractions, leptin and IGF-1 were higher in HTx patients. The increase from T1 to T2 in six-minute walking test distance, measure of functional rehabilitation outcome, was positively associated with homocysteine and IGF-1 levels in HTx patients. In conclusion, during rehabilitation care should be paid to the early occurrence of dyslipidemia and hyperglycemia in HTx patients, which also require a proper protein dietary support. IGF-1, dangerously low in LVAD patients, might contribute to their lower rehabilitative outcome.

Topics: Adult; Aged; Bilirubin; Biomarkers; Cardiac Rehabilitation; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Homocysteine; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged

Heart failure with reduced ejection fraction (HFrEF) exhibits a "reverse metabolic profile". Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.. In patients with HFpEF(n=79), HFrEF(n=84), and controls(n=71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.. Leptin levels in HFpEF and HFrEF were increased (p<0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL.There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r=-0.364 p=0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p=0.044) but not in HFpEF. Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) μg/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p=0.310 but, compared to controls, higher levels in HFpEF (p=0.044) and HFrEF (p=0.001). Adiponectin correlated positively with NT-proBNP; r=0.396 p<0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p=0.045).. HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.

Topics: Adiponectin; Aged; Biomarkers; Case-Control Studies; Female; Heart Failure; Humans; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Stroke Volume

Topics: Atrial Natriuretic Factor; Female; Heart Failure; Humans; Leptin; Male; Natriuretic Peptide, Brain; Sleep Apnea, Central

Topics: Atrial Natriuretic Factor; Female; Heart Failure; Humans; Leptin; Male; Natriuretic Peptide, Brain; Sleep Apnea, Central

Topics: Adrenergic beta-Agonists; Animals; Female; Heart; Heart Failure; Isolated Heart Preparation; Isoproterenol; Lactation; Leptin; Pregnancy; Rats; Rats, Wistar; Sympathetic Nervous System

Leptin-deficient animals hyperventilate. Leptin expression by adipocytes is attenuated by atrial natriuretic peptide (ANP). Increased circulating natriuretic peptides (NPs) are associated with an increased risk of central sleep apnea (CSA). This study tested whether serum leptin concentration is inversely correlated to NP concentration and decreased in patients with heart failure (HF) and CSA.. Subjects with HF (N = 29) were studied by measuring leptin, NPs, CO2 chemosensitivity (Δminute ventilation [V.e]/Δpartial pressure of end-tidal CO2 [Petco2]), and ventilatory efficiency (V.e/CO2 output [V.co2]) and were classified as CSA or no sleep-disordered breathing by polysomnography. CSA was defined as a central apnea-hypopnea index ≥ 15. The Student t test, Mann-Whitney U test, and logistic regression were used for analysis, and data were summarized as mean ± SD; P < .05 was considered significant.. Subjects with CSA had higher ANP and brain natriuretic peptide (BNP) concentrations (P < .05), ΔV.e/ΔPetco2 (2.39 ± 1.03 L/min/mm Hg vs 1.54 ± 0.35 L/min/mm Hg, P = .01), and V.e/V.co2 (43 ± 9 vs 34 ± 7, P < .01) and lower leptin concentrations (8 ± 10.7 ng/mL vs 17.1 ± 8.8 ng/mL, P < .01). Logistic regression analysis (adjusted for age, sex, and BMI) demonstrated leptin (OR = 0.07; 95% CI, 0.01-0.71; P = .04) and BNP (OR = 4.45; 95% CI, 1.1-17.9; P = .05) to be independently associated with CSA.. In patients with HF and CSA, leptin concentration is low and is inversely related to NP concentration. Counterregulatory interactions of leptin and NP may be important in ventilatory control in HF.

Topics: Aged; Ambulatory Care Facilities; Atrial Natriuretic Factor; Case-Control Studies; Female; Heart Failure; Humans; Leptin; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Polysomnography; Sleep Apnea, Central

We have investigated the role of muscle mass, natriuretic peptides and adipokines in explaining the obesity paradox.. The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease (CHD) or heart failure (HF).. Prospective study of 4046 men aged 60-79 years followed up for a mean period of 11 years, during which 1340 deaths occurred. The men were divided according to the presence of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii) with HF.. Overweight (BMI 25-9.9 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) were associated with lower mortality risk compared to men with normal weight (BMI 18.5-24.9 kg/m(2)) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and 0.77 (0.57,1.04); p=0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and 0.41 (0.16,1.09; p=0.04 for trend). Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01) and 0.96 (0.68,1.36) p=0.60 for trend) but made minor differences to those with HF [p=0.05]. Leptin related positively to mortality in men without HF but inversely to mortality in those with HF; adjustment for leptin abolished the BMI mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71); p=0.98 for trend].. The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass. In men with HF, leptin (possibly reflecting cachexia) explain the inverse association.

Topics: Aged; Biomarkers; Body Mass Index; Body Weight; Coronary Disease; Follow-Up Studies; Heart Failure; Humans; Leptin; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Obesity; Prospective Studies; Survival Rate

Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated.. 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months.. Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p < 0.0001), while obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p < 0.0001) and leptin (38.4 ± 21.2 vs 76.28 ± 17.48 ng/ml, p < 0.0001) values were lower. At ROC analyses the diagnostic profile of ghrelin (AUC 0.962; sensitivity 83%; specificity 98%), obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 - 1.03; p < 0.0001) and leptin (HR 0.94; 95% CI 0.92 - 0.96; p < 0.0001) were significant predictors of death even after correction for other known risk factors such as presence of metastasis and chronic kidney disease.. Ghrelin and leptin are promising biomarkers to diagnose cachexia and to predict survival in cancer patients.

Topics: Aged; Area Under Curve; Biomarkers; Cachexia; Case-Control Studies; Cholesterol; Diabetes Mellitus; Female; Follow-Up Studies; Ghrelin; Heart Failure; Humans; Kaplan-Meier Estimate; Leptin; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Predictive Value of Tests; Proportional Hazards Models; ROC Curve; Serum Albumin; Survival Rate

Increased serum leptin concentration has been linked to increased ventilation in patients with mild heart failure (HF). However, in animal models the absence of leptin has also been associated with increased ventilation. This study evaluated the relationship of circulating leptin concentration with exercise ventilation in HF patients.. Fifty-eight consecutive ambulatory HF patients were stratified by quintiles of leptin concentration, with a lowest quintile of mean leptin concentration of 1.8 ± 8.9 ng/mL and a highest of 33.3 ± 30.3 ng/mL. Peak exercise ventilatory efficiency (VE/VCO2) was significantly elevated in the lowest (46 ± 6 vs 34 ± 4; P < .01) as well as in the highest (38 ± 8 vs 34 ± 4; P < .05) leptin concentration quintiles compared with the reference middle quintile. Multiple regression analysis adjusted for confounders such as age, sex, and body mass index showed leptin concentration to be independently inversely correlated to VE/VCO2 in the low-to-normal quintiles (β = -0.64; P < .01), positively in the normal-to-high quintiles (β = 0.52; P = .02), and positively correlated to PETCO2 in the low-to-normal quintiles (β = 0.59; P = .01) and inversely in the normal-to-high quintiles (β = -0.53; P = .02).. In HF patients, both high and low leptin concentrations are associated with increased VE/VCO2 and decreased PETCO2 with a nonlinear U-shaped relationship, suggesting that either leptin deficiency or leptin resistance may modulate ventilatory control in HF patients.

Topics: Aged; Biomarkers; Exercise Test; Female; Heart Failure; Humans; Leptin; Male; Middle Aged; Pulmonary Ventilation; Stroke Volume

The relationship between echocardiographically measured epicardial fat thickness (EFT) and plasma concentrations of leptin, ghrelin, and adiponectin has not been evaluated in patients with noncachectic heart failure (HF). Patients with noncachectic HF and age- and sex-matched controls did not differ significantly in EFT, whereas EFT values showed significant positive correlation with body mass index (BMI) in both groups and were negatively related with brain natriuretic peptide and positively with log leptin values in the HF group. In the control group, a positive correlation with high-sensitivity C-reactive protein (hsCRP) and a negative correlation with log ghrelin were found. In multivariable analysis, log leptin was a significant predictor of EFT in patients with HF, but this effect was not retained after adjusting for BMI. In contrast, log ghrelin and hsCRP were significant predictors of EFT in controls even after adjusting for BMI.

Topics: Adipose Tissue; Adiposity; Aged; Aged, 80 and over; Body Mass Index; Body Weight; C-Reactive Protein; Female; Ghrelin; Heart Failure; Homeostasis; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Pericardium; Ultrasonography

Topics: Adipose Tissue; Female; Ghrelin; Heart Failure; Humans; Leptin; Male; Pericardium

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Chi-Square Distribution; Echocardiography, Doppler; Egypt; Female; Gene Frequency; Genetic Predisposition to Disease; Heart Failure; Humans; Leptin; Lipids; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Genetic; Receptors, Leptin; Regression Analysis; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

β3-Adrenergic receptors (β3ARs) negatively regulate β-adrenergic signaling via nitric oxide and are dependent on the adipokine leptin for normal expression in adipocytes, thus making β3AR an attractive candidate for cross-talk with leptin in the heart. Accordingly, we tested the hypothesis that cardiac β3AR expression and function are dependent on leptin and are severely diminished in leptin-deficient ob/ob mice. Using isolated cardiac myocyte physiology studies, we found that β3AR function was significantly diminished in ob/ob myocytes and in wild-type myocytes treated with leptin antagonist. This finding was supported by quantitative PCR demonstrating markedly decreased β3AR mRNA levels in ob/ob mice. Both β3AR mRNA and function were restored in ob/ob mice after in vivo leptin repletion. We propose that diminished β3AR signaling may be the critical element to explain the direct effects of leptin on the myocardium and suggest that this work reveals a key feature in the role of leptin in obesity-related cardiac hypertrophy and heart failure.

Topics: Adrenergic beta-Agonists; Animals; Heart Failure; Leptin; Mice; Mice, Inbred Strains; Mice, Obese; Myocytes, Cardiac; Obesity; Polymerase Chain Reaction; Receptors, Adrenergic, beta-3; Receptors, Leptin; RNA, Messenger; Signal Transduction

Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF.. Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 6.4±2.1 μg/mL, P=0.02). VAD implantation (mean, 129±99 days) reduced serum adiponectin (7.4±3.4 μg/mL, P<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 7.6±7.7-4.5±3.6; P=0.012). [corrected] Adiponectin expression in adipose tissue decreased after VAD implantation (-65%; P<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (2105±585 μm(2) [corrected] versus 5583±142 μm(2) in control subjects; P<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%; P<0.01), which normalized after VAD implantation.. Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation, and adiponectin resistance in patients with advanced HF.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Macrophages; Male; Middle Aged; Resistin; Retrospective Studies; Severity of Illness Index; Signal Transduction

The expression of leptin and resistin is known to be positively correlated with the incidence of chronic heart failure (CHF). Both adipokines have been implicated in immunomodulation and cardiac remodelling. Therefore, we performed for the first time a clinical study to elucidate the effects of leptin and resistin on progression of CHF in patients with non-ischaemic dilated (DCM) and inflammatory (DCMi) cardiomyopathy.. For the clinical study 120 patients were divided into a control (n = 16), DCM (n = 52), and DCMi (n = 52) group to determine the effect of leptin and resistin on CHF progression. Nuclear factor-κB (NF-κB) activation, reactive oxygen species generation, and tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression following adipokine exposition were determined in vitro in cardiomyocytes. Leptin and resistin systemic plasma levels and not cardiac expression were significantly elevated in patients with DCM (leptin, 13.12 ± 17.2 ng/mL, P < 0.05; resistin, 6.87 ± 2.25 ng/mL, P < 0.05) and DCMi (leptin, 13.63 ± 16 ng/mL, P < 0.05; resistin, 7.27 ± 2.2 ng/mL, P < 0.05) compared with the control group (leptin, 7.34 ± 5.7 ng/mL; resistin, 4.4 ± 1.18 ng/mL). A multivariate linear regression model revealed low leptin and resistin plasma levels as contributors for favourable cardiac functional parameters at 6-month follow-up independent of inflammatory conditions. Cell culture experiments in vitro showed leptin and resistin to be potent regulators of TNF-α and IL-6 expression in cardiomyocytes, leading to significantly increased redox stress in cardiac cells.. High leptin and resistin expression in patients with DCM and DCMi is associated with CHF progression, i.e. severe cardiac dysfunction, independent of immune responses.

Topics: Adult; Biomarkers; Cardiomyopathies; Disease Progression; Female; Health Status Indicators; Heart Failure; Hemodynamics; Humans; Inflammation; Leptin; Male; Middle Aged; Multivariate Analysis; Prognosis; Resistin; ROC Curve; Statistics as Topic; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

We examined the relationship between body mass index (BMI), waist circumference, and incident HF in men with and without pre-existing coronary heart disease (CHD) and assessed the contribution of plasma leptin concentration to these associations.. Leptin has been proposed as a potential link between obesity and heart failure (HF).. This was a prospective study of 4,080 men age 60 to 79 years with no diagnosed HF followed for a mean period of 9 years, in whom there were 228 incident HF cases.. Increased BMI was associated with significantly increased risk of HF in men with and without pre-existing CHD (myocardial infarction or angina) after adjustment for cardiovascular risk factors including C-reactive protein. The adjusted hazard ratios (HRs) associated with a 1-SD increase in BMI were 1.37 (95% confidence interval [CI]: 1.09 to 1.72) and 1.18 (95% CI: 1.00 to 1.39) in men with and without CHD, respectively. Increased leptin was significantly associated with an increased risk of HF in men without pre-existing CHD, independent of BMI and potential mediators (adjusted HR for a 1-SD increase in log leptin: 1.30 [95% CI: 1.06 to 1.61]; p = 0.01). However, no association was seen in those with pre-existing CHD (corresponding HR: 1.06 [95% CI: 0.77 to 1.45]; p = 0.72). Adjustment for leptin abolished the association between BMI and HF in men with no CHD; in those with CHD, the association between BMI and HF remained significant (p = 0.03). Similar patterns were seen for waist circumference.. In the absence of established CHD, the association between obesity and HF may be mediated by plasma leptin. In those with CHD, obesity appears to increase the risk of HF independent of leptin.

Topics: Aged; Body Mass Index; Comorbidity; Coronary Disease; Heart Failure; Humans; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Risk Factors; Waist Circumference

Topics: Coronary Disease; Heart Failure; Humans; Leptin; Male; Obesity

Ghrelin has effects on appetite and growth. Recent reports suggest effects on cardiac function, but no study has evaluated the ghrelin levels of congenital heart disease (CHD) infants with heart failure. The purpose of the present study was therefore to investigate the relationship between ghrelin level and growth and cardiac function in CHD infants.. Twenty-eight infants with CHD were eligible for the study. Blood samples were obtained at the time of insertion of intracardiac catheter and correlation was examined between ghrelin plasma level and anthropometric parameters, including z score of height and weight, body mass index (BMI), and %bodyweight gain rate, severity of heart failure, and the levels of leptin and insulin-like growth factor-1.. In the CHD group, active ghrelin (A-Ghr) had a significant negative correlation with z score of bodyweight, and a significant positive correlation with cardiac function. There were no correlations, however, with height and BMI. A-Ghr levels were significantly higher in the high heart failure index score group. Significant correlation between A-Ghr and desacyl-ghrelin in the CHD group was observed.. A-Ghr is involved in cardiac function and has little effect on their physique in infants with CHD.

Topics: Anthropometry; Biomarkers; Body Height; Body Weight; Case-Control Studies; Child Development; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Growth; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Humans; Infant; Infant, Newborn; Japan; Leptin; Male; Reference Values; Risk Assessment; Somatomedins; Statistics, Nonparametric

Topics: Absorptiometry, Photon; Adipocytes; Adipokines; Adult; Analysis of Variance; Area Under Curve; Body Composition; Body Weight; Case-Control Studies; Cross-Sectional Studies; Female; Heart Failure; Heart Transplantation; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity, Abdominal; Oxygen Consumption; Statistics as Topic

The aim of the study was to investigate the associations of adiponectin and leptin to bone mass and bone specific surrogates in elderly males with chronic heart failure (CHF).. Seventy-three males (mean age 68 +/- 7 years) with stable mild to moderate CHF and 20 healthy individuals age- and body mass index-matching underwent dual energy x-ray absorptiometry measurements (bone mineral density (BMD) at hip and lumbar spine, total bone mineral content, and body composition); echocardiography; 6-minute walk test; grip strength; and biochemical assessment including adiponectin, leptin, bone specific surrogates (osteocalcin, beta-CrossLaps, osteoprotegerin [OPG], receptor activator of nuclear factor kappaB ligand [RANKL]), parathyroid hormone, 25-hydroxy vitamin D, testosterone, sex hormone-binding globulin, and NT-pro-BNP. Serum adiponectin, osteocalcin, beta-CrossLaps, OPG, RANKL, and parathyroid hormone were significantly increased in CHF patients, whereas 25-hydroxy vitamin D was significantly lower compared to healthy controls. The significant positive association was found between adiponectin level with osteocalcin, beta-CrossLaps, OPG, and RANKL among CHF patients. In multivariate regression analysis, adiponectin was a significant determinant of total hip BMD, although the variance was small (r(2) = 0.239), whereas leptin was determinant for total bone mineral content (r(2) = 0.469) in patients with CHF.. Serum adiponectin is an independent predictor of BMD in elderly males with mild to moderate CHF, and showed a positive correlation to bone specific surrogates. Adiponectin, as cardioprotective hormone, seems to be able to exert a negative effect on bone mass in chronic heart failure. Further research is needed to confirm the potential for adipokines in the crosstalk between bone and energy metabolism in CHF patients.

Topics: Adiponectin; Aged; Biomarkers; Bone and Bones; Bone Density; Chronic Disease; Heart Failure; Humans; Leptin; Lumbar Vertebrae; Male; Middle Aged; Predictive Value of Tests; Radiography

Topics: Heart Failure; Humans; Leptin; Oxidative Stress

There is an increasing interest in the role of leptin in cardiovascular pathophysiology, including proinflammatory effects. Many studies have reported elevated leptin levels in non-cachectic patients with chronic heart failure (CHF), however, the role of leptin in CHF remains unclear.. To assess the relationship between leptin levels in patients with CHF and left ventricular (LV) systolic dysfunction in relation to ventilatory response to exercise and hsCRP levels.. The study group consisted of 41 patients (mean age 50.2 ± 9.3 years) with stable CHF and LV ejection fraction < 45% and eight healthy controls (mean age 43.6 ± 14.7 years). Sixteen (39%) patients had coronary artery disease. All subjects underwent anthropometric measurements (weight, height, and waist circumference), standard echocardiography, and maximal cardiopulmonary exercise treadmill test. Biochemical analysis included the assessment of leptin and hsCRP levels as well as white blood count (WBC) and erythrocyte sedimention rate.. Leptin levels, including body mass index (BMI)-adjusted leptin levels, were significantly higher in the CHF patients than in the controls (9.2 ± 7.5 vs 2.9 ± 1.25 ng/mL; p = 0.005). We found significantly higher WBC, neutrophil count, lymphocyte percentage and BNP levels in the CHF group vs controls. There were significant correlations in the CHF group between leptin levels and BMI (r = 0.55; p < 0.05), waist circumference (r = 0.49; p < 0.05), leukocyte count (r = 0.41; p < 0.05), hsCRP levels (r = 0.34; p < 0.05), and peak VO₂ (r = -0.34; p < 0.05). Multivariate step forward regression analysis showed that peak VO₂ was significantly related with leptin levels. After adding VE/VCO₂ slope to the multivariate regression analysis model, only VE/VCO₂ slope was independently associated with leptin levels.. There is a significant relationship between serum leptin levels and peak VO₂, VE/VCO₂ slope and levels of inflammatory markers in patients with CHF.

Topics: Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Heart Failure; Humans; Inflammation; Leptin; Male; Middle Aged; Ventricular Dysfunction, Left

Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals.. We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed.. Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels.. In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.

Topics: Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Female; Heart Failure; Humans; Incidence; Leptin; Male; Massachusetts; Obesity; Regression Analysis; Risk Factors

The purpose of this study was to establish the prevalence of insulin resistance (IR) among nondiabetic chronic heart failure (CHF) patients and to seek factors associated with IR in CHF, including the relationship of IR to functional class, exercise capacity, and disease severity in CHF.. Several lines of evidence suggest that CHF is an IR state. The prevalence of IR in CHF and its relation to CHF have not been fully defined.. Fasting insulin resistance index (FIRI) was assessed in a cohort of 129 consecutive CHF patients (mean age 69.2 +/- 10.4 years; 76% males; body mass index 27.4 +/- 4.4 kg/m(2)). Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT).. Prevalence of IR as defined by FIRI > or =2.7 was 61% in our cohort of CHF patients. There was a significant correlation between IR and waist circumference (r = 0.37; p < 0.01), serum triglycerides (r = 0.34; p < 0.01), high-density lipoprotein cholesterol (r = -0.22; p = 0.02), and serum leptin (r = 0.39; p = 0.03). Insulin resistance increased significantly with worsening New York Heart Association functional class (p < 0.01). The CHF patients with IR had a significantly lower exercise capacity and peak oxygen consumption than patients with an FIRI <2.7. The RH-PAT ratio was significantly lower in CHF patients with IR compared with CHF patients with an FIRI <2.7 (1.6 +/- 0.3 vs. 2.0 +/- 0.5; p < 0.05).. Insulin resistance is highly prevalent among nondiabetic CHF patients and is associated with decreased exercise capacity in patients with CHF. (Insulin Resistance: Heart Failure; NCT00486967).

Topics: Cholesterol, HDL; Cohort Studies; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Insulin Resistance; Leptin; Logistic Models; Male; Oxygen Consumption; Prevalence; Triglycerides; United States

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chronic Disease; Czech Republic; Female; Gene Frequency; Genetic Predisposition to Disease; Heart Failure; Humans; Leptin; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Pro-Opiomelanocortin; Receptors, Leptin; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Ventricular Function, Left; White People; Young Adult

Topics: Adipokines; Adiponectin; Animals; Heart Failure; Humans; Leptin; Obesity; Risk Factors

Cardiac injury induced by isoprenaline produces stress. This stress can be mediated by the activated endothelin and leptin pathway; thus, the endothelin receptor antagonist CPU0213 may reverse these changes. CPU0213 is metabolized mainly by cytochrome P450 (CYP)3A, thus, erythromycin, an inhibitor of CYP3A, could affect its effects by raising its plasma levels.. Forty rats were divided into five groups. Group 1 rats were normal. Group 2 rats were administered isoprenaline (1 mg/kg, s.c.) for 10 days. Groups 3, 4 and 5 were administered isoprenaline, but group 3 was given erythromycin (100 mg/kg, p.o.) alone on days six to ten, group 4 was given CPU0213 20 mg/kg (s.c.) on days six to ten, whilst group 5 received erythromycin plus CPU0213 on days six to ten. Measurements were conducted to observe changes in the haemodynamics, cardiac weight index, serum lactate dehydrogenase and creatine kinase levels, and expression of endothelin receptor A (ETA), leptin and its OBRb receptor.. In isoprenaline-treated rats, cardiac hypertrophy and dysfunction were found. This was associated with upregulated myocardial leptin protein and OBRb receptor mRNA. Immunohistochemical assay of ETA was upregulated, accompanied with downregulation of FKBP12.6 (calstabin 2) in isoprenaline-treated rats. These effects were significantly reversed by CPU0213. HPLC assay presented an increased plasma level of CPU0213 by erythromycin, but no change in its effects.. CPU0213 improved isoprenaline-induced cardiomyopathy by modulating ETA, leptin and FKBP12.6. However, erythromycin increased plasma levels but did not change its effects.

Topics: Animals; Cardiomegaly; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Down-Regulation; Endothelin Receptor Antagonists; Erythromycin; Heart Failure; Hemodynamics; Isoproterenol; Leptin; Male; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Reverse Transcriptase Polymerase Chain Reaction; Tacrolimus Binding Proteins; Up-Regulation

A high-fat diet can increase adiposity, leptin secretion, and plasma fatty acid concentration. In hypertension, this scenario may accelerate cardiac hypertrophy and development of heart failure but could be protective by activating peroxisome proliferator-activated receptors and expression of mitochondrial oxidative enzymes. We assessed the effects of a high-fat diet on the development of left ventricular hypertrophy, remodeling, contractile dysfunction, and the activity of mitochondrial oxidative enzymes. Mice (n = 10-12/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either a low-fat diet (10% of energy intake as fat) or a high-fat diet (45% fat) for 6 wk. The high-fat diet increased adipose tissue mass and plasma leptin and insulin. Left ventricular mass and chamber size were unaffected by diet in sham animals. TAC increased left ventricular mass (approximately 70%) and end-systolic and end-diastolic areas (approximately 100% and approximately 45%, respectively) to the same extent in both dietary groups. The high-fat diet increased plasma free fatty acid concentration and prevented the decline in the activity of the mitochondrial enzymes medium chain acyl-coenzyme A dehydrogenase (MCAD) and citrate synthase that was observed with TAC animals on a low-fat diet. In conclusion, a high-fat diet did not worsen cardiac hypertrophy or left ventricular chamber enlargement despite increases in fat mass and insulin and leptin concentrations. Furthermore, a high-fat diet preserved MCAD and citrate synthase activities during pressure overload, suggesting that it may help maintain mitochondrial oxidative capacity in failing myocardium.

Topics: Acyl-CoA Dehydrogenase; Adiposity; Animals; Biomarkers; Blood Glucose; C-Reactive Protein; Citrate (si)-Synthase; Dietary Fats; Disease Models, Animal; Disease Progression; Fatty Acids, Nonesterified; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Inflammation Mediators; Insulin; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mitochondria, Heart; Mitochondria, Muscle; Muscle, Skeletal; Myocardial Contraction; Myocardium; Oxidation-Reduction; RNA, Messenger; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Increased circulating leptin is present in human heart failure, and leptin deficiency is linked to worse outcomes in chronic ischemic injury. In the present observational study, we tested the hypothesis that cardiac leptin production and signaling are increased in the failing human heart, and that mechanical unloading with a ventricular assist device (VAD) reverses these changes.. All studies were performed using human cardiac tissue obtained from (1) hearts not matched for transplantation (nonfailing), (2) at the time of cardiac transplant (failing), or (3) paired samples at the time of VAD implant (pre-VAD) and removal (post-VAD). The expression of brain naturetic peptide, leptin, leptin receptor, and tumor necrosis factor alpha mRNA was measured, and the protein expression of leptin and its receptor was examined by Western blot and immunofluorescent staining of cardiac sections. The assessment of leptin signaling was performed by measuring the phosphorylation state of the leptin receptor. The phosphorylation state of signal transducer and activator of transcription-3 and AMP-activated kinase proteins were also measured. All data are expressed as mean+/-SEM with a statistical significance in failing relative to nonfailing groups determined by Student independent t test, and the significance between pre- and post-VAD groups determined by paired t test. In failing human hearts, the mRNA expressions of leptin and its receptor were increased 5.4+/-0.3-fold (P<0.05) and 4.5+/-0.3-fold (P<0.05), respectively, with similar changes in protein. The phosphorylation state of both the leptin receptor and signal transducer and activator of transcription-3 proteins were increased 1.4+/-0.1-fold (P<0.05), and the level of phosphorylated AMP-activated kinase protein was increased 1.9+/-0.2-fold (P<0.05). Mechanical unloading of the failing human heart with a VAD resulted in no change in tumor necrosis factor alpha expression but a marked decrease in leptin production to 1.7+/-0.1% (P<0.05) and leptin receptor expression to 3.0+/-0.2% (P<0.05) of pre-VAD levels. Phosphorylation of the leptin receptor, signal transducer and activator of transcription-3, and AMP-activated kinase were also decreased to 45+/-7%, 75+/-8%, and 58+/-8% of pre-VAD values, respectively (P<0.05 for all values).. These results indicate that the failing human heart increases expression of leptin and its receptor and that mechanical unloading downregulates this increase. Further, a cardioprotective role for leptin in the failing human heart is suggested through the activation of signal transducer and activator of transcription-3 and AMP-activated kinase signaling.

Topics: AMP-Activated Protein Kinases; Female; Heart Failure; Heart-Assist Devices; Humans; Leptin; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Phosphorylation; Receptors, Leptin; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Stroke Volume; Treatment Outcome; Tumor Necrosis Factor-alpha; Up-Regulation; Ventricular Function, Left

The interaction of salt sensitivity and obesity in development of cardiac hypertrophy is incompletely understood. The SHHF/Mcc-fa(cp) (SHHF) rat model was used to examine the effect of high salt on cardiac hypertrophy and expression of endothelin (ET) and nitric oxide synthase (NOS) isoforms. Homozygous lean (+/+) and obese (fa(cp)/fa(cp)) SHHF were fed a low-salt diet (0.3% NaCl) for seven days followed by a high-salt diet (8.0% NaCl) for seven days. To assess the role of ET in mediating cardiac hypertrophy and gene expression with high salt, additional groups were treated with an ET(A)/ET(B) receptor antagonist (bosentan) while on high salt. Obese SHHF showed an increase in systolic blood pressure and cardiac hypertrophy in response to the high-salt diet. High salt resulted in decreased expression of preproET as well as all three NOS isoforms in the Obese, while cytokine induced NOS (iNOS) and neuronal NOS (nNOS) increased in Leans. Though the salt-sensitive component of the hypertension observed in the Obese was prevented by bosentan, cardiac hypertrophy still occurred and expression of all NOS isoforms remained lower in Obese compared to Lean. Endothelial NOS (eNOS) expression increased in the Lean with bosentan. These studies suggest that cardiac hypertrophy is independent of the level of hypertension and may be mediated by altered production of NOS isoforms in salt-sensitive, obese SHHF.

Topics: Animals; Base Sequence; Blood Pressure; Bosentan; Cardiomegaly; DNA Primers; Endothelin Receptor Antagonists; Endothelins; Gene Expression; Heart Failure; Leptin; Male; Nitric Oxide Synthase; Obesity; Rats; RNA, Messenger; Sodium Chloride, Dietary; Sulfonamides

Leptin is elevated under conditions of both obesity and heart failure (HF), and activation of leptin receptor (ObR) signalling is known to increase in vivo cardiac contractility and to have anti-hypertrophic effects on the left ventricle (LV). However, it is unknown whether ObR signalling is altered in cardiomyocytes after myocardial infarction (MI) leading to HF, or if a deficiency in ObR signalling leads to worse HF.. In separate experimental protocols, C57BL/6J and leptin-deficient (ob/ob) mice underwent open-chest surgery to induce permanent left coronary artery ligation (CAL) or had a sham operation. Subgroups of ob/ob mice examined were lean (food-restricted), obese (food-ad libitum), and leptin repleted. Four weeks post-surgery, cardiac structure and function was examined by echocardiography, and the activation of cardiac leptin signalling was characterized through quantitative PCR, western blotting, and DNA-binding activities. CAL produced echocardiographic evidence of HF in C57BL/6J mice, elevated circulating leptin, increased cardiomyocyte leptin and ObR expression, and activated myocardial signal transducer and activator of transcription-3 (STAT3). In leptin-deficient ob/ob mice, whether lean or obese, CAL caused increased hypertrophy and dilation, decreased contractility of the LV, and worsened survival relative to wildtype or leptin-repleted mice after CAL. In ob/ob mice, activation of cardiac STAT3 signalling after CAL is enhanced in the presence of leptin and parallels the induction of the STAT3-responsive genes, tissue-inhibitor of metalloproteinase-1 and heat shock protein-70.. These data demonstrate that HF increases ObR signalling in cardiomyocytes and that activation of ObR signalling improves functional outcomes in chronic ischaemic injury leading to HF.

Topics: Animals; Cardiomegaly; Heart; Heart Failure; Leptin; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Ventricular Function, Left

Disruption of leptin signaling has been associated with both obesity and heart failure. We recently demonstrated that leptin deficiency in ob/ob mice and leptin insensitivity in db/db mice leads to increased myocyte apoptosis and left ventricular (LV) hypertrophy. We showed that LV mass, while similar among young ob/ob, db/db, and wild type (WT) mice, is significantly higher in old ob/ob and db/db versus WT. Ob/ob and db/db mice developed markedly increased rates of myocyte apoptosis by TUNEL and activated caspase-3 levels. An intriguing candidate for the study of obesity-associated cardiac hypertrophy and apoptosis is PI3K, which functions to not only regulate cell size but also maintain cell integrity through protection from apoptosis. Here we further show that ob/ob mice have decreased catalytic activity of phosphoinositide 3-kinase (PI3K) (p110alpha) which is reversed with leptin treatment. Leptin repletion in ob/ob mice also reduced both myocyte apoptosis and LV hypertrophy to WT levels. We have therefore concluded that normal leptin signaling is necessary to prevent age-related myocyte apoptosis and LV hypertrophy and that PI3K is a critical component of the leptin signaling axis. The decrease in p110alpha catalytic activity could explain the development of increased myocyte apoptosis and cardiac hypertrophy in these obese mouse models.

Topics: Animals; Apoptosis; Cardiomegaly; Caspase 3; Catalysis; Class I Phosphatidylinositol 3-Kinases; Heart Failure; Leptin; Mice; Mice, Obese; Muscle Cells; Myocardium; Phosphatidylinositol 3-Kinases

Heart failure is associated with decreased myocardial fatty acid oxidation capacity and has been likened to energy starvation. Increased fatty acid availability results in an induction of genes promoting fatty acid oxidation. The aim of the present study was to investigate possible mechanisms by which high fat feeding improved mitochondrial and contractile function in heart failure.. Male Wistar rats underwent coronary artery ligation (HF) or sham surgery and were immediately fed either a normal (14% kcal fat) (SHAM, HF) or high-fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for 8 weeks. Mitochondrial respiration and gene expression and enzyme activities of fatty acid-regulated mitochondrial genes and proteins were assessed. Subsarcolemmal (SSM) and interfibrillar mitochondria were isolated from the left ventricle. State 3 respiration using lipid substrates octanoylcarnitine and palmitoylcarnitine increased in the SSM of HF+FAT compared with SHAM+FAT and HF, respectively (242 +/- 21, 246 +/- 21 vs. 183 +/- 8, 181 +/- 6 and 193 +/- 17, 185 +/- 16 nAO min(-1) mg(-1)). Despite decreased medium-chain acyl-CoA dehydrogenase (MCAD) mRNA in HF and HF+FAT, MCAD protein was not altered, and MCAD activity increased in HF+FAT (HF, 65.1 +/- 2.7 vs. HF+FAT, 81.5 +/- 5.4 nmoles min(-1) mg(-1)). Activities of short- and long-chain acyl-CoA dehydrogenase also were elevated and correlated to increased state 3 respiration. This was associated with an improvement in myocardial contractility as assessed by left ventricular +dP/dt max.. Administration of a high-fat diet increased state 3 respiration and acyl-CoA dehydrogenase activities, but did not normalize mRNA or protein levels of acyl-CoA dehydrogenases in coronary artery ligation-induced heart failure rats.

Topics: Acyl-CoA Dehydrogenase; Adiponectin; Animals; Blood Glucose; Carnitine; Dietary Fats; Disease Models, Animal; Electron Transport Chain Complex Proteins; Fatty Acids, Nonesterified; Heart Failure; Insulin; Leptin; Male; Mitochondria, Heart; Myocardial Contraction; Rats; Rats, Wistar; Triglycerides

Leptin is a protein hormone produced by adipose tissue. Leptin has proinflammatory properties and is usually elevated in patients with chronic heart failure. We assessed if serum leptin relates to the loss in lung function in noncachectic patients with chronic heart failure.. One hundred thirty-five consecutively eligible non-Hispanic white subjects (age, 24 to 79 years; 85 men and 50 women) with a diagnosis of stable systolic heart failure were recruited prospectively, along with 106 matched control subjects. FVC, FEV(1), and single-breath diffusing capacity of the lung for carbon monoxide (DLco) were measured by spirometry. Plasma leptin was measured by radioimmunoassay. Multiple linear regression was applied.. The relationships of FEV(1), FVC, and DLco with leptin differed significantly between heart failure and control subjects after controlling for age, sex, percentage of body fat, and ejection fraction. In heart failure, leptin was as an independent predictor of FVC values (additional R(2) = 0.05, p < 0.0001), FEV(1) values (additional R(2) = 0.05, p < 0.0001), and DLco values (additional R(2) = 0.14, p < 0.0001). In a final multiple regression model predicting lung function in heart failure, the independent effect of leptin was significant after further adjustments.. The predictive information provided by leptin is additive to that provided by measures of body fat in heart failure patients, especially for DLco. Leptin may play a role in the impairment of lung function in subjects with heart failure.

Topics: Adult; Aged; Case-Control Studies; Female; Forced Expiratory Volume; Heart Failure; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Pulmonary Diffusing Capacity; Risk Factors; Vital Capacity

A number of investigators have observed insufficient 25-hydroxyvitamin D status in patients with congestive heart failure, suggesting a role for vitamin D insufficiency in the pathogenesis of this disorder. We have observed cardiac hypertrophy and collagen accumulation in rats deficient in vitamin D and in the hearts of vitamin D-receptor knockout mice. Our studies indicate that absence of vitamin D-mediated signal transduction and genomic activation results in cardiomyocytes overstimulation including increased contractility. These events ultimately lead to cardiomyocyte hypertrophy. In this report, we used spontaneously hypertensive heart failure rats cp/+ (hemyzygous for the corpulent gene, a mutant isoform of the leptin receptor) fed a normal and a high-salt diet to assess the potential for activated vitamin D (1,25 dihydroxyvitamin D3) to prevent cardiac hypertrophy and increases in cardiac output. After 13 weeks, as compared with untreated rats, we observed that 1,25 dihydroxyvitamin D3 treatment in rats fed a high-salt diet resulted in lower heart weight, myocardial collagen levels, left ventricular diameter, and cardiac output despite higher serum leptin levels. These studies suggest that 1,25(OH)2D3 treatment may prevent the development of cardiac hypertrophy, an important contributing factor in the progression of congestive heart failure.

Topics: Animals; Brain; Calcitriol; Calcium; Cardiac Output; Cardiomegaly; Collagen; Echocardiography; Female; Heart Failure; Hypertrophy, Left Ventricular; Leptin; Magnesium; Male; Mutation; Myocardium; Organ Size; Phosphates; Rats; Rats, Inbred SHR; Receptors, Leptin; Tibia; Vitamins

Heart failure (HF) may be produced by sustained beta-adrenoceptor stimulation by causing changes in the expression of endothelin-1 (ET-1), the leptin system, calcineurin and sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) underlying cardiac dysfunction. The aim of this study was to verify whether isoprenaline (ISO)-induced HF is attributed to changes in the above molecular markers, and whether the dual ET-receptor antagonist CPU0213 could reverse the cardiac dysfunction caused by ISO treatment, focusing on these molecular markers. HF was induced in rats by administration of ISO (2 mgkg(-1) s.c.) for 10 days. CPU0213 (30 mgkg(-1) s.c.) and propranolol (4 mgkg(-1) s.c.) were administered on days 7-10. HF developed after 10 days' ISO administration and was manifest as impaired cardiac performance, increased heart weight index, oxidative stress, elevated serum enzymes, and disordered expression of the endothelin system, leptin system, calcineurin and SERCA2a. All these abnormalities were significantly reversed by CPU0213, and the effectiveness of this ET-receptor antagonist was comparable to that of propranolol. Thus, antagonism of ET receptors by CPU0213 normalizes these changes in molecular markers, alleviating HF.

Topics: Animals; Calcineurin; Cardiotonic Agents; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Gene Expression Regulation; Heart Failure; Isoproterenol; Leptin; Male; Propranolol; Pyrazoles; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum Calcium-Transporting ATPases

The disease presentation of chronic heart failure (CHF) is considered to progress with metabolic deterioration, underlined by changes in adipose associated hormones (adipocytokines). However, little is known about ethnic variations of adipocytokines amongst CHF patients, in particular South Asians, who are at an increased risk of CHF.. Using a cross-sectional study, South Asians (n=106) and Caucasians (n=105) living in the UK were compared by CHF status. We investigated ethnic differences in adipocytokines (leptin, adiponectin, tumor necrosis factor (TNF)alpha), and their association with CHF. Patients with mild to moderate CHF were recruited from heart failure clinics (47 Caucasian, 54 South Asian), and compared to healthy controls. Metabolic parameters (including insulin resistance using HOMA modelling), echocardiography and brain natriuretic peptide (BNP) were measured amongst patients and healthy controls, and compared across and within ethnic groups.. Mean (log transformed) plasma leptin concentrations were highest amongst South Asian patients, being 5.25% (95%CI: 1.50-9.02) higher than Caucasian patients (P=0.007), and similarly raised with respect to controls (P< or =0.04). Indices of insulin resistance were higher amongst CHF patients compared with controls, with no ethnic variation. In addition to age, female gender and body-mass index, levels of leptin were also associated with South Asian ethnicity (P<0.001), insulin resistance (P=0.02), smoking habit (P=0.01) and HDL cholesterol (P=0.004). Levels of adiponectin showed no ethnic variation, but were associated with CHF and a previous history of myocardial infarction (P<0.001). On multivariate regression analysis of patients and healthy controls, CHF was independently associated with smoking habit, adiponectin and insulin resistance (all P<0.01).. Metabolic abnormalities are present in CHF, which in turn, are influenced by ethnicity. The role of adipocytokines in CHF pathophysiology and prognosis merits further study.

Topics: Adiponectin; Adult; Aged; Asia, Western; Asian People; Case-Control Studies; Chronic Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Insulin Resistance; Leptin; Male; Middle Aged; United Kingdom; White People

To demonstrate the hypothesis that dexamethasone (Dex) could improve chronic heart failure (CHF) by inhibiting the downstream signaling transduction of leptin but had no influence on the upregulation of leptin and its receptor in myocardium.. CHF was induced by left coronary artery ligation for 6 weeks. CHF rats were treated with Dex 50 mg.kg/d. Hemodynamics, histology, reactive oxygen species (ROS)-related parameters, and leptin concentrations in serum were measured. The mRNA expression of matrix metalloproteinases (MMP)2/9, tissue inhibitor of metalloproteinases (TIMP)1/2, tumor necrosis factor (TNF)-alpha, and OB-Rb were measured by RT-PCR.. In the CHF rats, hemodynamic functions were deteriorated, which was accompanied with myocardium remodeling and histological changes. CHF rats showed hyperleptinemia and excessive ROS in the serum, and the upregulation of MMP-2/9, TNF-alpha, and leptin receptor mRNA and downregulation of TIMP-1/2 mRNA in the myocardium compared with the sham operation group. Dex treatment significantly ameliorated CHF in association with the reversion of the abnormalities of MMP-2/9, TIMP-1/2, TNF-alpha, and ROS. But Dex had no influence on the hyperleptinemia and the upregulated leptin and its receptor in the myocardium during CHF.. Dex improves CHF by inhibiting TNF-alpha, MMP-2, MMP-9, and ROS. Dex had no effects on upregulated leptin and its receptor expression and hyperleptinemia induced by CHF.

Topics: Animals; Chronic Disease; Dexamethasone; Down-Regulation; Heart Failure; Leptin; Male; Matrix Metalloproteinases; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Leptin; RNA, Messenger; STAT Transcription Factors; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Emerging evidence indicates that leptin may be a potential new target in chronic heart failure (CHF) treatment. We hypothesized that hyperleptinemia may correlate with abnormal expression of SERCA2a, PLB (phospholamban), and the endothelin (ET) pathway in CHF. An activated ET pathway is involved in CHF that is suppressed by CPU86017 (p-chlorobenzyltetrahydroberberine chloride), a complex class III antiarrhythmic agent with an antioxidant effect. Thus, relief of CHF may be mediated by a reversal of abnormalities of the leptin system, the ET-reactive oxygen species (ROS) pathway, SERCA2a, and PLB by CPU86017. CHF was produced by coronary artery ligation for 6 weeks in rats. The rats were divided into 3 groups: sham, CHF untreated, and CHF+CPU86017 (4 mg/kg per day, s.c.). Hemodynamic changes, cardiac morphology, serum biochemistry, messenger ribonucleic acid (mRNA) and protein expression of the leptin pathway, ET pathway, and redox were measured. In CHF rats, hemodynamic abnormalities, cardiac remodeling, and histological changes with features of cardiac failure were associated with hyperlipidemia accompanied by oxidative stress and upregulated OB-Rb, ECE, pp-ET-1, ET(A)R, and ET(B)R mRNA expression in the myocardium. Protein expression of leptin and ET(A)R in the myocardium was markedly increased in CHF rats. An activated leptin pathway was associated with downregulation of SERCA2a and upregulation of PLB in mRNA and protein expression in CHF. CPU86017 downregulated the leptin system and reversed the above changes in the myocardium. An activated leptin pathway correlates with abnormal expression of SERCA2a and PLB and an activated ET-ROS system in the affected myocardium. The multi-ion-channel-blocking and antioxidative effects of CPU86017 downregulate the leptin pathway and ET system, resulting in reversal of the abnormalities of expression of SERCA2a and PLB and cardiac performance in CHF.

Topics: Alkyl and Aryl Transferases; Animals; Anti-Arrhythmia Agents; Antioxidants; Aspartic Acid Endopeptidases; Berberine; Calcium-Binding Proteins; Creatine Kinase; Endothelin-1; Endothelin-Converting Enzymes; Gene Expression; Heart Failure; Heart Rate; L-Lactate Dehydrogenase; Leptin; Male; Metalloendopeptidases; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Transferases (Other Substituted Phosphate Groups); Up-Regulation; Ventricular Function, Left; Ventricular Remodeling

To characterize the immunomodulatory response in a pressure overload model of heart failure, and to further validate this animal model of human heart failure.. Randomized, controlled, animal study.. Large university research facility.. Twenty-seven, male, Sprague-Dawley rats.. The rats underwent either aortic constriction or a sham procedure.. Six months after the surgical procedure, echocardiographic measurements were obtained, the animals were sacrificed, and plasma samples were taken to measure concentrations of biomarkers. As six (40%) of the 15 rats in the aortic-constriction group died before the 6 months, only nine rats from this group underwent immunomodulatory evaluation. Compared with the sham procedure, aortic constriction increased the left ventricle:body weight ratio in the rats (p=0.0016) It also decreased the velocity of circumferential shortening (p=0.08) and increased myocardial expression of atrial natriuretic factor, beta-myosin heavy chain, and fibronectin (p<0.05). Concentrations of the proinflammatory mediator interleukin (IL)-1beta and the counterregulatory mediator IL-10 also significantly increased (p<0.04) in the group that underwent aortic constriction compared with the group that underwent the sham procedure. Nonsignificant increases (mean change approximately 50-180%) were also observed for IL-2, IL-6, and leptin concentrations.. In this classic animal model of heart failure, a systemic immunomodulatory response was evaluated after 6 months of pressure overload resulting in myocardial decompensation and, in some cases, mortality. The findings are similar to the immunomodulatory response that may be observed in human heart failure. These novel results further define this model of heart failure and suggest another aspect of its relevance to human heart failure with regard to pressure overload and the immunomodulatory response.

Topics: Angiogenesis Inducing Agents; Animals; Aortic Coarctation; Atrial Natriuretic Factor; Biomarkers; Blotting, Northern; Disease Models, Animal; Echocardiography; Fibronectins; Gene Expression; Heart Failure; Humans; Inflammation Mediators; Interleukins; Leptin; Male; Myosin Heavy Chains; Pressure; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Time Factors

Adiponectin is a fat-derived hormone involved in the regulation of metabolism. Adiponectin concentration is inversely related to body weight and, in animals, causes weight loss. We, therefore, measured adiponectin concentration in patients with heart failure (HF) and cachexia.. Serum adiponectin concentrations were measured in three groups of patients with coronary artery disease (CAD): (i) HF, reduced left ventricular systolic function, and cachexia (n = 10); (ii) HF, reduced systolic function but no cachexia (n = 20); (iii) HF-controls-patients with CAD, no HF, and preserved systolic function (n = 10); and in a healthy control group (n = 7). Patients with HF and cachexia had higher concentrations of adiponectin [23.8 (10.2-37.2) microg/mL] than all other groups: HF-no cachexia 8.1 (0.5-16.6) microg/mL; CAD-controls 7.1 (0.4-13.5) microg/mL; and healthy controls 8.7 (2.5-16.8) microg/mL) (P < 0.05 for each comparison). Adiponectin correlated negatively with body mass index, percentage of body fat, waist circumference and insulin resistance, and positively with B-type natriuretic peptide (BNP) and tumour necrosis factor-alpha.. Cachexia in HF is associated with an increase in adiponectin concentration. This may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia. The correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.

Topics: Adiponectin; Aged; Body Composition; C-Reactive Protein; Cachexia; Case-Control Studies; Coronary Artery Disease; Female; Glomerular Filtration Rate; Heart Failure; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Stroke Volume

Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG), and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group) consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group) consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group) and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001) in the CHF group (1.4 +/- 0.8 ng/mL) when compared to the IF group (5.3 +/- 5.3 ng/mL), ECG group (9.7 +/- 10.7 ng/mL), and control group (8.1 +/- 7.8 ng/mL). NT-proBNP levels were significantly higher (P < 0.001) in the CHF group (831.8 +/- 800.1 pg/mL) when compared to the IF group (53.2 +/- 33.3 pg/mL), ECG group (83.3 +/- 57.4 pg/mL), and control group (32 +/- 22.7 pg/mL). Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Chagas Cardiomyopathy; Chagas Disease; Echocardiography; Electrocardiography; Female; Fluoroimmunoassay; Heart Failure; Humans; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Data regarding the effectiveness of chronic exercise training in improving survival in patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine the effect of exercise training on survival in a well-defined animal model of heart failure (HF), using the lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present with decompensated, dilated HF between approximately 18 and 23 mo of age. SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of age. Exercise training consisted of 6 mo of low-intensity treadmill running. Exercise training delayed the onset of overt HF and improved survival (P < 0.01), independent of any effects on the hypertensive status of the rats. Training delayed the myosin heavy chain (MyHC) isoform shift from alpha- to beta-MyHC that was seen in sedentary animals that developed HF. Exercise was associated with a concurrent increase in cardiomyocyte length (approximately 6%), width, and area and prevented the increase in the length-to-width ratio seen in sedentary animals in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum leptin levels observed in rats with HF were suppressed by low-intensity exercise training. No significant alterations in sarco(endo)plasmic reticulum Ca2+ ATPase, phospholamban, or Na+/Ca2+ exchanger protein expression were found in response to training. Our results indicate that 6 mo of low-intensity exercise training delays the onset of decompensated HF and improves survival in the male SHHF rat. Similarly, exercise intervention prevented or suppressed alterations in several key variables that normally occur with the development of overt CHF. These data support the idea that exercise may be a useful and inexpensive intervention in the treatment of HF.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Western; Calcium; Cell Separation; Cell Size; Citrate (si)-Synthase; Heart Failure; Isomerism; Leptin; Male; Myocardium; Myocytes, Cardiac; Myosin Heavy Chains; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Survival Analysis

Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25+/-1%, age 56.6+/-1.3 years, Maximal oxygen uptake (VO(2) max) 16.3+/-0.6 ml/min.kg) sub-classified according to peak oxygen consumption of > or 14 ml/min.kg and controls). Elevated levels of leptin correlated with an increased serum concentration of TNFalpha (r=0.749, P<0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

Topics: Aged; Biomarkers; Blood Sedimentation; Body Mass Index; Case-Control Studies; Chronic Disease; Cytokines; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Myocardial Ischemia; Oxygen Consumption; Receptors, Cell Surface; Receptors, Leptin; Severity of Illness Index; Solubility; Statistics as Topic; Stroke Volume; Tumor Necrosis Factor-alpha

The aim of the study was to test the hypothesis that leptin is involved in the regulation of ventilatory responses to exercise in chronic heart failure (CHF).. Exercise-induced hyperventilation is a negative prognostic factor in CHF. Studies in animals suggest that leptin, a hormone secreted by adipocytes, contributes to the regulation of respiration. Plasma leptin levels are elevated in non-cachectic CHF, suggesting the possibility that leptin might be involved in dysregulation of ventilation in CHF.. We studied 50 patients with stable CHF without cachexia. All subjects underwent anthropometric measurements, resting echocardiography, pulmonary function tests, and a cardiopulmonary exercise test. The ventilatory response to exercise was assessed by calculating the VE/VCO(2) and VE/VO(2) slopes (VE = ventilation per unit time, VCO(2) = carbon dioxide production, VO(2) = oxygen consumption).. Using a multiple regression model, leptin was significantly and positively correlated with both VE/VCO(2) slope (regression coefficient = 0.87, F = 39.32, p < 0.001) and VE/VO(2) slope (regression coefficient = 0.84, F = 24.04, p < 0.001). This correlation was independent of age, gender, body mass index, body fat, ejection fraction, New York Heart Association functional class, pulmonary function, plasma norepinephrine, angiotensin II, brain natriuretic peptide levels, and medications. Also, the greatest VE/VCO(2) slope was seen in subjects in the highest tertile of leptin.. Leptin is an independent predictor of VE/VCO(2) slope in heart failure, and may be a link between metabolic, cardiovascular, and respiratory abnormalities in CHF.

Topics: Adult; Exercise; Female; Forced Expiratory Volume; Heart Failure; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Oxygen Consumption; Pulmonary Gas Exchange; Respiration; Vital Capacity

Cachexia is a common problem in chronic heart failure (CHF) that may be partly mediated by activation of the sympathetic nervous system. The effects of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and noncachectic subjects with CHF has not been previously reported.. Body weight and plasma norepinephrine, leptin, and insulin levels were measured in 27 subjects with CHF before and after 6 months of beta-adrenergic receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy, baseline weight, plasma leptin, and plasma insulin levels did not differ between cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were increased in cachectic subjects when compared with noncachectic subjects (930+/-248 pg/mL versus 503+/-109 pg/mL, P=.063). After 6 months of BB therapy, subjects with baseline cachexia demonstrated significantly greater weight gain (+5.2+/-9.6 versus +0.8+/-5.0 kg, P=.027), greater increase in plasma leptin levels (+3.7+/-3.9 versus +1.2+/-4.3 ng/mL, P=.030), and greater decrease in plasma norepinephrine levels (-374+/-261 versus -41+/-122 pg/mL, P=.012) when compared with noncachectic subjects.. Six months of BB therapy with carvedilol or long-acting metoprolol is associated with differential effects on body weight and hormonal levels in cachectic and noncachectic subjects with CHF. Further work is needed to determine the role the sympathetic nervous system in the pathogenesis of cachexia in patients with CHF.

Topics: Adrenergic beta-Antagonists; Biomarkers; Blood Pressure; Body Weight; Cachexia; Carbazoles; Carvedilol; Chronic Disease; Female; Heart Failure; Heart Rate; Humans; Insulin; Leptin; Male; Metoprolol; Middle Aged; Norepinephrine; Propanolamines; Prospective Studies; Severity of Illness Index; Stroke Volume; Treatment Outcome

Chronic heart failure (CHF) has emerged as an insulin-resistant state, independently of ischaemic aetiology. The underlying mechanisms of this finding are not known. Catecholamines, tumor necrosis factor alpha (TNFalpha) and leptin, the adipocyte specific hormone, have all been implicated as mediators of impaired insulin sensitivity. The purpose of this study was to examine in patients with CHF and in comparison to healthy controls subjects whether norepinephrine, TNFalpha or leptin relate to insulin sensitivity.. 41 patients with CHF (age 60+/-2 years, NYHA I/II/III/IV 4/12/22/3, peak oxygen consumption 17.6+/-1.0 ml/kg per min) and 21 healthy controls of similar age and total and regional fat distribution were studied in a cross-sectional study. Insulin sensitivity was assessed by intravenous glucose tolerance testing using the minimal model approach; catecholamines, TNFalpha and soluble TNF receptors 1 and 2 were also measured. Total and regional body fat mass was assessed by dual energy X-ray absorptiometry.. Insulin sensitivity was reduced in CHF patients compared to controls by 31% (P<0.01) and fasting insulin was higher in patients than in controls (79.1+/-9.7 vs. 41.4+/-6.0 pmol/l, P<0.01). Patients had, compared to healthy controls, elevated serum leptin levels (8.28+/-0.84 vs. 4.83+/-0.68 ng/ml), norepinephrine (3.45+/-0.34 vs. 1.87+/-0.16 nmol/l, both P<0.01) and soluble TNF-receptors 1 (1280+/-141 vs. 639+/-52 pg/ml) and 2 (2605+/-184 vs. 1758+/-221 pg/ml, both P<0.01). Leptin levels corrected for total body fat mass were higher in CHF patients than in controls (41.3+/-3 vs. 24.3+/-2 pg/ml per 100 g, P<0.001). TNFalpha was not significantly different between the groups. In both groups there was an inverse correlation between insulin sensitivity and serum leptin (r=-0.65, P<0.0001 for pooled subjects); in contrast, no significant relation was found between insulin sensitivity and norepinephrine or TNFalpha. In multivariate regression analysis, leptin emerged as the only significant predictor of insulin sensitivity (standardised coefficient=-0.59, P<0.001), independent of body fat mass, age and peak VO2.. In moderate CHF, elevated leptin levels directly and independently predict insulin resistance. Elevated serum leptin levels could play a role in the impaired regulation of energy metabolism in CHF. In contrast to observations in other conditions, TNFalpha and norepinephrine are not related to insulin resistance in moderate CHF.

Topics: Adipose Tissue; Blood Glucose; Blood Pressure; Chronic Disease; Creatinine; Cross-Sectional Studies; Heart Failure; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Multivariate Analysis; Norepinephrine; Oxygen Consumption; Predictive Value of Tests; Sensitivity and Specificity; Sodium; Tumor Necrosis Factor-alpha

Advanced chronic heart failure is a hypercatabolic state with an imbalance between anabolic and catabolic metabolism and finally progressive loss of both muscle mass and adipose tissue. Leptin, the product of the obesity gene, is a hormone secreted by adipocytes. Therefore, we tested the hypothesis that plasma leptin concentrations are reduced in advanced chronic heart failure.. In 20 patients with chronic congestive heart failure (LVEF 23 +/- 6%) and 20 healthy controls (LVEF 65 +/- 8%) matched for gender, age, and body mass index, fasting plasma leptin (ELISA) and TNF alpha (ELISA) were measured. Follow-up examination was performed after 1 year.. The fasting plasma leptin concentrations of patients with NYHA grade III (8.4 +/- 3.8 ng/ml*) and NYHA grade IV (4.6 +/- 2.4 ng/ml dagger) were significantly lower as compared with the controls (11.2 +/- 3.1 ng/ml; *p < 0.05, dagger p < 0.01). In patients with NYHA grade II plasma leptin levels were significantly elevated as compared with the healthy controls (14.9 +/- 4.2 ng/ml). TNF alpha was higher in heart failure patients than in healthy controls (8.6 +/- 3.6 pg/ml; 5.9 +/- 2.1 pg/ml; respectively; p < 0.05), but did not correlate with the NYHA functional class. Mortality of the controls was 0%, whereas 15% (n = 3) in the congestive heart failure group; one patient (5%) needs an urgent heart transplantation. All of those patients had leptin concentrations below 5 ng/ml.. Plasma leptin concentrations correlate with the NYHA functional class suggesting anabolic metabolism in NYHA class II and catabolic metabolism in advanced heart failure which might be of prognostic relevance.

Topics: Adult; Body Mass Index; Chronic Disease; Energy Metabolism; Female; Heart Failure; Humans; Leptin; Male; Matched-Pair Analysis; Middle Aged; Prognosis; Reference Values; Tumor Necrosis Factor-alpha

Topics: Body Mass Index; Cachexia; Heart Failure; Humans; Leptin; Sympathetic Nervous System

Topics: Adipose Tissue; Catecholamines; Chronic Disease; Heart Failure; Humans; Insulin; Leptin; Obesity; Proteins; Sympathetic Nervous System

Cardiac cachexia is a syndrome of generalised wasting which caries a poor prognosis and is associated with raised plasma concentrations of tumour necrosis factor alpha (TNFalpha). TNFalpha increases secretion of leptin, a hormone which decreases food intake and increases energy expenditure.. To determine whether an inappropriate increase in plasma leptin concentration contributes to the cachexia of chronic heart failure.. Retrospective case-control study.. Tertiary referral cardiology unit.. 110 human subjects comprising 29 cachectic chronic heart failure patients, 22 non-cachectic chronic heart failure patients, 33 patients with ischaemic heart disease but normal ventricular function, and 26 healthy controls.. Measurement of: body fat content by skinfold thickness (cachectic males < 27%, females < 29%); plasma leptin, TNFalpha, and noradrenaline (norepinephrine); central haemodynamics in chronic heart failure patients at right heart catheterisation.. Plasma leptin concentration corrected for body fat content, plasma TNFalpha and noradrenaline concentration, and central haemodynamics.. Mean (SEM) plasma leptin concentrations were: 6.2 (0.6) ng/ml (cachectic heart failure), 16.9 (3.6) ng/ml (non-cachectic heart failure), 16.8 (3.0) ng/ml (ischaemic heart disease), and 18.3 (3.5) ng/ml (control) (p < 0.001 for cachectic heart failure v all other groups). Plasma leptin concentration remained significantly lower in the cachectic heart failure group even after correcting for body fat content and in spite of significantly increased TNFalpha concentrations. Thus plasma leptin was inappropriately low in cachectic chronic heart failure in the face of a recognised stimulus to its secretion. There was no significant correlation between plasma leptin, New York Heart Association class, ejection fraction, or any haemodynamic indices.. Leptin does not contribute to the cachexia of chronic heart failure. One or more leptin suppressing mechanisms may operate in this syndrome-for example, the sympathetic nervous system.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cachexia; Case-Control Studies; Chronic Disease; Female; Heart Failure; Hemodynamics; Humans; Leptin; Male; Middle Aged; Norepinephrine; Proteins; Retrospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels.. Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels.. Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001).. Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.

Topics: Adipose Tissue; Biomarkers; Body Mass Index; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Heart Failure; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay

Leptin, the protein encoded by the obese gene, is a newly described hormone implicated in the regulation of energy balance. To examine the possible role of leptin in the energy dysregulation that frequently accompanies chronic heart failure, we examined plasma leptin concentrations and energy expenditure in 18 heart failure patients (aged 71 +/- 6 years) and 46 healthy elderly controls (66 +/- 6 years). Plasma leptin concentrations were measured by radioimmunoassay, daily energy expenditure by doubly labeled water, and body composition by dual-energy x-ray absorptiometry. Fat mass was lower (P < .01) in heart failure patients compared with healthy controls, whereas fat-free mass did not differ between groups. Plasma leptin concentrations were not different between heart failure patients and healthy controls (5.1 +/- 4.2 v 6.8 +/- 4.4 pg/mL) and remained similar after statistical control for fat mass (6.0 +/- 3.1 v 7.1 +/- 3.2 pg/mL). Plasma leptin was related to fat mass in heart failure patients (r = .92, P < .01) and healthy controls (r = .69, P < .01). Free-living daily and physical-activity energy expenditures were lower (P < .01) in heart failure patients compared with healthy controls. Plasma leptin concentrations were related to both daily (r = .67, P < .01) and resting (r = .67, P < .01) energy expenditure in heart failure patients, but not in healthy controls (r = .09 and r = .33, respectively). In conclusion, we found an association between plasma leptin concentrations and energy expenditure in heart failure patients, but not in healthy controls. Thus, leptin may participate in the regulation of energy expenditure and body energy stores in heart failure patients.

Topics: Aged; Energy Metabolism; Female; Heart Failure; Humans; Leptin; Male; Proteins