leptin and Coronary-Artery-Disease

Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions.. Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups.. Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them.. Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Coronary Artery Disease; Humans; Leptin; Obesity; Polymorphism, Genetic; Receptors, Leptin

Topics: Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Leptin; Polymorphism, Genetic; Receptors, Leptin

This meta-analysis aimed to investigate the association of leptin levels with pathogenetic risk of CHD and stroke.. Studies were identified in the PubMed, Embase, and Springer link database without language restriction. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used as effect indexes. The association of leptin levels with pathogenetic risk of CHD and stroke, as well as the risk variation of CHD with each additional one unit of leptin level were examined via meta-analysis. The publication bias was assessed via Egger's linear regression test.. Eight nested case-control studies consisting of 1,980 patients and 11,567 controls were included for current meta-analysis. ORs (95% CIs) of association of leptin levels with CHD and stroke was 1.90 (1.06, 3.43), and 2.14 (1.48, 3.08), respectively. In addition, significant result was obtained regarding the risk variation of CHD with each additional one unit of leptin level (OR =1.04, 95% CI =1.00-1.08, P=0.044). There was no significant publication bias as suggested by Egger test outcomes.. There was a significant association of leptin with pathogenetic risk of CHD and stroke, and raised leptin levels could significantly increase the pathogenetic risk of CHD.

Topics: Biomarkers; Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Leptin; Odds Ratio; Risk; Stroke

Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and involved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue. These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

Topics: Adipose Tissue; Cardiovascular Diseases; Coronary Artery Disease; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Myocardium; Myocytes, Cardiac; Obesity; Ventricular Remodeling; Weight Loss

Obesity is becoming a global epidemic. Around 1.1 billion adults and 10% of the world's children are currently overweight or considered obese. Generally associated with risk factors for cardiovascular disease, such as Diabetes Mellitus and systemic arterial high blood pressure, the obesity has been more and more seen as an independent risk factor for Coronary Artery Disease (CAD). Coronary arteriosclerosis comprises a series of inflammatory responses at cellular and molecular level, whose reactions are stronger in obese patients. In the past, the adipose tissue was regarded as a mere fat deposition. Now it is seen from a totally different standpoint, as an active endocrine and paracrine organ that produces several inflammatory cytokines, such as the adipokines. This article aims to raise awareness about obesity as an increasingly significant public health issue over the past decades, as well as to relate the intense inflammatory process in obese individuals with an increased tendency for this group of individuals to develop CAD.

Topics: Adiponectin; C-Reactive Protein; Coronary Artery Disease; Endothelium, Vascular; Humans; Inflammation Mediators; Leptin; Obesity; Risk Factors; Vasculitis

Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease.

Topics: Calcinosis; Coronary Artery Disease; Humans; Leptin; Proteins; Vitamin K

Atherosclerosis is a chronic inflammatory disease characterized by infiltration of blood vessels by lipids and leukocytes. There is a growing body of evidence that among risk factors that promote atherosclerosis, the metabolic syndrome is a powerful and prevalent predictor of cardiovascular events. The systemic inflammatory process associated with the metabolic syndrome has numerous deleterious effects that promote plaque activation, which is responsible for clinical events. Interactions between the innate immune system with lipid-derived products seem to play a major role in the pathophysiology of atherosclerosis in relation with the metabolic syndrome. The multiple links among adipose tissue, the vascular wall, and the immune system are the topics of this review, which examines the roles of oxidized low-density lipoprotein, inflammatory cytokines, and adipokines in triggering and perpetuating a danger signal response that promotes the development of atherosclerosis. Furthermore, therapeutic options that specifically target the metabolic syndrome components are reviewed in light of recent developments.

Topics: Adipose Tissue; C-Reactive Protein; Cholesterol, LDL; Coronary Artery Disease; Coronary Disease; Endothelium, Vascular; Genetic Predisposition to Disease; Humans; Immunity; Leptin; Metabolic Syndrome; Peroxisome Proliferator-Activated Receptors; PPAR alpha; PPAR delta; Receptors, Scavenger; Resistin; Risk Factors; Toll-Like Receptors

The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as NGF, BDNF, leptin and MC may be involved in the development of cardiovascular disease and related disorders.

Topics: Animals; Brain-Derived Neurotrophic Factor; Coronary Artery Disease; Coronary Vessels; Humans; Leptin; Mast Cells; Metabolic Syndrome; Nerve Growth Factor; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor; Serine Endopeptidases

Increased leptin and decreased adiponectin levels are reported in coronary artery disease (CAD) as well as in obstructive sleep apnoea (OSA). Less is known regarding the impact of continuous positive airway pressure (CPAP) on these biomarkers. We aimed to determine variables associated with leptin and adiponectin in adults with CAD and nonsleepy OSA, and evaluate the effect of CPAP adjusted for confounding factors.. This was one of the secondary outcomes of the RICCADSA trial, conducted in Sweden between 2005 and 2013. From 244 revascularized CAD and OSA patients (apnoea-hypopnoea index >15/h) without excessive daytime sleepiness (Epworth Sleepiness Scale score <10), 196 with blood samples at baseline, after 3, and 12 months were included in the randomized controlled trial arm; of those, 98 were allocated to auto-titrating CPAP, and 98 to no-CPAP.. No significant changes in leptin and adiponectin levels were observed during follow-up, whereas Body-Mass-Index and waist circumference increased in both CPAP and no-CPAP groups with no significant between-group differences. Alterations in plasma leptin were determined by changes in waist circumference (beta coefficient 2.47; 95% confidence interval 0.77-4.40), whereas none of the analyzed parameters was predictive for changes in adiponectin levels. No association was found with CPAP adherence.. CPAP had no significant effect on leptin and adiponectin in this cohort of nonsleepy OSA patients. An increase in waist circumference predicted an increase in plasma levels of leptin after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA regardless of CPAP treatment.

Topics: Adiponectin; Aged; Biomarkers; Cohort Studies; Continuous Positive Airway Pressure; Coronary Artery Disease; Female; Humans; Leptin; Male; Sleep Apnea, Obstructive; Sweden

The aim of this research was to assess the relationship between plasma adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-α) levels and echocardiographic parameters of ventricular remodeling in patients with coronary artery disease, without acute myocardial infarction. The study population consisted of 49 patients with echocardiographic measurements performed. After adjustment for age, gender, body mass index, systolic and diastolic blood pressure, and glycaemia, adiponectin was statistically significant associated with interventricular septum thickness (β = -0.304), left ventricular posterior wall thickness (β = -0.402), left ventricular end diastolic diameter (LVEDD; β = 0.385) and left ventricular relative wall thickness (β = -0.448, p < .05 for all). The associations were no longer significant when only patients without diabetes were included in the analysis. Leptin was associated with LVEDD (β = -0.354) and left ventricular relative wall thickness (β = 0.385, p < .05 for all). No associations between resistin, TNF-α and echocardiographic left ventricular parameters assessed were found in these patients. In conclusion, in patients with coronary artery disease and without acute myocardial infarction leptin may represent a potential mechanism of adverse cardiac remodeling. Resistin and TNF-α might not be involved in ventricular remodeling in these patients.

Topics: Adiponectin; Aged; Coronary Artery Disease; Echocardiography; Humans; Leptin; Middle Aged; Prospective Studies; Resistin; Tumor Necrosis Factor-alpha; Ventricular Remodeling

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

The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance.. Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics.. A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.

Topics: Analysis of Variance; Blood Glucose; Body Mass Index; Cholesterol, HDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Exercise Tolerance; Glycated Hemoglobin; Heart Septum; Humans; Hypertrophy; Insulin; Leptin; Male; Prediabetic State; Testosterone; Triglycerides; Waist Circumference

Growing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.. We sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).. We conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3-5 days and 30 days during administration of omega-3 PUFA 1 g/day (n=20) or placebo (n=28).. As compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4% (P<0.0001), reduction of leptin by 22% (P<0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5% (P<0.0001) at 30 days, but not at 3-5 days. Compared with placebo adiponectin was 12.7% higher (P=0.0042), leptin was 16.7% lower (P<0.0001) and A/L ratio was 33.3% higher (P<0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P=0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P<0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P<0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P<0.0001) were: assigned treatment, current smoking and hyperlipidemia.. In high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.

Topics: Adiponectin; Aged; Cardiotonic Agents; Coronary Artery Disease; Double-Blind Method; Fatty Acids, Omega-3; Female; Humans; Leptin; Male; Middle Aged; Percutaneous Coronary Intervention; Resistin

Leptin has been reported to exert an atherosclerotic effect by regulating expression of angiogenic factors that have been implicated in the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate whether lipid-lowering therapy (LLT) with statins could affect leptin levels and angiogenic factors in patients with CAD. This study included 76 patients with CAD and 15 subjects without CAD (non-CAD). CAD patients were randomized to 6 months of intensive LLT with atorvastatin or moderate LLT with pravastatin. Plasma leptin, angiopoetin-2 (Ang-2), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels were measured prior to statin therapy (baseline) and after 6 months. Baseline levels of leptin, Ang-2, HGF and VEGF were higher in the CAD group than in the non-CAD group (all P < 0.05). Treatment with intensive LLT decreased leptin, Ang-2, HGF and VEGF levels, whereas moderate LLT did not change these levels. This study suggests that LLT with atorvastatin decreases leptin levels and angiogenic factors in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in CAD.

Topics: Aged; Analysis of Variance; Angiogenic Proteins; Angiopoietin-2; Atorvastatin; Biomarkers; Coronary Artery Disease; Down-Regulation; Female; Hepatocyte Growth Factor; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Leptin; Lipids; Male; Middle Aged; Pravastatin; Prospective Studies; Pyrroles; Single-Blind Method; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A

This study was designed to examine the influence of exercise training on leptin levels in patients with stable coronary artery disease (CAD).. Sixty-four male patients, mean age 55.6 ± 6.0 years, were randomized either to six weeks of aerobic training, three times a week, at 60-80% of maximal heart rate (training group, Ex, n = 32) or to a control group (n = 32). Exercise stress test was performed and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference and plasma leptin levels were measured at the beginning and end of the study.. Physical capacity increased significantly only in Ex patients (max workload in METs from 7.7 ± 1.4 to 8.2 ± 1.4, p < 0.05). There were no significant differences between initial and final results in either group in terms of BMI, WHR or waist circumference. Although, at the end of the study, leptin levels did not change in Ex patients (6.7 ± 3.2 vs 6.9 ± 3.6 ng/mL, NS), they did increase significantly in the control group (8.0 ± 4.0 vs 9.3 ± 5.2 ng/mL, p < 0.02).. A short period of exercise training in CAD patients improved their physical capacity, but did not influence BMI, WHR and waist circumference. Exercise training prevented an increase in leptin levels during the study period.

Topics: Adipose Tissue; Body Mass Index; Coronary Artery Disease; Exercise; Exercise Test; Exercise Therapy; Humans; Leptin; Male; Middle Aged; Pilot Projects; Waist-Hip Ratio

Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood.. For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation.. The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 +/- 1.57 microg/mL vs CABG: 9.11 +/- 15.7 microg/mL; p < 0.001) and resistin (control: 10.53 +/- 0.81 ng/mL vs CABG: 16.8 +/- 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 +/- 14.8 microg/mL vs CABG: 11.9 +/- 6.0 microg/mL; p < 0.05) when compared to BMI matched controls.. Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease.

Topics: Adiponectin; Adipose Tissue; C-Reactive Protein; Coronary Artery Bypass; Coronary Artery Disease; Cytokines; Gene Expression Profiling; Gene Expression Regulation; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Interleukin-6; Intra-Abdominal Fat; Leptin; Leukocyte Common Antigens; Macrophages; Middle Aged; Pericardium; Polymerase Chain Reaction; Potassium; Resistin; RNA, Messenger

In the present study, the relationship between plasma leptin and other cardiovascular risk factors in high-risk postmenopausal women was assessed, as well as the effect of transdermal 17beta-estradiol unopposed or in combination with intermittent medroxyprogesterone acetate (MPA) on plasma leptin.. Postmenopausal women (n = 118) with coronary artery disease (CAD) were consecutively recruited from women admitted to hospital for coronary angiography. They were randomized to estradiol plus intermittent MPA or to a control group, and investigated at study inclusion, and after 3 and 12 months.. A strong relationship was found between leptin and body mass index (r = 0.69, p < 0.001). Leptin was related to lipid fractions (high-density lipoprotein cholesterol: r = -0.33, p < 0.001; apolipoprotein A: r = -0.28, p = 0.004; and triglycerides: r = 0.27, p = 0.003) and indices of glucose metabolism (C-peptide: r = 0.47, p < 0.001; fasting insulin: r = 0.42, p < 0.001; glucose: r = 0.25, p = 0.008; insulin resistance: r = 0.45, p < 0.001; and insulin secretion: r = 0.36, p < 0.001). In a multiple regression model, only body mass index (p < 0.001) and C-peptide (p = 0.002) remained as independent factors for leptin levels. Despite the association with sex hormone-binding globulin (r = 0.30, p = 0.001), no effect on leptin levels was observed with either unopposed transdermal estradiol or estradiol combined with MPA.. Plasma leptin is related to other cardiovascular risk factors in postmenopausal women with CAD, but seems to be unaffected by transdermal 17beta-estradiol administration.

Topics: Administration, Cutaneous; Aged; Blood Glucose; Body Mass Index; C-Peptide; Climacteric; Coronary Angiography; Coronary Artery Disease; Diabetes Complications; Estradiol; Female; Humans; Insulin; Leptin; Lipids; Medroxyprogesterone Acetate; Middle Aged; Postmenopause; Risk Factors; Treatment Outcome

To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA).. Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted.. Among 2,598 participants, 639 (25%) had at least 1 CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (hazard ratio [HR] 1.39 [95% confidence interval (95% CI) 1.07-1.79], P = 0.01) and CVD-related death (HR 1.49 [95% CI 1.16-1.92], P = 0.002) but not with other CVD events. High leptin was independently associated with CVD-related death (HR 1.44 [95% CI 1.05-1.97], P = 0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR 0.75 [95% CI 0.58-0.97], P = 0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in nonobese patients.. Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in nonobese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.

Topics: Adipokines; Adiponectin; Arthritis, Rheumatoid; Cardiovascular Diseases; Coronary Artery Disease; Humans; Leptin; Risk Factors

Topics: Adiponectin; Biomarkers; Coronary Angiography; Coronary Artery Disease; Humans; Interleukin-6; Leptin; Risk Factors

Adipokines have been associated with increased risk of cardiovascular disease. Our aim was to determine if adipokine levels are associated with coronary artery calcification (CAC) as well as all-cause mortality in incident dialysis patients.. In patients new to dialysis, we prospectively investigated the association of adiponectin, leptin and resistin with coronary artery calcification measured by ECG-gated computer tomography. Participants were recruited a median of two months after starting dialysis.. The mean age was 50.0 (12.6) years and 31.1% were women. About 42% percent had BMI > 30. Higher adiponectin levels were inversely associated with CAC progression as change in Agatston score [-155.1 (-267.9, -42.2), p = 0.008] or change in CAC volumes between scans [-2.8 (-4.9, -0.6), p = 0.01]. Higher leptin levels were associated with CAC progression [110.4 (34.3-186.6), p = 0.005]. Decreased leptin [HR 0.5 (0.3-0.9), p = 0.05] was associated with all-cause mortality in adjusted models. There was no significant association between all-cause mortality and adiponectin [1.4 (0.6-3.4), p = 0.4] or resistin [HR 1.7 (0.5-5.0), p = 0.4].. High adiponectin protects against CAC progression, but is not associated with increased all-cause mortality. Higher leptin, as well as higher leptin to adiponectin ratio, is associated with CAC progression. Lower leptin levels were associated with all-cause mortality. The association of adipokines and cardiovascular disease in individuals on dialysis is complex and requires further study.

Topics: Adipokines; Adiponectin; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Leptin; Male; Middle Aged; Renal Dialysis; Resistin; Risk Factors; Vascular Calcification

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

Epicardial adipose tissue (EAT) dysfunction mediates chronic inflammation by regulating inflammation-related adipokines and cytokines, and it further promotes coronary artery disease (CAD) development. CD40L/CD40 is involved in multiple inflammatory pathways that contribute to various pathophysiological processes. However, the function of CD40L/CD40 in the expression and production of adipokines and cytokines in epicardial adipocytes remains unclear. The purpose of the present study was to explore the role and underlying mechanisms of CD40L/CD40 in adipokine and cytokine expression and production. We isolated adipocytes from EAT tissues of CAD and non-CAD patients. We noticed that CD40 was dramatically increased in EAT tissues of CAD patients. Loss-of-function and gain-of-function studies were performed. The results showed that CD40 silencing reduced recombinant CD40 ligand (rCD40L)-induced upregulation of plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 messenger RNA levels and secretion. Overexpression of CD40 displayed the opposite results. In addition, rCD40L triggered mixed lineage leukemia protein-1 (MLL1) expression both in messenger RNA and protein levels. CD40 depletion apparently blocked MLL1 expression, whereas gain of function of CD40 resulted in augmentation of MLL1 levels. Interestingly, chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis revealed that CD40 elimination dampened histone H3 lysine 4 trimethylation enrichment at plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 promoter regions in the presence of rCD40L. The reverse pattern was observed upon ectopic expression of CD40. Most important, MLL1 silencing effectively reversed the promotive effects of CD40 on adipokine and cytokine secretion. Taken together, our findings suggest that CD40L/CD40 regulates adipokine and cytokine expression by H3 lysine 4 trimethylation modification in adipocytes.

Topics: Adipocytes; Adipokines; Aged; Case-Control Studies; CD40 Antigens; CD40 Ligand; Cells, Cultured; Chemokine CCL2; Coronary Artery Disease; Cytokines; Female; Histone-Lysine N-Methyltransferase; Histones; Humans; Interleukin-6; Leptin; Male; Methylation; Middle Aged; Myeloid-Lymphoid Leukemia Protein; Pericardium; Plasminogen Activator Inhibitor 1; Promoter Regions, Genetic; Protein Processing, Post-Translational

Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD.. We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system.. The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males.. The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

Topics: Aged; Body Mass Index; Case-Control Studies; China; Coronary Artery Disease; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Leptin; Risk Factors

Obesity is related to coronary artery disease (CAD) and worse outcomes in coronary artery bypass graft (CABG) patients. Adipose tissue itself is an endocrine organ that secretes many humoral mediators, such as adipokines, which can induce or reduce inflammation and oxidative stress.. We investigate the relationship between the body mass index (BMI), inflammation, and oxidative stress by measuring serum levels of leptin, interleukin-6, and 3-nitrotyrosine in CABG patients and correlate their levels to the cardiovascular and operative risk profiles.. 45 men (<75 years) with a median BMI of 29 (21-51) kg/m. There seems to be a correlation between inflammatory processes and cardiovascular morbidity in our cohort. Further, the incidence of deep sternal wound infections is related to a higher BMI and leptin serum level.

Topics: Aged; Body Mass Index; Coronary Artery Bypass; Coronary Artery Disease; Humans; Inflammation; Leptin; Male; Middle Aged

Chronic inflammation plays a role in all stages of atherosclerosis leading to coronary artery disease (CAD), with elevated inflammatory markers being associated with the worse clinical outcome. The goal of the current study was to examine possible association between pro-inflammatory/pro-coagulant factors; anticardiolipin (aCL) autoantibodies, complement C3, C4 and leptin, and the severity of CAD expressed as SYNTAX score. Patients with symptoms of cardiac ischemia undergoing coronary angiography were recruited, and their blood levels of aCL-IgG, aCL-IgM, complement C3, C4 and leptin were assessed. Their association with the SYNTAX score, calculated based on coronary angiography findings, was analyzed. All patients had aCL antibody titer within the normal range. A significant positive association was found for aCL-IgG and SYNTAX score. Male patients had higher average aCL-IgG concentration and SYNTAX score than female patients. No association was found between SYNTAX score and C3 and C4. On the other hand, leptin was negatively associated with SYNTAX score. Our study demonstrates an association between the extent of CAD and aCL-IgG even in the absence of systemic autoimmune disease and at the aCL-IgG levels that are within the normal range. Also, association of lower leptin levels with more severe CAD suggests that its pro-inflammatory effects might not contribute to the pathogenesis of CAD, and that leptin might even exert protective effects on coronary vasculature.

Topics: Aged; Antibodies, Anticardiolipin; Biomarkers; Case-Control Studies; Complement C3; Complement C4; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index

Leptin can have a direct effect on endothelial and vascular smooth muscle cells and high level of leptin is involved in the pathogenesis of atherosclerosis. This study aimed to determine the relationship between leptin/adiponectin (L/A) ratio and the extent and severity of coronary artery disease (CAD).. This case-control study was conducted in an educational hospital in Ilam, Iran from June 2014 to September 2015. Totally 300 participants including 150 patients with CAD (case group) and 150 healthy individuals (control group) were selected and their plasma leptin, adiponectin and leptin/adiponectin ratio was measured. The extent and severity of coronary artery disease were assayed based on the number of involved vessels and Gensini score (GS) and the relation between scores and L/A findings were compared between cases and controls.. Totally, 300 participants including 150 (42.7% male), mean age 59.5 ± 11.4 years as cases and 150 (50.7% male), mean age 59.8 ± 10.7 as controls were analyzed. Plasma level of leptin and L/A ratio were higher in cases compared to controls, but level of adiponectin was significantly lower in CAD patients than the control group. More number of involved coronary vessels was significantly correlated to higher level of plasma leptin, L/A ratio and lower level of adiponectin among case group. Moreover, adiponectin was negatively and leptin or L/A ratio were positively correlated with number of involved vessels. 7.3% of cases had only one involved vessel, 42.7% had two involved vessels, and 50% of total patients had involved vessels and the mean ± SD of GS in the case group was 23.6 ± 6.9.. Plasma levels of leptin, and adiponectin can indicate the extent of coronary artery diseases but leptin may be a better marker of extent of CAD than either L/A ratio or adiponectin separately.

Topics: Adiponectin; Aged; Biomarkers; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Female; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index

Mediastinal fat has been suggested to be associated with cardiovascular diseases such as carotid stiffness, atherosclerosis and coronary artery calcification. We investigated the possible role of Ad-36-induced obesity in the pathogenesis of the coronary artery disease (CAD). Ad-36 DNA was investigated in the anterior mediastinal fat tissue samples of obese adults with CAD. Seventy-five obese adults with left main coronary artery (LMCA) disease, 28 non-obese adults with valvular heart diseases, and 48 healthy individuals without cardiovascular problems were included as the obese patient group (OPG), non-obese patient group (NOG) and healthy control group (HCG), respectively. We also simultaneously investigated Ad-36 antibodies by serum neutralization test (SNA), and measured leptin and adinopectin levels. Ad-36 antibodies were detected only in 10 patients (13.3%) within the 75 OPG. A statistically significant difference was detected between OPG, NOG and HCG in terms of Ad-36 antibody positivity (p>0.05). Ad-36 DNA was not detected in mediastinal tissue samples of OPG and NOP without PCR inhibitors. We suggest that Ad-36 may not have an affinity for mediastinal adipose tissue in obese patients with left main CAD and valvular heart diseases. Ad-36 antibody positivity results are not sufficient to reach a causal relationship.

Topics: Adenoviruses, Human; Adipogenesis; Adiponectin; Adipose Tissue; Adult; Antibodies, Viral; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; DNA, Viral; Female; Heart Valve Diseases; Humans; Leptin; Male; Mediastinum; Middle Aged; Obesity; Vascular Calcification; Waist-Hip Ratio

BACKGROUND Leptin is an adipokine related to overweight and cardiovascular diseases. However, the leptin expression level in epicardial adipose tissue (EAT) of humans and its association with coronary atherosclerosis has never been investigated. MATERIAL AND METHODS Patients receiving cardiac surgery were divided into a coronary artery disease group (CAD group) and a non-CAD group (NCAD group). Blood samples from coronary vein, biopsies of subcutaneous adipose tissue (SAT), and EAT were acquired during the surgery. Serum leptin level and leptin level in EAT and SAT were tested with ELISA, quantitative PCR, and immunohistochemistry and were compared between the CAD group and NCAD group, as well as between stenosis and non-stenosis subgroups. Logistic regression analysis was performed to explore the risk factors for coronary artery stenosis. RESULTS No statistically significant differences were found in demographic and clinical data between groups (all P>0.05). Serum leptin concentration and leptin expression in EAT and SAT of the CAD group were much higher in than in the NCAD group (all P<0.05). In subgroup analysis, there was no difference in serum leptin and expression in SAT of stenosis and non-stenosis patients (All P>0.05). The leptin expression level in EAT of stenosis patients was significantly higher than in non-stenosis patients (P=0.0431). By multivariate logistic regression analysis, we demonstrated that leptin expression level in EAT was an independent risk factor for coronary artery stenosis [OR=1.09, 95%CI (1.01±1.18), P=0.031]. CONCLUSIONS Leptin expression in EAT and SAT were both increased for CAD patients. Leptin expression in EAT was an independent risk factor for coronary atherosclerosis in the adjacent artery, while leptin in SAT was not associated.

Topics: Adipokines; Adipose Tissue; Aged; Coronary Artery Disease; Coronary Stenosis; Female; Gene Expression; Humans; Leptin; Male; Middle Aged; Pericardium; Real-Time Polymerase Chain Reaction; Risk Factors; Subcutaneous Fat

The role of the adipokines in the pathogenesis of aortic stenosis (AS) is not well established. The aim was to evaluate the relationship between adipokines and clinical characteristics as well as echocardiographic indices and noninvasive markers of vascular remodeling in patients with severe AS with preserved ejection fraction (EF).. Sixty-five patients (F/M: 38/27; age: 68.3 ± 9.0 years; body mass index [BMI]: 29.6 ± 4.3 kg/m2) with severe AS with preserved EF: 33 patients with paradoxical low-flow low-gradient AS (PLFLG AS) and 32 patients with normal flow high-gradient AS (NFHG AS) were prospectively enrolled into the study. Twenty-four subjects (F/M: 14/10; age: 65.4 ± 8.7 years; BMI: 29.6 ± 4.3 kg/m2) who matched as to age, sex, BMI and coronary artery disease (CAD) constituted the control group (CG). Clinical data and markers of vascular remodeling were related to the serum adipokines.. There were no differences in the adipokines concentrations in the AS/CG. Patients with AS and coexisting CAD were characterized by decreased serum adiponectin (9.9 ± 5.5 vs. 12.7 ± 5.8 μg/mL, p = 0.040) and leptin (8.3 ± 7.8 vs. 21.6 ± 17.1 ng/mL, p < 0.001) levels compared to subjects without CAD. There were no differences in the serum adipokines concentrations between patients with PLFLG AS and NFHG AS. Systemic hypertension, diabetes, hyperlipidemia or markers of vascular remodeling did not discriminate adipokines concentrations. Multivariate regression analysis indicated that age (F = 3.02; p = 0.015) and E/E' index (F = 0.87, p = 0.032) were independent predictors of the adiponectin level in the AS group.. The presence of AS with preserved EF did not change the adipokine serum profile. Adipokines levels were modified by coexisting atherosclerosis but not the typical cardiovascular risk factors or the hemodynamic type of AS.

Topics: Adipokines; Adiponectin; Aged; Aortic Valve Stenosis; Biomarkers; Case-Control Studies; Coronary Artery Disease; Cytokines; Female; Humans; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Prospective Studies; Resistin; Severity of Illness Index; Stroke Volume; Vascular Remodeling; Ventricular Function, Left

Vitamin D is a fat soluble vitamin involved in calcium and bone metabolism; recently its deficiency has been related to cardiovascular disease. In cardiac tissue, vitamin D suppresses metalloproteinases (MMPs) expression, enzymes directly associated with vulnerable plaque.. To investigate whether the association between vitamin D and leptin is related to markers of vulnerable plaque, such as MMPs in patients with acute myocardial infarction.. We studied 66 male patients with acute myocardial infarction, undergoing primary angioplasty. Blood samples were obtained at admission and 24hs after the surgery. Leptin and vitamin D concentrations in serum and MMP-2 and -9 activities in plasma were determined.. MMP-2 activity was increased in Vitamin D deficient/insufficient patients at admission (p=0.04) and 24 hs later (p=0.05). In a linear regression model, vitamin D explained 24% of the variance of MMP-2 activity (F=2.839 p=0.04). At admission, vitamin D correlated with serum leptin (r=-0.302 p=0.033), and explained 39.5% of its variation (F=4.432 p=0.003).. In the studied population, vitamin D was inversely related to MMP-2 and leptin which are involved in coronary artery disease and acute myocardial infarction. The decrease in this hormone levels would be associated with a worse metabolic profile in acute coronary syndrome patients.

Topics: Adult; Aged; Biomarkers; Coronary Artery Disease; Humans; Leptin; Male; Matrix Metalloproteinase 2; Middle Aged; Plaque, Atherosclerotic; Rupture, Spontaneous; ST Elevation Myocardial Infarction; Time Factors; Vitamin D; Vitamin D Deficiency

Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD).. In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA.. The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; r = 0.28, p = 0.016), WBCC (r = 0.261, p = 0.02), neutrophil, r = 0.268, p = 0.018, and monocyte, r = 0.228, p = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (β = 0.317, p = 0.004), WBCC (β = 0.278, p = 0.020), neutrophil (β = 0.262, p = 0.032), and monocyte (β = 0.245, p = 0.032).. The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients.

Topics: Adult; Aged; Asian People; Biomarkers; C-Reactive Protein; Case-Control Studies; China; Coronary Angiography; Coronary Artery Disease; Female; Humans; Inflammation; Leptin; Leukocyte Count; Male; Middle Aged

Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA.. We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC.. Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men (p < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE.. IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Asian People; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Tumor Necrosis Factor-alpha; United States; Vascular Calcification

Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%-85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11-12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.

Topics: Animals; Arterioles; Biomarkers; Blood Glucose; Coronary Artery Disease; Coronary Vessels; Disease Models, Animal; Female; Glucose Tolerance Test; Gonadal Steroid Hormones; Hyperandrogenism; Insulin; Insulin Resistance; Leptin; Polycystic Ovary Syndrome; Rats, Wistar; Time Factors; Vascular Resistance; Vasodilation; Vitamin D; Vitamin D Deficiency

Apelin and leptin are factors which have a potential physiological and pathological role in cardiovascular homoeostasis. Apelin receptor (APLNR), leptin receptor (LEPR) and leptin variants may affect the vascular tone in heart or peripheral circulation, thereby predisposing patients to hypertension and coronary artery disease (CAD). The aim of the present study was to evaluate four single nucleotide polymorphisms (SNPs) of APLNR genes (rs11544374 and rs948847), LEPR (rs1137101) and leptin (rs7799039) gene in patients with CAD and hypertension.. This case-control study was carried out on 286 CAD-suspected patients. The participants were divided into four subgroups including: CAD patients with no hypertension (H. A significant difference was found in the genotype frequency of APLNR rs11544374 gene in H. The findings of present study revealed that the APLNR rs11544374 gene polymorphism might serve as predisposing factor in CAD.

Topics: Adult; Aged; Alleles; Apelin Receptors; Body Mass Index; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Iran; Leptin; Lipid Metabolism; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Receptors, Leptin

Adipokines are known to predict cardiovascular events, yet their association with coronary artery calcium (CAC), a surrogate marker of coronary atherosclerosis and risk factor for cardiovascular disease (CVD), is unclear. We aimed at assessing the association between adipokines and the severity and progression of CAC in healthy older adults, and at exploring potential modification by gender.. 409 men and women from the Rancho Bernardo Study with no known CVD underwent a chest computed tomography scan to determine baseline CAC severity; 329 returned 4.5 years later for a repeat scan to evaluate CAC progression. Adipokines (IL-6, adiponectin, leptin, and TNF-α) were measured from baseline blood samples. Ordinal linear and logistic regression models were used to determine the association of each adipokine with baseline severity and future progression of CAC.. Adjusting for age and sex, IL-6 and leptin were associated with greater odds of increasing CAC severity (OR = 1.63, 95% CI 1.22-2.19; OR = 1.19, 95% CI 0.99-1.43, respectively, per SD). The association with IL-6 remained significant in models further adjusted for lifestyle, body size, CVD risk factors, and body fat distribution. Adiponectin was associated with CAC progression (OR = 0.68, 95% CI 0.51-0.92 in fully adjusted models). This was modified by sex, with protective effects seen for men (OR = 0.57, 95% CI 0.38-0.85), but not for women (OR = 0.93, 95% CI 0.67-1.32; p-for-interaction = 0.04).. IL-6 and leptin predicted greater CAC severity while adiponectin predicted lower odds of CAC progression. More research is needed to explore biological mechanisms, including differences by sex.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; California; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Disease Progression; Female; Humans; Interleukin-6; Leptin; Linear Models; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Risk Factors; Severity of Illness Index; Sex Factors; Time Factors; Tumor Necrosis Factor-alpha; Vascular Calcification

The internal thoracic artery (ITA) that differs from coronary artery (CA), rarely develops atherosclerosis. Understanding the mechanism underlying such a difference will help to pave a new way to the prevention and treatment of the disease. We hypothesize herein that the difference in susceptibility to atherosclerosis between CA and ITA is attributable to the heterogeneity of perivascular adipose tissues (PVATs) surrounding these two kinds of arteries, i.e. PVAT-CA and PVAT-ITA. We isolated PVAT from eight patients of coronary heart disease (CHD) and four non-CHD patients. Gene expression patterns were analyzed by using Agilent whole gene expression profile chips. By comparison between PVAT-CA and PVAT-ITA, we identified 2053 differentially expressed genes, of which 1042 were up-regulated and 1011 were down-regulated, respectively, in CHD group. KEGG pathway and gene ontology (GO) analysis revealed that those differentially expressed genes related to inflammation, lipid metabolism and myocardial processes were particularly noted in the CHD group, but not in non-CHD. Several selected genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), Toll-like receptor 2 (TLR2), Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), serum amyloid A2 (SAA2), and Leptin were validated by real-time PCR analysis. The results showed that the expression levels of IL-1β, IL-6, and Leptin were significantly higher in PVAT-CA than in PVAT-ITA (P = 0.016, 0.021, and 0.018) in CHD patients. Levels of TLR2, TIRAP, and SAA2 expression were also higher in PVAT-CA, however no significant difference was observed (P = 0.054, 0.092, and 0.058). In conclusion, our findings demonstrate differential gene expression patterns between PVAT-CA and PVAT-ITA, revealing a high heterogeneity in PVAT. Particularly, those genes related to inflammation, lipid metabolism and myocardial processes are differentially expressed in PVAT-CA and PVAT-ITA in CHD patients, suggesting an important role of PVAT in the development of coronary atherosclerosis.

Topics: Adipose Tissue; Aged; Coronary Artery Disease; Coronary Vessels; Female; Gene Expression Profiling; Humans; Leptin; Male; Mammary Arteries; Middle Aged; Toll-Like Receptor 2

Serum adipokines have roles in the development of arterial stiffness. Our aim was to investigate the relationship of leptin and the surrogate marker carotid-femoral pulse wave velocity (cfPWV) in coronary artery disease (CAD) patients.. Fasting blood samples were obtained from 105 CAD patients. cfPWV was measured with the SphygmoCor system. A cfPWV > 10 m/s was defined as high arterial stiffness, and ≤ 10 m/s as low arterial stiffness.. Thirty-seven patients (35.2 %) had high arterial stiffness, and had a higher percentage of diabetes (P = 0.001), hypertension (P = 0.010), older age (P = 0.001), and higher systolic blood pressure (SBP) (P < 0.001), diastolic blood pressure (DBP) (P = 0.021), pulse pressure (P = 0.014), and serum leptin level (P = 0.002) compared to patients with low arterial stiffness. Serum leptin levels correlated with the number of angiographically documented stenotic coronary artery vessels (P < 0.001). After adjusting for factors significantly associated with arterial stiffness, multivariate logistic regression analysis showed that leptin (odds ratio = 1.026, 95 % confidence interval: 1.002-1.051, P = 0.037) was a significant independent predictor of arterial stiffness.. Increasing serum concentration of leptin correlated positively with the total number of stenotic coronary arteries, and serum leptin level may predict the development of arterial stiffness in CAD patients.

Topics: Aged; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Cross-Sectional Studies; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Pulse Wave Analysis; Risk Factors; Severity of Illness Index; Up-Regulation; Vascular Stiffness

Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease.. 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay.. Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657).. Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target.

Topics: Adult; Aged; Aged, 80 and over; Angina, Stable; Biomarkers; Case-Control Studies; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Severity of Illness Index

The factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in 'cardiac' PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis.. Tissue specimens collected from male patients undergoing coronary artery bypass surgery were processed for real-time PCR, ELISA, in situ hybridization, and immunohistochemistry analysis. Leptin protein expression was elevated in C-PVAT compared to IMA-PVAT, independent of serum leptin levels. Compared to IMA-PVAT, C-PVAT exhibited more pronounced angiogenesis and inflammation, as indicated by significantly higher numbers of PECAM1-positive vessels and CD68-positive macrophages, and was characterized by a greater extent of fibrosis and hypoxia. Increased expression of hypoxia-inducible factor-1α and Fos-like antigen (FOSL)2, factors known to enhance leptin gene transcription, was observed in C-PVAT. As a proof of concept, exposure of human adipocytes to chemical hypoxia resulted in significantly increased FOSL2 and leptin mRNA levels.. A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

Topics: Adipocytes; Adipose Tissue; Aged; Angiogenic Proteins; Biomarkers; Cell Hypoxia; Cell Line, Tumor; Cellular Microenvironment; Coronary Artery Disease; Coronary Vessels; Culture Media, Conditioned; Fibrosis; Humans; Inflammation Mediators; Leptin; Male; Mammary Arteries; Middle Aged; Paracrine Communication; Plaque, Atherosclerotic; Prospective Studies; Up-Regulation

Clinical studies have demonstrated that adipocytokines play an important role in developing atherosclerotic cardiovascular diseases.. The aim of study was to evaluate the relationship between serum resistin and leptin levels with obesity and coronary artery disease (CAD).. In a cross-sectional study, we assessed the levels of serum resistin and leptin, C-reactive protein (CRP), lipid profile and cardiac enzyme tests (AST, CPK, LDH, CK-MB) in 40 CAD patients compared to 40 healthy controls. Anthropometric measurements including weight and height for calculating of body mass index (BMI), and waist circumference (WC) were performed for evaluation of obesity.. CAD patients had increased levels of leptin and CRP, (p < 0.001), cholesterol (p < 0.05), triglyceride (p < 0.01), and WC (p < 0.05) compared to healthy controls. There was no statistical difference between CAD and control subjects for resistin (p = 0.058). In a multiple regression analysis, only an association between serum leptin with BMI (β = 0.480, p < 0.05) and WC (β = 1.386, p < 0.05) was found.. The findings suggest that leptin is a better marker of fat mass value than resistin and may be considered an independent risk factor for cardiac disorders that is largely dependent on obesity. However, further prospective studies are needed to confirm these results.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anthropometry; Aspartate Aminotransferases; C-Reactive Protein; Case-Control Studies; Cholesterol; Coronary Artery Disease; Creatine Kinase; Cross-Sectional Studies; Female; Humans; L-Lactate Dehydrogenase; Leptin; Male; Middle Aged; Obesity; Reference Values; Regression Analysis; Resistin; Risk Factors; Statistics, Nonparametric; Triglycerides

To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque.. A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis.. (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P < 0.01). However, there was no significant difference (P > 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque volume (P < 0.05).. EATV is an independent risk factors of coronary heart disease and plaque vulnerability; EAT secretion of inflammatory cytokines from CHD patients is significant increased compared to NCHD patients, EAT secretion of inflammatory cytokines are positively correlated with EATV, both of which are determinants affecting vascular remodeling. Reducing EATV might help to attenuate inflammation and plaque vulnerability and reduce the risk of coronary heart disease.

Topics: Adipose Tissue; Angiography; Atherosclerosis; Calcinosis; Constriction, Pathologic; Coronary Artery Disease; Fibrosis; Humans; Leptin; Pericardium; Plaque, Atherosclerotic; Risk Factors; Tomography, X-Ray Computed

Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain.. We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient.. After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques.. In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.

Topics: Angina, Stable; Biomarkers; Cholesterol, HDL; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Humans; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Risk Factors; Tomography, X-Ray Computed; Vascular Calcification

Fat may accumulate around the heart in epicardial adipose tissue or inside the heart as lipid droplets (LDs).. To compare myocardial steatosis between subjects with and without coronary artery disease (CAD and non-CAD) and to identify which cells contain LDs.. Body mass index, waist circumference, glucose, insulin, homeostasis model assessment index, leptin, adiponectin, and high-sensitivity C-reactive protein were evaluated in CAD and non-CAD subjects. Biopsies were collected from right atrial myocardium. Immunohistochemistry for perilipin (PLIN) 1 and 2 was used to characterize LDs and their localization in adipocytes or myocardial cells, respectively. Cardiomyocytes apoptosis and hypoxia inducible factor 1 alpha were obtained in a subgroup of subjects.. The study took place in a hospital.. Male subjects consecutively undergoing elective cardiac surgery either for coronary bypass grafting (CAD, n = 23) or for valve replacement (non-CAD, n = 18).. The study was designed to compare myocardial steatosis between subjects with and without coronary artery disease.. PLIN1 and PLIN2 resulted significantly higher in CAD than in non-CAD subjects, as did apoptosis. PLIN1 was positively associated with circulating leptin, high-sensitivity C-reactive protein, and apoptosis, and negatively with adiponectin. PLIN2 was positively associated with body mass index, waist circumference, and leptin and negatively with adiponectin. After taking into account the absence/presence of hypertension, diabetes, and CAD/non-CAD, adiponectin was negatively associated with PLIN1 (r(2) = 0.532); waist circumference and adiponectin were associated with PLIN2 (r(2) = 0.399).. Myocardial steatosis is greater in CAD than non-CAD subjects, depending on both metabolically active adipocytes interspersed among cardiomyocytes and higher fat deposition inside cardiomyocytes; serum adiponectin and waist circumference are independent predictors of myocardial steatosis.

Topics: Adiponectin; Adipose Tissue; Aged; Body Mass Index; C-Reactive Protein; Carrier Proteins; Coronary Artery Disease; Humans; Insulin Resistance; Leptin; Male; Membrane Proteins; Middle Aged; Myocardium; Pericardium; Perilipin-1; Perilipin-2; Phosphoproteins; Waist Circumference

To investigate the correlation of CTRP9 with coronary atherosclerosis.. Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement).. Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (P < 0.05), but APN and CTRP9 were lower (P < 0.05). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C (P < 0.05) in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (P < 0.05). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (P < 0.05). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (P < 0.05).. Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD.

Topics: Adiponectin; Adipose Tissue; Aged; Coronary Artery Disease; Female; Gene Expression Regulation; Genetic Association Studies; Glycoproteins; Humans; Leptin; Male; Middle Aged; Pericardium; RNA, Messenger; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance, which is an important risk factor for coronary artery disease (CAD) and restenosis after coronary intervention. In this report, we set out to determine the role of the leptin-adiponectin ratio (LAR) in non-diabetic patients with or without impaired glucose tolerance undergoing a percutaneous coronary intervention.. 300 PCI patients were enrolled in this prospective single-centre study. Patients with known diagnosis of diabetes (n = 50) and newly diagnosed diabetes (2h OGTT > 200 mg/dL, n = 25) were excluded. In both stable and acute subjects, assessment was done on the day of discharge and included a fasting glucose level, leptin, adiponectin and an oral glucose tolerance test (OGTT).. LAR was significantly higher in diabetic (7.2 ± 0.7) than in non-diabetic patients (3.9 ± 0.3, P = 0.001), and even higher in newly diagnosed diabetics (9.8 ± 1.5, P < 0.001). Likewise, among non-diabetic patients, LAR was significantly higher in patients with impaired glucose tolerance. LAR was significantly higher in pre-diabetic (4.57 ± 0.48) versus normoglycaemic patients (3.45 ± 0.33, P = 0.05). LAR was found to be numerically higher in pre-diabetic versus normoglycaemic patients with two- and three-vessel disease (VD), but not in patients with single VD. In pre-diabetic patients, LAR was found to be significantly increased with more advanced CAD (P = 0.021), independent of stable versus unstable presentation.. LAR is related to the extent of CAD in pre-diabetic patients but not in normoglycaemic patients. This finding might in part explain the poorer outcome in revascularized patients with impaired glucose tolerance compared to normoglycaemic patients.

Topics: Adiponectin; Aged; Biomarkers; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Percutaneous Coronary Intervention; Prediabetic State; Preoperative Period; Prospective Studies; Risk Factors

To examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.. Nested cohort study.. We studied HIV-infected (HIV+) and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study with noncontrast computed tomography (CT) to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus, and cardiovascular disease (CVD) risk factors.. Significant findings were limited to adiponectin. HIV-positive men (n=493) had lower adiponectin levels than HIV-negative men (n=250) after adjusting for CVD risk factors (P<0.0001), which became nonsignificant after adjustment for abdominal visceral and thigh subcutaneous adipose tissue. Among HIV-positive men, lower adiponectin levels were associated with higher CD4 T-cell counts (P=0.004), longer duration of antiretroviral therapy (P=0.006), and undetectable HIV RNA levels (P=0.04) after adjusting for age, race, and CVD risk factors; only CD4 cell count remained significant after further adjustment for adipose tissue. In both groups, lower adiponectin levels were associated with increased odds of coronary stenosis more than 50% (P<0.007). Lower adiponectin levels were associated with increased extent of plaque in HIV-positive and of mixed plaque in HIV-negative men.. Adiponectin levels were lower in HIV-infected men and related to the severity of subclinical atherosclerosis, independent of traditional CVD risk factors.

Topics: Adiponectin; Adult; Aged; Angiography; Asymptomatic Diseases; Cohort Studies; Coronary Artery Disease; HIV Infections; Humans; Leptin; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed

Leptin and total homocysteine (tHcy) may participate in the pathogenesis of coronary artery disease (CAD) through nitric oxide (NO) depletion. We sought to investigate whether leptin, tHcy and NO are suitable predictors of CAD.. This study contained 50 control subjects and 50 stable and 50 unstable angina patients. Plasma leptin, tHcy and NO levels were determined using enzyme immunoassay, HPLC fluorescence and spectrophotometric methods, respectively. Other conventional risk factors were also determined.. Leptin and tHcy levels were highest in unstable angina patients, followed by stable angina patients and then controls (p < 0.001). Controls had significantly higher NO than patients (p <0.001). Leptin and tHcy had a positive and NO a negative association with the presence of CAD.. Some athrogenic effects of leptin may be mediated by affecting tHcy and NO levels. Plasma leptin, tHcy and NO levels showed significant contribution to CAD prediction and discrimination.

Topics: Aged; Angina, Stable; Angina, Unstable; Chromatography, High Pressure Liquid; Coronary Artery Disease; Female; Homocysteine; Humans; Immunoenzyme Techniques; Leptin; Male; Middle Aged; Nitric Oxide; Odds Ratio; Risk Factors; ROC Curve; Spectrometry, Fluorescence

The association of plasma adipokines beyond waist circumference (WC) with coronary artery calcification (CAC), a measure of subclinical atherosclerosis, is unknown.. Asymptomatic Caucasian individuals from two community-based cross-sectional studies (n = 1,285) were examined and multivariate analysis of traditional risk factors was performed, then WC and adipokines (adiponectin and leptin) were added. Incremental value of each was tested with likelihood ratio testing.. Beyond traditional risk factors, WC (Tobit regression ratio 1.69, P < 0.001) and plasma leptin (1.57, P < 0.001) but not plasma adiponectin (P = 0.75) were independently associated with CAC. In nested models, neither adiponectin (χ(2) = 0.76, P = 0.38) nor leptin (χ(2) = 1.32, P = 0.25) added value to WC beyond traditional risk factors, whereas WC added incremental value to adiponectin (χ(2) = 28.02, P < 0.0001) and leptin (χ(2) = 13.58, P = 0.0002).. In the face of important biomarkers such as plasma adiponectin and leptin, WC remained a significant predictor of CAC beyond traditional risk factors underscoring the importance of WC measurement during cardiovascular risk assessment.

Topics: Adiponectin; Adiposity; Adult; Aged; Calcinosis; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Waist Circumference; White People

Diabetic patients often exhibit severe, asymptomatic coronary artery disease (CAD). The relationship between osteoprotegerin (OPG), inflammatory markers and silent myocardial ischemia remains to be elucidated.. We recruited 45 type 2 diabetic patients and 33 healthy controls and assessed them for silent myocardial ischemia (SMI) by myocardial perfusion imaging. Patient blood was tested for OPG, IL-6 and leptin concentrations.. OPG, leptin and IL-6 levels were found significantly elevated in diabetic patients (p < 0.001, p < 0.01, p < 0.05). Based on our classification of presence/absence of SMI in our diabetic group, we found that there was a significant association between SMI and the biomarkers IL-6 (p < 0.001), leptin (p < 0.001) and OPG (p < 0.05). In multivariate regression analyses, OPG was found to be significantly related to diabetes mellitus and to SMI. Age, sex and smoking increased the association between OPG and SMI.. High OPG, leptin and IL-6 levels are associated with the presence and severity of SMI in type 2 diabetic patients.

Topics: Adult; Biomarkers; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Myocardial Perfusion Imaging; Osteoprotegerin; Regression Analysis

Overweight is related to higher levels of C-reactive protein (CRP) and leptin, which have been independently associated with increased risk for diabetes, cardiovascular disease, and the metabolic syndrome. Elevated CRP may trigger leptin resistance by inhibiting the binding of leptin to its receptors. We cross-sectionally examined the relationship between CRP, leptin, BMI z-score, percent body fat (%BF) assessed by air plethysmography (BodPod), and insulin sensitivity (SI) and acute insulin response (AIRg) measured by intravenous glucose tolerance test in 51 Latina and African-American females (77% Latina), mean age 9.2 (±0.9) years, at either Tanner Pubertal Stage (TPS) 1 (n = 25) or TPS 2 (n = 26). Females at TPS 2 had higher BMI z-scores, %BF (23% ± 10.1 vs. 30% ± 10.0, P = 0.02), AIRg (976.7 ± 735.2 vs. 1555.3 ± 1,223 µIU/ml, P = 0.05), fasting insulin (11.0 ± 10.8 vs. 17.2 ± 13.6 µlU/ml, P = 0.00) and leptin levels (11.0 ± 7.1 vs. 19.6 ± 10.9 ng/ml, P < 0.001) than those at TPS 1. There were no ethnic differences in any of the measured variables. CRP was positively correlated with BMI z-score (P = 0.001), %BF (P = 0.006), fasting insulin and AIRg (P = 0.02), and fasting leptin (P = 0.00), and negatively correlated with SI (P = 0.05). A linear regression model showed that CRP independently explained 10% (P = 0.00) of the variance in leptin after adjusting %BF, TPS, ethnicity, habitual physical activity and SI. Hence, low-grade inflammation may contribute to prolonged leptin exposure and leptin resistance, even in healthy children.

Topics: Adiposity; Analysis of Variance; Black or African American; Body Mass Index; C-Reactive Protein; Child; Coronary Artery Disease; Cross-Sectional Studies; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Leptin; Linear Models; Oxidative Stress; Puberty; Risk Factors; United States

Evidence suggests putative interactions of leptin and C-reactive protein (CRP) in the pathogenesis of adiposity-related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community-based cross-sectional studies coordinated at a single, university-based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log-transformed plasma leptin levels with higher CRP levels as defined by three cut-points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex-specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut-point (interaction term P values all <0.01 in fully adjusted models). Leptin levels were associated with CAC in those with high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in ln(leptin) (95% CI): 2.18 (1.29-3.66) if CRP level ≥3 mg/l; N = 461 vs. 0.94 (0.67-1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin-CRP interface in atherosclerosis risk.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Calcinosis; Calcium; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Risk Factors

In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance.. Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux.. Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P=0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (P<0.001), directly with arterial insulin concentration (P<0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P=0.044).. Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

Topics: ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Australia; Biological Transport; Cholesterol; Cholesterol Ester Transfer Proteins; Coronary Artery Disease; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Macrophages; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin-like growth factor-I(IGF-I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function.. The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram.. In 190 subjects (mean age, 54±11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51±10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the CPT. Associations between CPT%PDV and clinical parameters were analyzed.. According to multiple regression analysis, CPT%PDV was associated with plasma free IGF-I in the entire study population (β=0.295, P<0.001 in all subjects; β=0.341, P=0.001 in males; β=0.243, P=0.037 in females; β=0.303, P=0.002 in nonsmokers; and β=0.256, P=0.047 in smokers), and sCD40L in males (β=-0.269, P=0.008)and smokers (β=-0.261, P=0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF-I(6.9±3.3 vs 8.9±3.4, P=0.026) and CPT%PDV (8.8±24.9 vs 52.7±26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV.. Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF-I.

Topics: Adiponectin; Biomarkers; Blood Flow Velocity; CD40 Ligand; Chest Pain; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Echocardiography; Echocardiography, Doppler; Endothelium, Vascular; Female; Humans; Insulin-Like Growth Factor I; Leptin; Male; Regression Analysis

Our group has previously reported that visceral adipose tissue (VAT) accumulation was associated with the extent and vulnerable characteristics of coronary plaques using coronary computed tomography angiography (CTA). An investigation of the associations between these coronary lesions with plasma adiponectin and leptin was performed.. A total of 394 patients (220 men and 174 women) in the study were referred for CTA. Plain abdominal scanning was simultaneously performed to evaluate VAT areas. The median level of plasma high-molecular-weight (HMW) adiponectin in patients with CTA-based obstructive coronary artery disease was significantly lower than that in patients without (men: 1.45 vs. 1.88 µg/ml, P=0.002; women: 2.49 vs. 3.44 µg/ml, P<0.001). Multivariate analyses revealed that a lower HMW adiponectin concentration was significantly associated with the presence (men: P=0.019; women: P=0.018) and involved segment numbers (men: P=0.001; women: P=0.003) of coronary plaques. Furthermore, it was significantly related to coronary plaque with all 3 vulnerable characteristics of positive remodeling, low CT density (≤38 Hounsfield units), and adjacent spotty calcium (men: P=0.019; women: P=0.016). These associations were also observed with VAT areas, but not with plasma leptin concentrations, in both genders.. Lower plasma HMW adiponectin is associated with the presence, extent, and vulnerable characteristics of coronary plaques assessed by CTA in both genders.

Topics: Adiponectin; Adiposity; Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Female; Humans; Intra-Abdominal Fat; Japan; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Molecular Weight; Multivariate Analysis; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Severity of Illness Index; Tomography, X-Ray Computed

To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI) who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI) and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS) were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 ± 6.5 ng/ml.. The patients mean age was 50.5 ± 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI ≥ 30). Leptin concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after admission (mean ± SD) sample (1) =9.55 ± 7.4, sample (2) =12.9 ± 8.4, sample (3) =13.8 ± 10.4, sample (4) =18.9 ± 18.1, sample (5) =11.4 ± 6.5, sample (6) =10.8 ± 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p = 0.03). Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p ≤ 0.01). Significant correlation of mean serum leptin with the ejection fraction (P < 0.05) was found. No difference in timing of peak serum leptin between patients who achieved coronary reperfusion vs. those who did not (p = 0.8). There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the hospitalization nor at 9 months follow up.. Serum leptin levels increase after myocardial infarction. Serum leptin level may be a predictor of the left ventricular ejection fraction and the degree of atherosclerosis but not of coronary reperfusion.

Topics: Acute Disease; Adult; Body Mass Index; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Creatine Kinase; Echocardiography; Female; Fibrinolytic Agents; Humans; Leptin; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Risk Factors; Treatment Outcome; Ventricular Function, Left

The study's purpose was to investigate if physical activity initiated with the start of high-fat feeding would oppose development of endothelial dysfunction, and if it does, then to determine some potential mechanisms. C57BL/6 female mice were randomly divided into three groups: (1) control low-fat diet (LF-SED; 15% of calories from fat), (2) high-fat diet (HF-SED; 45% of calories from fat), and (3) HF diet given access to a voluntary running wheel (HF-RUN). Our hypothesis was that HF-RUN would differ in multiple markers of endothelial dysfunction from HF-SED after 10 weeks of 45%-fat diet, but would not differ from LF-SED. HF-RUN differed from HF-SED in nine determinations in which HF-SED either had decreases in (1) acetylcholine (ACh)-induced and flow-induced vasodilatations in isolated, pressurized coronary arterioles, (2) heart phosphorylated endothelial nitric oxide synthase (p-eNOS/eNOS) protein, (3) coronary arteriole leptin (ob) receptor protein, (4) phosphorylated signal transducer and activator of transcription 3 (p-STAT3/STAT3) protein, and (5) coronary arteriole superoxide dismutase 1 protein; or had increases in (6) percentage body fat, (7) serum leptin, (8) coronary arteriole suppressor of cytokine signalling 3 (SOCS3) protein, and (9) coronary arteriole gp91(phox) protein. Higher endothelium-dependent vasodilatation by ACh or leptin was abolished with incubation of NOS inhibitor N(G)-nitro-l-arginine-methyl ester (l-NAME) in LF-SED and HF-RUN groups. Further, impaired ACh-induced vasodilatation in HF-SED was normalized by apocynin or TEMPOL to LF-SED and HF-RUN. These findings demonstrate multiple mechanisms (eNOS, leptin and redox balance) by which voluntary running opposes the development of impaired coronary arteriolar vasodilatation during simultaneous high-fat feeding.

Topics: Animals; Arterioles; Coronary Artery Disease; Coronary Vessels; Diet, High-Fat; Disease Models, Animal; Endothelium, Vascular; Female; Leptin; Mice; Mice, Inbred C57BL; Motor Activity; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphorylation; Running

Body fat is an important source of adipokines not only in association with energy balance, but also with inflammatory and immune responses. This study investigated the relationship between serum levels of adipokines and coronary artery aneurysm in patients with Kawasaki disease (KD). Levels of leptin, adiponectin, and resistin were measured in 165 cases, including 4 groups: the control group (n = 85), KD with normal coronary arteries (n = 41), KD with dilatation and/or ectasia (n = 31), and KD with coronary aneurysm (n = 8). White blood cells counts (WBC), red blood cells counts (RBC), hemoglobin (HB), Hematocrit (Hct), platelet count, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were tested in children. Levels of adiponectin and resistin levels were significantly elevated; hemoglobin significantly decreased in the group of KD with coronary aneurysm compared with the controls or other KD subgroups. There were markedly positive relationships between levels of resistin and CRP, and negative relationships between levels of resistin and RBC in patients with KD. Levels of adiponectin, resistin, and hemoglobin were associated with the development of coronary aneurysm in children with KD. The up-regulation of resistin secreted from adipose tissue may be closely linked to up-regulation of systemic proinflammatory markers in acute KD.

Topics: Adiponectin; Adipose Tissue; Child, Preschool; Coronary Artery Disease; Female; Hematocrit; Hemoglobins; Humans; Infant; Leptin; Leukocyte Count; Male; Mucocutaneous Lymph Node Syndrome; Platelet Count; Predictive Value of Tests; Resistin; Vasculitis

Adiponectin and leptin link metabolic disorders and coronary artery disease (CAD). We analysed their relationship with CAD, classical risk factors and biomarkers in 287 CAD patients (cases) and 477 unaffected family members (controls) selected from the Indian Atherosclerosis Research Study (IARS). Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity markers. Novel biomarkers were measured according to manufacturer recommendations. Adverse clinical events were recorded through telephonic follow-up. Cases showed lower adiponectin levels (4684.62 ± 190.73 ng/ml) than controls (5768.86 ± 152.87 ng/ml) (p=1.58X10(-5)); Leptin levels were higher in affected males (12.47 ± 1.32 ng/ml) than in male controls (9.53 ± 1.19 ng/ml, p=0.017). Adiponectin 1st quartile showed significant protection against CAD in females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01, p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin levels. Adipokines showed opposing association trend with lipids, inflammatory and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity markers. Cases with recurrent event and controls who developed new cardiac event during follow up showed high adiponectin levels (p<0.05). A model that combined adiponectin, leptin and conventional risk factors yielded the best 'C' index (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed relatively poor survival curve as compared to the bottom Adiponectin tertile group. In conclusion, our findings strengthen the reported association between low adiponectin, high leptin, obesity-related metabolic disturbances and incident CAD in Asian Indians.

Topics: Adiponectin; Adult; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Female; Humans; India; Leptin; Male; Metabolic Syndrome; Middle Aged; Models, Cardiovascular; Obesity; Prognosis; Risk Factors

Obesity's association with hand osteoarthritis cannot be fully explained by mechanical loading. We examined the relationship between adipokines and radiographic hand osteoarthritis severity and pain.. In a pilot study of 44 hand osteoarthritis patients (39 women and 5 men), serum adipokine concentrations and hand x-ray Kallman-scores were analyzed using linear regression models. Secondary analyses examined correlates of hand pain.. The cohort had a mean age of 63.5 years for women and 72.6 for men; mean (standard deviation) Kallman-scores were 43.3(17.4) for women and 46.2(10.8) for men. Mean body-mass-index was 30 kg/m(2) for women and men. Mean leptin concentration was 32.2 ng/ml (women) and 18.5 ng/ml (men); mean adiponectin-total was 7.9 ng/ml (women) and 5.3 ng/ml (men); mean resistin was 7.3 ng/ml (women) and 9.4 ng/ml (men). No association was found between Kallman-scores and adipokine concentrations (R(2) = 0.00-0.04 unadjusted analysis, all p-values>0.22). Secondary analyses showed mean visual-analog-scale pain of 4.8(2.4) for women and 6.6(0.9) for men. Leptin, BMI, and history of coronary artery disease were found to be associated with visual-analog-scale scores for chronic hand pain (R(2) = 0.36 unadjusted analysis, p-values≤0.04).. In this pilot study, we found that adipokine serum concentrations were not associated with hand osteoarthritis radiographic severity; the most important correlates of joint damage were age and disease duration. Leptin serum concentration, BMI, and coronary artery disease were associated with the intensity of chronic hand OA pain.

Topics: Age Factors; Aged; Body Mass Index; Cohort Studies; Coronary Artery Disease; Female; Hand; Humans; Insect Hormones; Leptin; Linear Models; Male; Middle Aged; Musculoskeletal Pain; Oligopeptides; Osteoarthritis; Pyrrolidonecarboxylic Acid; Radiography; Resistin

Leptin is an adipokine with both protective and harmful effects on the cardiovascular (CV) system. Prior studies evaluating the association between leptin and CV outcomes have yielded conflicting results. Thus, we sought to investigate the relationship between leptin and CV events and mortality in patients with chronic stable coronary artery disease (CAD).. We performed a prospective cohort study of 981 outpatients with stable CAD. Leptin levels were measured in fasting venous samples at baseline. We used proportional hazards models to evaluate the association of baseline leptin with subsequent CV events (myocardial infarction, stroke, transient ischemic attack) and death.. During a mean follow-up of 6.2±2.1 years, there were 304 deaths, 112 myocardial infarctions, and 52 strokes/TIAs. In models adjusted for age, sex, and race, low leptin was associated with a 30% increased risk of the combined outcome (HR 1.30, CI 1.05-1.59, p=0.01). After further adjustment for obesity, traditional CV risk factors and biomarkers, low leptin remained associated with a 37% increased risk of events (HR 1.37, CI 1.06-1.76, p=0.02).. Low leptin is associated with increased CV events and mortality in patients with stable coronary artery disease. This association is independent of known factors affecting leptin levels, including gender and obesity.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Coronary Artery Disease; Down-Regulation; Female; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Leptin; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; San Francisco; Stroke

Multidetector row computed tomography (MDCT) enables the accurate noninvasive assessment of coronary artery stenosis and plaque imaging. The characteristics of patients who have coronary artery disease (CAD) as assessed by MDCT coronary computed tomography (CT) are not well known. Participants consisted of 513 consecutive patients with suspected CAD who underwent coronary CT. The authors quantified patient characteristics, including the prevalence of hypertension (HTN), hyperlipidemia and diabetes mellitus (DM), visceral fat area (VFA) and subcutaneous fat area using CT, and plasma levels of metabolic factors, including adiponectin and leptin. Although plasma levels of adiponectin in men and leptin in women were significantly associated with chronic kidney disease, there were no differences in these levels between patients with and without CAD. HTN was most significantly associated with the presence of CAD by multivariate logistic regression analysis (men, P=.002; women, P=.048). Finally, the percentage of CAD significantly increased as systolic blood pressure increased (trend, P=.0002) in men but not women. In conclusion, hypertension was significantly associated with CAD as assessed by coronary CT.

Topics: Adiponectin; Aged; Body Mass Index; Coronary Artery Disease; Cross-Sectional Studies; Female; Health Status Indicators; Humans; Hypertension; Japan; Leptin; Logistic Models; Male; Middle Aged; Prevalence; Risk Assessment; Risk Factors; Systole; Tomography, X-Ray Computed

The association of adipocyte-derived proteins, adiponectin and leptin, with the degree of coronary atherosclerosis has not been not been well elucidated. This study aimed to determine the relationship between serum adiponectin and leptin with the presence and degree of coronary atherosclerosis.. Seventy patients and 20 matched controls were recruited. Angiographic evaluation of coronary atherosclerosis was carried out by assessing three atherosclerotic indices, severity (transverse disease), extent (longitudinal disease), and pattern (lesion complexity).. The independent predictors of atherosclerosis severity were larger waist/hip ratio, followed by higher low-density lipoprotein-cholesterol, low serum adiponectin level, older age, higher leptin level, current unstable angina, and finally previous myocardial infarction (MI). This model is a good one as indicated by the model-adjusted r (50%). For extent index, lower serum adiponectin level was by far the most important independent predictor, followed by higher low-density lipoprotein-cholesterol, older age, and previous MI, whereas higher serum leptin level was only a univariate predictor. The model-adjusted r was 65%. For pattern index, the independent predictors were previous MI, lower serum adiponectin level, larger waist/hip ratio, higher serum leptin level, older age, and higher fasting blood glucose level. The model-adjusted r was 62%.. Both serum adiponectin and leptin might play an important pathogenic role not only in the occurrence but also in the severity, extent, and lesion complexity in coronary artery disease patients.

Topics: Adiponectin; Adult; Aged; Case-Control Studies; Coronary Artery Disease; Female; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index

Metabolic syndrome (MS) is associated with an increased risk of coronary artery disease (CAD) and type 2 diabetes mellitus (DM). In MS, adipose tissue has been shown to function as a paracrine and an endocrine organ secreting various adipocytokines. In the current study, adiponectin, tumor necrosis factor-α (TNF-α) and leptin gene expressions in the epicardial adipose tissue (EAT), paracardial adipose tissue (PAT) and subcutaneous adipose tissue (SAT) were investigated in MS patients with CAD and in non-MS patients without CAD.. Thirty-seven patients with MS undergoing coronary artery bypass grafting due to CAD (MS group) and twenty-three non-MS patients without CAD undergoing heart valve surgery (control group) were recruited prospectively to the study. Relative gene expressions of adiponectin, TNF-α and leptin in EAT, PAT and SAT were compared between two groups of patients. Adiponectin gene expression in EAT and PAT were significantly lower in MS group compared to the control group (p<0.0001, p=0.04, respectively) while SAT adiponectin gene expression did not differ significantly (p=0.64). TNF-α and leptin gene expressions were found to be statistically significantly higher in EAT, PAT and SAT of the MS group (p<0.0001, for all).. Our results demonstrate that TNF-α and leptin gene expressions increase prominently in the EAT, PAT and SAT while adiponectin gene expression decreases significantly in EAT and PAT in MS patients with CAD. These findings suggest that disturbances in expression of adiponectin, TNF-α and leptin in EAT, PAT and SAT might play an important role in MS patients with CAD.

Topics: Adiponectin; Adipose Tissue; Aged; Case-Control Studies; Coronary Artery Disease; Female; Gene Expression; Humans; Leptin; Male; Metabolic Syndrome; Middle Aged; Pericardium; Prospective Studies; RNA, Messenger; Subcutaneous Fat; Tumor Necrosis Factor-alpha

Topics: Atherosclerosis; Cardiovascular Diseases; Caveolin 1; Coronary Artery Disease; Endothelial Cells; Female; Humans; Leptin; Male

Topics: Adipose Tissue; Coronary Artery Disease; Female; Humans; Leptin; Male; Metabolic Syndrome; Tumor Necrosis Factor-alpha

Because of the strong association between abdominal obesity (AO) and other cardiovascular risk factors, it has been difficult to determine which changes in vascular function are directly related to this condition. Our objective was to evaluate the changes in ex-vivo vascular reactivity, circulating levels of adipokines and inflammatory markers associated with the presence of AO in subjects who underwent coronary artery bypass graft (CABG) controlling by the presence of other cardiovascular risk factors.. Subjects scheduled for a CABG with (n=17) and without (n=17) AO (defined as a waist circumference > or =90 cm for male or > or =80 cm for female) whom were matched by several cardiovascular risk factors, were included in the study. Lipid profile and plasma levels of glucose, insulin, leptin, adiponectin and inflammatory markers were measured. Internal mammary artery segments were used for ex-vivo vascular reactivity experiments and morphometry.. Leptin concentrations were higher and adiponectin concentrations were lower in subjects with AO. No differences were observed in other biochemical or clinical parameters between the groups. No correlation between waist circumference, HOMA index and inflammatory markers were observed. Endothelium-dependent relaxation to acetylcholine was lower, and contractile responses to angiotensin-II were higher in subjects with AO. These changes were not related to differences in vascular morphometry.. In subjects with severe coronary disease, the presence of AO was associated with leptin/adiponectin imbalance, decreased endothelium-dependent relaxation and an enhanced response to angiotensin-II. These changes occurred independently of other cardiovascular risk factors including insulin resistance and levels of inflammatory markers.

Topics: Adiponectin; Biomarkers; Blood Glucose; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Male; Mammary Arteries; Middle Aged; Multivariate Analysis; Obesity, Abdominal; Risk Factors; Severity of Illness Index; Vasoconstriction

Epicardial adipose tissue (EAT) is an interesting visceral fat pad with a particular location. EAT and subcutaneous adipose tissue (SAT) produce a wide range of adipokines. Some of them, including adiponectin and leptin, can influence the risk of development of diabetes and other associated metabolic and cardiovascular conditions. We sought to assess whether EAT and SAT adiponectin and leptin expression levels are different in diabetic patients with respect to nondiabetic subjects.. We collected samples of EAT from 120 patients and samples of SAT from 88 of the same group of patients undergoing elective cardiac surgery for coronary artery bypass grafting (n=69) or other procedures (n=51). After RNA isolation, adiponectin and leptin expression levels were analyzed by real-time reverse transcriptase PCR. Plasma levels were determined in small subsamples of subjects. Baseline clinical and treatment data were obtained from medical records.. A total of 45 diabetic and 75 nondiabetic subjects were included in the study. Mean (s.d.) age was 70.1 (7.8) years and there were 32% women. EAT and SAT adiponectin and leptin mRNA expression levels were similar in the diabetic and the nondiabetic groups (EAT adiponectin 14.4 (4.3) vs 14.6 (3.4) arbitrary units (a.u.), P=0.79; SAT adiponectin 15.6 (4.7) vs 15.1 (3.9), P=0.54; EAT leptin 9.3 (interquartile range 2.5) vs 9.5 (1.9) a.u., P=0.72; SAT leptin 9.9 (3.6) vs 10.0 (2.5) a.u., P=0.96). These findings persisted after stratification for sex and coronary artery disease. Logistic regression models including possible confounders and a combination of diabetes and impaired fasting glucose as a dependent variable led to similar results. Plasma adiponectin levels were lower in diabetic patients, whereas leptin levels showed a nonsignificant trend.. Diabetic and nondiabetic subjects express similar EAT and SAT adiponectin and leptin levels. Counter-regulatory mechanisms of adiponectin and leptin expression in patients with established diabetes might partly account for these findings.

Topics: Adiponectin; Adipose Tissue; Aged; Blotting, Western; Confidence Intervals; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Gene Expression; Humans; Leptin; Male; RNA, Messenger

The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA.. The coronary calcium score, homeostatic model assessment for insulin resistance (HOMA-IR) index, and serum adipocytokine (leptin, adiponectin, resistin, and visfatin) concentrations were determined in 169 patients with RA. The independent effect of each adipocytokine on insulin resistance according to the HOMA-IR index and on coronary artery calcification determined by electron beam computed tomography was assessed in models adjusted for age, race, sex, body mass index (BMI), traditional cardiovascular risk factors, and inflammation mediators. In addition, an interaction analysis was performed to evaluate whether the effect of the HOMA-IR index on the coronary calcium score is moderated by adipocytokines.. Increased concentrations of leptin were associated with a higher HOMA-IR index, even after adjustment for age, race, sex, BMI, traditional cardiovascular risk factors, and inflammation mediators (P < 0.001), but concentrations of visfatin (P = 0.06), adiponectin (P = 0.55), and resistin (P = 0.98) showed no association with the HOMA-IR index. None of the adipocytokines was independently associated with the coronary calcium score (all P > 0.05). Serum leptin concentrations showed a significant interaction with the HOMA-IR index (P for multivariate interaction = 0.02). Increasing leptin concentrations attenuated the increased risk of coronary calcification related to insulin resistance. Serum concentrations of the other adipocytokines showed no significant interactions with the HOMA-IR index (each P > 0.05).. Leptin is associated with insulin resistance in patients with RA but, paradoxically, attenuates the effects of insulin resistance on coronary calcification.

Topics: Adipokines; Adiponectin; Arthritis, Rheumatoid; Calcinosis; Calcium; Coronary Artery Disease; Cytokines; Female; Humans; Inflammation Mediators; Insulin Resistance; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Prevalence; Resistin; Risk Factors

It has been reported that alcohol stimulates appetite. We aimed to establish the association between leptin, as a major food intake regulating factor, and alcohol intake in patients with chronic manifest coronary artery or cerebrovascular disease.. A cross-sectional study of 820 subjects after acute coronary syndrome, coronary revascularization or after first ischemic stroke (the Czech part of EUROASPIRE III surveys). Leptin concentrations were evaluated among predefined categories of reported weekly alcohol intake: abstainers, light drinkers (up to 2 drinks weekly, 1-44 g of pure alcohol), mild regular drinkers (3-14 drinks weekly, 45-308 g) and moderate or heavy drinkers (more than 15 drinks, ≥ 309 g of alcohol).. Leptin showed a clear negative trend among the alcohol intake categories. Mild regular drinkers showed significantly lower leptin levels (9.3(8.2) ng/ml) compared with abstainers (18.7(18.7) ng/ml, P<0.0001) and light occasional drinkers (14.2(17.8) ng/ml, P=0.00064). The negative association between leptin and alcohol intake as a dependent variable remained significant even after adjustment for potential confounders in multiple linear regression analysis (P=0.00032).. Drinking of small amounts of alcohol was, in our setting, associated with decreased serum leptin concentration, with a possible benefit in terms of cardiovascular risk.

Topics: Aged; Alcohol Drinking; Cerebrovascular Disorders; Coronary Artery Disease; Cross-Sectional Studies; Ethanol; Female; Humans; Leptin; Male; Middle Aged; Risk Factors

Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA).. Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System.. There were 176 patients; 68% were male, mean age = 50 +/- (SD) 11 years, mean apnea/hyponea index (AHI) = 22.9 +/- 22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%) = 5.4% +/- 15, and mean body mass index (BMI) = 32.2 +/- 8 kg/m(2). In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin.. We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.

Topics: Adult; Coronary Artery Disease; Cytokines; Female; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Oxygen; Polysomnography; Reference Values; Risk Factors; Sleep Apnea, Obstructive; Vascular Cell Adhesion Molecule-1

The relationship between plasma leptin and insulin resistance among coronary artery disease (CAD) subjects remains poorly understood. We determined plasma leptin levels in insulin-resistant and insulin-nonresistant CAD patients. We also examined the association of plasma leptin with several cardiometabolic risk factors in all of the study group subjects from an Asian Indian population.. We evaluated 130 subjects among the Asian Indian population. Out of these, 65 were CAD subjects and 65 were age- and sex-matched, healthy, non-CAD controls. Fasting plasma levels of leptin, insulin, glucose, homocysteine, fibrinogen, and lipid parameters were estimated for all the subjects. Body mass index (BMI) and waist circumference (WC) were also determined.. We observed raised levels of leptin as well as homocysteine, BMI, and WC among the insulin-resistant CAD subjects compared to the insulin-nonresistant CAD subjects. Similarly, a significant elevation in plasma leptin, homocysteine, BMI, and WC was observed among the insulin-resistant controls compared to the insulin-nonresistant controls. Plasma leptin in CAD patients was correlated significantly with overall and abdominal obesity, insulin resistance, and insulin levels. However, it was nonsignificantly correlated with plasma homocysteine, fibrinogen, mean arterial pressure, and dyslipidemia in CAD subjects. On multiple regression analysis, we observed that raised plasma leptin in CAD was significantly associated with insulin resistance independent of obesity.. Our data showed a signifcant association of plasma leptin levels with insulin resistance in CAD that was independent of obesity.

Topics: Adult; Asian People; Body Mass Index; Coronary Artery Disease; Female; Fibrinogen; Glucose; Homocysteine; Humans; India; Insulin; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Risk Factors; Waist Circumference

Metabolic syndrome and coronary artery disease (CAD) are increasing in urban black South Africans during their transition from a rural to a western lifestyle. Inflammation is frequently associated with metabolic syndrome and CAD. This study evaluated markers of inflammation in black CAD patients, some of whom had metabolic syndrome.. Metabolic syndrome was defined according to International Diabetes Federation criteria. Inflammatory markers leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured in 40 patients and 20 control subjects.. Metabolic syndrome was present in 23 patients and absent in 17 patients. Leptin was the only significantly higher marker in patients with metabolic syndrome compared to patients without metabolic syndrome (P < 0.01). Leptin was higher in women than men (P < 0.01) and higher in both genders with metabolic syndrome (P < 0.03 and P < 0.04, respectively). Leptin levels rose significantly with increasing metabolic syndrome criteria (P < 0.05). hs-CRP concentrations were elevated in both patient groups. Positive correlations were found between leptin and body mass index (BMI) (r = 0.7107; P < 0.0001), waist circumference (WC) (r = 0.4981; P <0.002), and hs-CRP (r = 0.3886; P < 0.02).. Leptin differentiated between CAD patients with and without metabolic syndrome and determined metabolic syndrome status in women and men. Leptin was the only marker that increased with additional metabolic syndrome criteria. Elevated hs-CRP concentrations may indicate a low-grade inflammatory state in CAD patients. Association of leptin with BMI, WC, and hs-CRP revealed a close link with metabolic syndrome, obesity, and inflammation in urban black South African CAD patients.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Fasting; Female; Humans; Inflammation Mediators; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Sex Characteristics; South Africa; Urban Population; Waist Circumference

Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology.. Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified.. Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques).. Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis.

Topics: Aged; C-Reactive Protein; Chemokines; Cholesterol; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Resistin; Triglycerides; Tumor Necrosis Factor-alpha

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Resistin; Risk Factors

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 +/- 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and >or= 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 +/- 82.1 pg/mL) in patients with CFR >or= 2 were significantly higher than those in patients with CFR< 2 (63.3 +/- 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 +/- 37.81 ng/mL vs. 63.95 +/- 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Topics: Adolescent; Adult; Aged; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Endothelium, Vascular; Female; Ghrelin; Humans; Kidney Failure, Chronic; Leptin; Male; Microcirculation; Middle Aged; Peritoneal Dialysis; Ultrasonography; Young Adult

We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary artery calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma C-reactive protein (CRP).. Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease.. We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of Coronary Atherosclerosis).. Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance, and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjustment for age, gender, traditional risk factors, and Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor-2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, metabolic syndrome, and CRP.. In SIRCA, although both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.

Topics: Adipokines; Adiposity; Adult; Aged; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Risk Assessment; Risk Factors

Leptin has been linked to adiposity, insulin resistance, and coronary artery disease (CAD). We examined whether the leptin concentrations are associated with the risk of CAD and metabolic syndrome (MS). The plasma leptin concentrations were measured in 556 diabetic patients (341 men and 215 women). The odds ratio (OR) of CAD and MS were increased on moving from the lowest quartile (Q1) of leptin concentration to the highest quartile (Q4) and remained significant after adjusting for age, sex, BMI, concentrations of total cholesterol, triglyceride, or high-sensitivity C-reactive protein (hsCRP), and treatment modalities for hyperglycemia. The frequency of CAD was highest in the insulin resistant group (Q4 of homeostasis model assessment-insulin resistance index [HOMA-IR]) at Q4 of leptin concentration (34.5%), compared with that of Q4 of leptin (26.4%) or HOMA-IR (21.9%). In multivariate analysis, plasma leptin concentration was identified as the most significantly independent predictor for CAD (OR 10.24, 95% CI 3.01 to 45.05). Other variables with associated with CAD were age, sex, hypertension, low-HDL cholesterolemia, and hsCRP. In conclusion, hyperleptinemia might be an independent risk factor for CAD and MS in diabetic subjects. And the simultaneous measurement of insulin resistance and leptin concentration might be helpful for screening subjects with a high-risk of CAD.

Topics: Adult; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Odds Ratio; Prevalence; Risk Factors

Rheumatoid arthritis (RA) is a multisystem disease with high rates of morbidity and mortality. In recent years, there has been increasing focus on the growing rates of cardiovascular disease (CVD) in RA, over and above expected levels allowing for 'traditional' risk factors. In this paper the impact of CVD in RA, the relative contributions of traditional risk factors and novel risk factors (including homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin), and the need to address cardiovascular risk in the fight against premature death from coronary artery and stroke disease in RA are discussed.

Topics: Arthritis, Rheumatoid; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Comorbidity; Coronary Artery Disease; Endothelium, Vascular; Homocysteine; Humans; Leptin

Endothelial lipase (EL) is a plasma lipase that we previously reported to be significantly correlated with all features of the metabolic syndrome in humans, including directly with measures of adiposity and inversely with high-density lipoprotein cholesterol levels. We hypothesized that inflammation associated with obesity results in upregulation of EL. We determined the relationship between inflammatory markers and EL levels in a cohort of healthy persons recruited on the basis of family history of coronary disease. Furthermore, we directly tested the hypothesis that plasma EL concentrations would increase with induction of an inflammatory state by low-dose endotoxin in humans.. High-sensitivity C-reactive protein, interleukin 6, soluble tumor necrosis factor receptor II, soluble intercellular adhesion molecule 1, leptin, and adiponectin were measured in plasma of 858 subjects. Significant direct correlations (P<0.001 for all) were found between EL concentrations and high-sensitivity C-reactive protein (r=0.28), interleukin-6 (r=0.22), soluble tumor necrosis factor receptor II (r=0.22), soluble intercellular adhesion molecule 1 (r=0.24), and leptin (r=0.20). An inverse correlation was present with adiponectin (r=-0.15, P<0.001). Adiponectin inhibited the tumor necrosis factor-alpha-stimulated EL secretion from cultured human coronary endothelial cells in a dose-dependent manner. Experimental low-dose endotoxemia in 20 subjects resulted in a 2.5-fold increase in EL concentrations 12 to 16 hours after injection, which correlated temporally with decreases in both total and high-density lipoprotein phospholipid.. In humans, plasma inflammatory markers are directly correlated with plasma EL concentrations, and experimental endotoxemia significantly increases plasma EL concentrations, proving that EL is upregulated by inflammation in humans. This mechanism may partially explain the low high-density lipoprotein cholesterol levels seen in obesity and metabolic syndrome.

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Endothelium, Vascular; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Leptin; Lipase; Male; Middle Aged; Receptors, Tumor Necrosis Factor, Type II

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.

Topics: Adiponectin; Aged; Atherosclerosis; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Diabetes Complications; DNA; Female; Forearm; Gene Frequency; Genotype; Glucose Tolerance Test; Glycated Hemoglobin; Graft Occlusion, Vascular; Haplotypes; Humans; Hyperinsulinism; Leptin; Lipids; Male; Middle Aged; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Regional Blood Flow

Leptin is associated with adiposity and insulin resistance and may play a direct role in vascular calcification. It is unclear, however, whether leptin is an independent predictor of atherosclerotic burden.. The aim of this study was to examine the association between plasma leptin and coronary artery calcification (CAC) in an ethnically diverse cohort of older adult men and women free of clinical cardiovascular disease.. This was a cross-sectional study with data collection between January 2002 and February 2004 as part of the ADVANCE Study.. The study was conducted at an integrated health care delivery system in Northern California.. Participants included 949 men and women aged 60-69 yr old.. There were no interventions.. The main outcome measure was CAC by multidetector row computed tomography.. In ordinal logistic regression, plasma leptin levels were positively associated with extent of CAC independently of age, race/ethnicity, and smoking status in women (odds ratio of higher CAC for the sex-specific upper tertile vs. lower tertile = 1.81; 95% confidence interval, 1.10-3.00) but not in men (odds ratio = 1.29; 95% confidence interval = 0.89-1.86). However, this association was explained by metabolic risk factors and adiposity measures.. Our findings support a role of leptin on vascular calcification in women but, in our sample of older adults, the association between leptin and CAC was not independent of other cardiac risk factors.

Topics: Aged; Calcinosis; Cohort Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Risk Factors; Sex Distribution; Tomography, X-Ray Computed

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

The adipose tissue-related hormone leptin plays an important role in the regulation of body weight. The associations of leptin and leptin soluble receptor (sOb-R) with coronary artery disease (CAD) are not clear.. We measured leptin and sOb-R in 543 consecutive patients (379 men, 164 women) referred for coronary angiography for the evaluation of CAD. Coronary artery stenoses with lumen narrowing > or = 50% were considered significant.. Serum leptin correlated significantly with body mass index (r(s) = 0.443), with insulin resistance as assessed by the homeostasis model for the assessment of insulin resistance (r(s) = 0.339), with serum triglycerides (r(s) = 0.181), with systolic as well as diastolic blood pressure (r(s) = 0.170 and r(s) = 0.133, respectively) and, inversely, with sOb-R (r(s) = -0.346; P < 0.01 for all correlations). Coronary angiography revealed significant coronary artery stenoses in 331 (61%) of our patients. Serum leptin was significantly lower in patients with significant coronary artery stenoses than in patients without such lesions (8.5 +/- 7.8 vs. 13.2 +/- 12.2 ng mL(-1); P < 0.001). Multivariate logistic regression analysis proved serum leptin inversely and independently associated with the presence of significant coronary artery stenoses (standardized adjusted odds ratio 0.746, 95% confidence interval 0.566-0.983, P = 0.038). In contrast to serum concentrations of leptin, serum concentrations of sOb-R did not significantly differ between patients with significant stenoses and those without such lesions (22.4 +/- 8.3 vs. 23.1 +/- 12.1 ng mL(-1); P = 0.655).. Serum leptin but not sOb-R is significantly lower in patients with angiographically determined CAD. Despite its association with cardiovascular risk factors, leptin should not be simply regarded as a promoter of atherosclerosis.

Topics: Aged; Angiography; Body Mass Index; Cohort Studies; Coronary Artery Disease; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin; Regression Analysis; Risk Factors

The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation/oxidizability of apolipoprotein B-containing lipoproteins and several coronary artery disease risk factors, including homocysteine, high sensitive C-reactive protein, tumour necrosis factor-alpha, leptin and adiponectin in patients with schizophrenia. Oxidation of lipoproteins plays an important role in atherogenesis, and the enzyme paraoxonase has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity has been suggested to predict coronary artery disease. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum paraoxonase/arylesterase activities were determined spectrophotometrically. Malondialdehyde levels of apolipoprotein B-containing lipoproteins were determined before and after incubation with copper-sulphate, which yielded basal- and Delta-malondialdehyde values, respectively. Homocysteine and highly sensitive C-reactive protein levels were determined using a fluorescence-polarization immunoassay and immunonephelometry, respectively. Leptin and adiponectin levels were measured with radioimmunoassay and tumour necrosis factor-alpha was determined by enzyme linked immunosorbent assay. Serum paraoxonase and arylesterase activities were significantly lower and Delta-malondialdehyde levels were significantly higher in the schizophrenia group compared with the control group. However, there were not any significant differences in other parameters of the study between the study groups. There was a significant increase in body mass index and serum triglyceride and very low density lipoprotein cholesterol levels in the schizophrenic group after 6 weeks of treatment. These parameters were significantly increased in patients treated with atypical antipsychotics but not in patients treated with typic or long acting antipsychotics. The results of the present study suggest that patients with schizophrenia might have increased risk for coronary artery disease related to reduced serum paraoxonase activity and increased oxidizability of apolipoprotein B-containing lipoproteins.

Topics: Adult; Antipsychotic Agents; Aryldialkylphosphatase; C-Reactive Protein; Carboxylic Ester Hydrolases; Coronary Artery Disease; Female; Humans; Leptin; Lipoproteins; Male; Malondialdehyde; Oxidation-Reduction; Risk Factors; Schizophrenia; Triglycerides; Tumor Necrosis Factor-alpha

Fenofibrate, a selective (1)PPAR-alpha activator, is prescribed to treat human dyslipidemia. The aim of this study was to delineate the mechanism of fenofibrate-mediated reductions in adiposity, improvements in insulin sensitivity, and lowering of triglycerides (TG) and free fatty acids (FFA) and to investigate if these favorable changes are related to the inhibition of lipid deposition in the aorta. To test this hypothesis we used male LDLr deficient mice that exhibit the clinical features of metabolic syndrome X when fed a high fat high cholesterol (HF) diet. LDLr deficient mice fed HF diet and simultaneously treated with fenofibrate (100 mg/kg body weight) prevented development of obesity, lowered serum triglycerides and cholesterol, improved insulin sensitivity, and prevented accumulation of lipids in the aorta. Lowering of circulating lipids occurred via down-regulation of lipogenic genes, including fatty acid synthase, acetyl CoA carboxylase and diacyl glycerol acyl transferase-2, concomitant with decreased liver TG and cholesterol, and TG output rate. Fenofibrate also suppressed liver apoCIII mRNA levels and markedly increased lipoprotein lipase mRNA levels, known to enhance serum TG catabolism. In addition, fenofibrate profoundly reduced epididymal fat and mesenteric fat mass to the levels seen in lean mice. The reductions in body weight were associated with elevation of hepatic uncoupling protein 2 (UCP2) mRNA, a concomitant increase in the ketone body formation, and improved insulin sensitivity associated with tumor necrosis factor-alpha reductions and phosphoenol pyruvate carboxykinase down-regulation. These results demonstrate that fenofibrate improves lipid abnormalities partly via inhibition of TG production and partly via clearance of TG-rich apoB particles by elevating LPL and reduced apoCIII. The prevention of obesity development occurred via energy expenditure. Fenofibrate-mediated hypolipidemic effects together with improved insulin sensitivity and loss of adiposity led to the reductions in the aortic lipid deposition by inhibiting early stages of atherosclerosis possibly via vascular cell adhesion molecule-1 (VCAM-1) modulation. These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X.

Topics: Adiposity; Animals; Aorta; Coronary Artery Disease; Diet, Atherogenic; Energy Metabolism; Fenofibrate; Gluconeogenesis; Hypercholesterolemia; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Ligands; Lipid Metabolism; Lipids; Lipogenesis; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; PPAR alpha; Receptors, LDL; Triglycerides; Weight Gain

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Topics: Aged; Blood Glucose; C-Reactive Protein; Cholesterol; Coronary Artery Bypass; Coronary Artery Disease; Diabetic Angiopathies; Female; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Receptors, Interleukin-6; Receptors, Leptin; Risk Factors; Smoking; Vascular Cell Adhesion Molecule-1

We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease.. In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature.. Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.

Topics: Adult; Aged; Aged, 80 and over; Coronary Artery Disease; Dose-Response Relationship, Drug; Female; Humans; Leptin; Male; Mammary Arteries; Middle Aged; Nitric Oxide; Obesity; Saphenous Vein; Vasodilation; Vasodilator Agents

To determine serum leptin levels in patients with acute myocardial infarction (AMI) and coronary atherosclerosis (CS), and to analyze its correlation with C reactive protein (CRP), troponin T (TnT) and endothelin (ET).. Serum samples from confirmed AMI and CS patients were collected. Leptin and ET were assayed with high sensitive radioimmunoassay, TnT was determined with automatic biochemical analyser, and CRP was determined with enzyme-linked immunosorbant assay (ELISA).. Compared with normal control group, serum leptin, TnT, CRP and ET levels increased significantly (all P<0.01) in AMI patients. Serum levels of other cytokines, except TnT in CS patients, increased significantly compared with normal control group (all P<0.01). Correlation analysis showed that all the changes were not correlated with each other, each being an independent factor. Only serum TnT levels of AMI and CS patients showed a significant difference (P<0.01).. Serum leptin levels of both AMI and CS patients increase significantly without a significant difference between each other, and there is no correlation for leptin with CRP, TnT and ET.

Topics: C-Reactive Protein; Coronary Artery Disease; Endothelins; Humans; Leptin; Myocardial Infarction; Troponin T

Leptin signaling may promote atherothrombosis and lead to cardiovascular disease. However, whether leptin is associated with human atherosclerosis, distinct from thrombosis, is unknown. We determined the association of plasma leptin levels with coronary artery calcification (CAC), a measure of coronary atherosclerosis, in a cross-sectional study of type 2 diabetes. Leptin levels were associated with CAC after adjusting for established risk factors [odds ratio (95% confidence interval) for 5 ng/ml leptin increase: 1.31 (1.10-1.55); P = 0.002]. Leptin remained associated with CAC after further controlling for body mass index (BMI) [1.29 (1.07-1.55); P = 0.008], waist circumference [1.30 (1.09-1.57); P = 0.003], C-reactive protein (CRP) levels [1.28 (1.07-1.55); P = 0.008], and subclinical vascular disease [1.30 (1.08-1.57); P = 0.006]. Addition of BMI (P = 0.97), waist (P = 0.55), or CRP (P = 0.39) to a model with leptin failed to improve the model's explanatory power, whereas addition of leptin to a model with BMI (P = 0.029), waist (P = 0.006), or CRP (P = 0.005) improved the model significantly. Plasma leptin levels were associated with CAC in type 2 diabetes after controlling adiposity and CRP. Whether leptin signaling promotes atherosclerosis directly or represents a therapeutic target for the prevention of atherosclerotic cardiovascular disease remains to be explored.

Topics: Adult; Aged; Calcinosis; Coronary Artery Disease; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Leptin; Male; Middle Aged

This study was designed to evaluate the relationship between plasma leptin and prognosis in patients with angiographically confirmed coronary atherosclerosis.. Experimental studies suggest that leptin, an adipose tissue-derived hormone, exerts important cardiovascular effects.. Study subjects were recruited prospectively from a cohort of patients undergoing clinically indicated coronary angiography (n = 382). The median duration of follow-up was four years. Follow-up information was available for 361 patients.. The combined end point of cardiac death, myocardial infarction (MI), cerebrovascular accident, or re-vascularization occurred in 44 subjects. In the simple Cox model, leptin had a significant (p < 0.001) non-linear/cubic univariate relationship with the combined end point. Other variables associated with prognosis in the univariate analysis were body mass index (BMI), prior MI, insulin resistance, C-reactive protein (CRP), fibrinogen, and number of coronary vessels with >50% stenosis. A positive relationship between leptin and prognosis was also seen when leptin levels were split by quintiles, with a hazard ratio of 6.46 for the highest quintile. The only two variables significantly associated with the combined end point in the multivariate Cox model were leptin (p = 0.004) and number of coronary vessels with >50% stenosis (p < 0.001). A similar relationship between leptin and prognosis was observed when leptin was adjusted for BMI.. In patients with angiographically confirmed coronary atherosclerosis, leptin is a novel predictor of future cardiovascular events independent of other risk factors, including lipid status and CRP.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Coronary Artery Disease; Female; Fibrinogen; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Minnesota; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Statistics as Topic

The development and progression of coronary atherosclerosis is influenced by a variety of genetic and environmental factors. Among the genetic factors, the cell surface receptor LRP/A2MR (LDL receptor-related protein/alpha2-macroglobulin receptor) was shown to be involved in a variety of biological processes leading to atherosclerotic plaque formation. That is why the individual expression of this receptor may, therefore, be considered as an evident predictor for coronary atherosclerosis. In this clinical ex vivo study the expression was measured by competitive RT-PCR and macroarray analysis in native monocytes. Both methods were first tested in an in vitro model using different human cells and cell lines (fibroblasts: chorion, skin; endothelial cells from umbilical cord vein; monocyte cell line: Mono-Mac-6): after stimulation with an LRP/A2MR ligand, leptin, the anticipated direct effect of this ligand, namely an increase in both receptor mRNA and protein expression, was confirmed. In disease-related ex vivo studies the mRNA and protein-expression of LRP/A2MR was investigated in 36 male patients suffering from myocardial infarction. In comparison to the control group (36 healthy male blood donors), a significant up-regulation of mRNA was detected in the myocardial infarction patient group (control: 122.3 ag/cell versus patients: 223 ag/cell; P<0.001). Investigating the LRP/A2MR protein expression a significant down-regulation of protein expression was determined in the patient group (control: 6 pg/cell versus patients: 1.6 pg/cell; P<0.001). The ratio of LRP/A2MR mRNA and protein expression is obviously an evident marker for coronary atherosclerosis, recommendable for the assessment of the individual coronary risk profile.

Topics: Blood Donors; Case-Control Studies; Cell Line; Cells, Cultured; Coronary Artery Disease; Humans; Leptin; Low Density Lipoprotein Receptor-Related Protein-1; Male; Middle Aged; Myocardial Infarction; Receptors, LDL; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

While multiple growth factor, cytokines, and immune cells are identified in atherosclerotic lesions, as well as an essential nonneuronal function of neurotrophins implicated in cardiovascular tissue development and in lipid and glucose metabolism, the role of the neurotrophins NGF and BDNF and also the adipokine leptin in human coronary atherosclerosis and related disorders, such as metabolic syndrome, remains unclear. Here we report that (i) both the amount and the immunoreactivity of NGF was reduced and the expression of p75NGF receptor and the number of mast cell increased in human atherosclerotic coronary arteries (n = 12) compared with control specimens (n = 9) obtained from autopsy cases, and (ii) NGF and BDNF plasma levels were reduced in patients with metabolic syndrome (n = 23) compared with control subjects (n = 10). Also, in metabolic syndrome patients, a positive correlation between the plasma leptin levels and the number of adipose tissue mast cells was found, suggesting that leptin may be a novel adipoimmune mediator. Altogether, the results provide the first correlative evidence for the potential involvement of NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome, implying neuroimmune and adipoimmune pathways in the pathobiology of these cardiovascular disorders.

Topics: Brain-Derived Neurotrophic Factor; Coronary Artery Disease; Coronary Circulation; Female; Humans; Leptin; Male; Mast Cells; Metabolic Syndrome; Middle Aged; Nerve Growth Factor