leptin and Coronary-Disease

Although high leptin concentration has been shown to be correlated with established vascular risk factors, epidemiologic studies have reported inconclusive results on the association between leptin and cardiovascular diseases (CVD). Therefore, a meta-analysis was performed to evaluate this issue.. We searched Pubmed, Embase, and the Cochrane Library from their inception to Jan 2016 for both case-control and cohort studies that assessed leptin concentration and CVD risk. Reports with odds ratio (OR), risk ratio (RR) and corresponding 95% confidence intervals (CI) were considered. The data were extracted by two investigators independently.. A total of 13 epidemiologic studies totaling 4257 CVD patients and 26710 controls were included. A significant inverse association was shown between leptin and coronary heart disease (CHD), with an overall OR of 1.16 (95% CI: 1.02-1.32), but not for stroke (OR = 1.21, 95% CI 0.98-1.48) under sociodemographic adjustment. Further adjustment for additional cardiovascular risk factors resulted in ORs of 1.16 (95% CI 0.97-1.40) for CHD and 1.10 (95% CI 0.89-1.35) for stroke. The findings remained when analyses were restricted to high-quality studies and indicated OR estimates of 1.07 (95% CI 0.96-1.19) for CHD and 0.98 (95% CI 0.76-1.25) for stroke. In a subgroup meta-analysis, a high leptin level was not independently associated with CHD in both females (OR = 1.03, 95% CI 0.86-1.23) and males (OR = 1.09, 95% CI 0.95-1.26) or with stroke in both females (OR = 1.13, 95% CI 0.87-1.47) and males (OR = 0.80, 95% CI 0.59-1.09). There was no significant publication bias as suggested by Egger test outcomes.. Our findings indicate that high leptin levels may not be associated with risks of CHD and stroke. Further large, well-designed prospective cohort studies are needed to fully evaluate the role of leptin on the risk of CVD.

Topics: Coronary Disease; Humans; Leptin; Risk Factors; Stroke

Leptin, an adipose tissue-derived hormone, plays a central role in regulating human energy homeostasis. The role of leptin in regulating blood pressure, activating the sympathetic nervous system, insulin resistance, platelet aggregation, arterial thrombosis, angiogenesis, and inflammatory vascular responses suggests that leptin may have a close relationship with the development of coronary heart disease (CHD). However, no conclusive data are available to determine the association between leptin and CHD.. The PubMed, EMBASE and Cochrane databases were surveyed for original studies describing the association between leptin and CHD outcome from the date of publication of each database through March 2013. The data were extracted by two investigators independently.. The meta-analysis reported here was comprised of eight original articles with a total of 21,064 participants (10,842 men, 10,222 women) and 2053 CHD events. The odds ratio for the sociodemographic-adjusted study reported here was 1.57 (95% confidence interval, 1.14-2.16) and 1.72 (95% confidence internal, 1.03-2.87) in males and females, respectively. Further adjustment for additional cardiovascular risk factors resulted in an odds ratio of 1.36 (95% confidence interval, 0.98-1.88) in males and 1.50 (95% confidence interval, 0.93-2.42) in females. Sensitivity analysis restricted to sociodemographics-adjusted studies with high methodological quality indicated an estimate of 1.47 (95% confidence internal, 1.06-2.04) in males and 1.85 (95% confidence internal, 0.61-5.63) in females. Sensitivity analysis restricted to cardiovascular risk factor-adjusted studies showed no significant differences in both males and females.. The results of the meta-analysis represents the most precise and accurate estimate of the relationship between leptin and CHD. Although the associations of leptin and CHD were not statistically significant both in male and female overall, males with high levels of leptin should be paid more attention to. Our findings highlight the need for additional well-designed and gender-specific prospective studies to evaluate the role of leptin on the development of CHD.

Topics: Adult; Aged; Case-Control Studies; Cohort Studies; Coronary Disease; Female; Humans; Leptin; Male; Middle Aged; Obesity; Risk Factors; Sensitivity and Specificity

This study sought to better determine the link between leptin and coronary heart disease (CHD).. Circulating leptin is considered a risk factor for CHD but larger studies are needed.. Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis.. Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I(2) = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31).. Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.

Topics: Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol; Coronary Disease; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Random Allocation; Risk Factors; Triglycerides

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

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Coronary Disease; Diabetes Complications; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Potassium; Risk Factors; Vascular Resistance

Fatty tissue synthesizes and secretes a wide range of products that may be directly involved in the pathogenesis of the complications associated with obesity. These so-called adipokines may trigger or sustain a chronic inflammatory process. By manipulating the secretory function of fat cells, it might in future be possible to prevent the development of the metabolic and cardiovascular complications of obesity. Current data already suggest that weight reduction and certain substances with an anti-inflammatory action reduce the risk for the metabolic and cardiovascular complications of obesity. To date, however, the evidence available is only indirect, and is insufficient to definitively establish causal relationships between certain secretory products of adipocytes and the comorbidities of adiposity. Further clinical studies are needed.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Obesity; Plasminogen Inactivators; Risk Factors; Thromboembolism; Weight Loss

Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic lesions. Correlation between resistin concentration and the extent of atherosclerotic plaques in the coronary vessels has also been found. The disturbances in secretion, function and balance of adiponectin, leptin and resistin are to be considered not only a link between visceral adiposity and cardiovascular risk but also independent risk factor of coronary heart disease.

Topics: Adiponectin; Coronary Disease; Energy Metabolism; Humans; Intra-Abdominal Fat; Leptin; Resistin; Risk Factors

Insulin resistance syndrome is the theory that glucose intolerance, hyperinsulinemia, increased very low density lipoprotein triglyceride level, decreased high density lipoprotein cholesterol level, and hypertension are proposed consequences of insulin resistance. These metabolic disturbances have been shown to increase the risk of coronary artery disease. In this theory, insulin resistance and the resultant hyperinsulinemia are considered to raise blood pressure through 1) sympathetic nervous system activation, 2) renal sodium retention, 3) renin-angiotensin system stimulation, and 4) intracellular calcium accumulation in vascular smooth muscle. Indeed, metabolic disturbance and insulin resistance have been pointed out in essential hypertensives. Leptin is a recently discovered hormone produced by an adipocyte-specific ob gene, that contributes to the regulation of energy balance by informing the hypothalamus of the amount of adipose tissue in the body. As a result, the hypothalamus adjusts food intake, thermogenesis, and energy expenditure appropriately. It was clarified that ob gene expression and plasma leptin level in humans were highly correlated with the body mass index, insulin sensitivity and blood pressure. Thus, leptin could play a role in the pathophysiology of insulin-resistant hypertension.

Topics: Coronary Disease; Glucose Intolerance; Humans; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypothalamus; Insulin Resistance; Leptin; Risk; Syndrome

Atherosclerosis starts in childhood, and is accelerated in some individuals. A cluster of clinical and biochemical factors constitute the risk profile for many of them, perhaps most important being metabolic insulin resistance syndrome. Insulin resistance and its components for children and adolescents, especially obesity and dyslipidemia, are generators of hypertension, glucose intolerance and complications of atherosclerosis in adulthood. Some individuals are genetically predisposed, particularly those with the family history of such disorders. For many subjects, there is 'tracking' of metabolic and lifestyle factors from early age to adulthood. Several new risk factors of atherosclerosis (e.g. level of lipoprotein (a), procoagulant state, hyperhomocysteinemia, low birth weight and adverse in-utero environment, and possibly inflammatory markers) are current and potentially future areas of research concerning children and young individuals. Definition of and research on new and hitherto not investigated factors and formulation of strategies to neutralize the known factors are of paramount importance for primary prevention of atherosclerosis. Simple and effective measures for prevention include increasing awareness of the diseases, maintenance of ideal body weight, regular physical exercise, avoidance of smoking and chewing of tobacco, eating a balanced diet, and early periodic monitoring of blood pressure and metabolic status. These measures, starting from childhood, should be applied to all and in particular to the susceptible offspring, predisposed individuals, and populations.

Topics: Adolescent; Adult; Age Factors; Arteriosclerosis; Birth Weight; Blood Coagulation Factors; Child; Child, Preschool; Coronary Disease; Diabetes Complications; Exercise; Female; Homocysteine; Humans; Hypertension; Infant; Infant, Newborn; Insulin Resistance; Leptin; Life Style; Lipids; Lipoprotein(a); Male; Middle Aged; Obesity; Primary Prevention; Risk Factors; Sex Factors; Smoking

Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.

Topics: Animals; Arteriosclerosis; Coronary Disease; Diet; Exercise; Humans; Insulin Resistance; Leptin; Obesity; Proteins; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Alternate day fasting (ADF; ad libitum "feed day", alternated with 25% energy intake "fast day"), is effective for weight loss and cardio-protection in obese individuals. Whether these effects occur in normal weight and overweight individuals remains unknown. This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects.. Thirty-two subjects (BMI 20-29.9 kg/m2) were randomized to either an ADF group or a control group for 12 weeks.. Body weight decreased (P < 0.001) by 5.2 ± 0.9 kg (6.5 ± 1.0%) in the ADF group, relative to the control group, by week 12. Fat mass was reduced (P < 0.001) by 3.6 ± 0.7 kg, and fat free mass did not change, versus controls. Triacylglycerol concentrations decreased (20 ± 8%, P < 0.05) and LDL particle size increased (4 ± 1 Å, P < 0.01) in the ADF group relative to controls. CRP decreased (13 ± 17%, P < 0.05) in the ADF group relative to controls at week 12. Plasma adiponectin increased (6 ± 10%, P < 0.01) while leptin decreased (40 ± 7%, P < 0.05) in the ADF group versus controls by the end of the study. LDL cholesterol, HDL cholesterol, homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment.. These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached.

Topics: Adiponectin; Adult; Aged; Body Composition; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diet, Reducing; Energy Intake; Fasting; Female; Humans; Leptin; Male; Middle Aged; Overweight; Risk Factors; Surveys and Questionnaires; Triglycerides; Weight Loss

The ability of alternate-day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10-week trial with three consecutive dietary intervention phases: (i) 2-week baseline control phase, (ii) 4-week ADF controlled feeding phase, and (iii) 4-week ADF self-selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat-free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low-density lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High-density lipoprotein cholesterol (HDL-C), C-reactive protein, and homocysteine concentrations did not change. Decreases in LDL-C were related to increased adiponectin (r = -0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = -0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post-treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Biomarkers; Body Composition; Coronary Disease; Diet, Reducing; Fasting; Female; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Resistin; Risk Factors; Waist Circumference; Weight Loss

To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.. A nested case-control study examined circulating leptin and adiponectin levels in plasma obtained 4-6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events. The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis.. Relative risk (RR) increased across increasing leptin quartiles; the highest quartile compared with the lowest quartile was related to the highest risk (P for trend=0.002); the increased risk remained after adjustment for risk factors (P=0.018) or for obesity (P=0.038), but in the final model (adjusted for randomized treatment, other drugs, LIPID risk score, age and body mass index), the risk was attenuated (RR=1.61, 95% CI: 0.72-3.57, P for trend=0.34). Adiponectin did not predict cardiovascular events. Subjects randomly allocated to pravastatin had 6% lower leptin levels (P=0.04) than those allocated to placebo.. Plasma leptin was a significant and independent predictor of recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.

Topics: Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Coronary Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Pravastatin; Recurrence; Risk; Stroke

Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting.. Both patients with CHD undergoing coronary stenting (120 patients) and control subjects (58 patients) were submitted to an oral glucose tolerance test (OGTT). Fasting leptin levels and fasting and postglucose load insulin sensitivity were assessed. Endothelial function was measured by nitrite and nitrate release (NOx) during OGTT. More than 50% of patients treated with stent implantation presented impaired glucose tolerance or type 2 diabetes, which was previously undiagnosed. These patients also had higher glucose, insulin, and leptin levels than control subjects. Among the stented patients, insulin and leptin levels were higher in patients with restenosis than in patients without restenosis. A significant increase in NOx levels was found during OGTT both in patients without restenosis and in control subjects. On the contrary, NOx profiles were blunted in patients with restenosis. At multiple regression analysis, only DeltaAUC-NOx areas and insulin sensitivity index showed an independent correlation with the minimal lumen diameter at follow-up.. We demonstrated that insulin resistance and endothelial dysfunction are independent predictors of early restenosis after coronary stenting.

Topics: Area Under Curve; Blood Glucose; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Mellitus, Type 2; Endothelium, Vascular; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Nitric Oxide; Predictive Value of Tests; Regression Analysis; Stents; Vascular Patency

Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19.. Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit.. CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05).. In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

Topics: C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; COVID-19; Exercise; Fibrinogen; Galectin 3; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Pandemics; Risk Factors

Leptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation.. Leptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m. Observational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval.

Topics: Adipose Tissue; Cardiovascular Diseases; Carotid Intima-Media Thickness; Coronary Disease; Female; Humans; Leptin; Male; Mendelian Randomization Analysis; Middle Aged; Risk Factors

The aim of this study was to explore the association between the expression of adenosine monophosphate-activated protein kinase (AMPK) pathway and adiponectin (APN), leptin, and vascular endothelial function in rats with coronary heart disease (CHD).. Experimental rats were divided into three groups, including: control (Col) group, CHD model (CHD) group, and CHD+AMPK activator (CHD+AICAR) group. Except those in Col group, all rats were fed with high-fat diet and intraperitoneally injected with pituitrin to establish the CHD model. The levels of serum APN, leptin, and endothelin-1 (ET-1) were determined via enzyme-linked immunosorbent assay (ELISA). The content of serum nitric oxide (NO) was detected using the nitrate reductase method. Meanwhile, the expression of AMPK pathway-related protein AMPKα in vascular endothelial tissues was detected via Western blotting (WB). Aortic vascular endothelial cells (VECs) were cultured with AICAR or ET-1 in vitro. Subsequently, the expressions of AMPK pathway and protein kinase B (AKT) pathway-related proteins were determined through co-immunoprecipitation and WB. Moreover, the expression level of NO in VECs was determined using the DAF-FM DA fluorescence probe.. Compared with Col group, CHD group showed significantly decreased levels of serum APN and NO (p<0.05), significantly increased the levels of leptin and ET-1 (p<0.05), as well as remarkably decreased protein expression of p-AMPKα in vascular endothelial tissues (p<0.05). After injection of AMPK activator AICAR (200 mg/kg), the protein expression of p-AMPKα in CHD rats was significantly activated (p<0.05). The levels of serum APN and NO were remarkably upregulated (p<0.05), while the levels of leptin and ET-1 were significantly reduced (p<0.05). Besides, AICAR could evidently activate the activity of AMPK pathway in VECs in vitro, upregulate the protein levels of p-eNOS (Ser1177) and p-AMPKα, and promote the secretion of NO (p<0.05). In addition, AICAR remarkably inhibited ET-1-induced expression of AKT pathway (p<0.05).. Activating the AMPK pathway may play a positive role in the normal function of VECs and exert a certain curative effect on CHD in rats.

Topics: Adiponectin; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Cells, Cultured; Coronary Disease; Diet, High-Fat; Endothelium, Vascular; Gene Expression; Leptin; Rats; Rats, Sprague-Dawley; Ribonucleotides; Signal Transduction

Ageing and biological senescence, both related to cardiovascular disease, are mediated by oxidative stress and inflammation. We aim to develop a predictive tool to evaluate the degree of biological senescence in coronary patients.. Relative telomere length (RTL) of 1002 coronary patients from the CORDIOPREV study (NCT00924937) was determined at baseline in addition to markers of inflammatory response (hs-C-Reactive Protein, monocyte chemoattractant protein-1, IL-6, IL-1β, TNF-α, adiponectin, resistin and leptin) and oxidative stress (nitric oxide, lipid peroxidation products, carbonylated proteins, catalase, total glutathione, reduced glutathione, oxidized glutathione, superoxide dismutase and peroxidated glutathione). Biological senescence was defined using the cut-off value defined by the lower quintile of relative telomere length in our population (RTL = 0.7629). We generated and tested different predictive models based on logistic regression analysis to identify biological senescence. Three models were designed to be used with different sets of information.. We selected those patients with all the variables proposed to develop the predictive models (n = 353). Statistically significant differences between both groups (Biological senescence vs. Nonbiological senescence) were found for total cholesterol, catalase, superoxide dismutase, IL-1β, resistin and leptin. The area under the curve of receiver-operating characteristic to predict biological senescence for our models was 0.65, 0.75 and 0.72.. These predictive models allow us to calculate the degree of biological senescence in coronary patients, identifying a subgroup of patients at higher risk and who may require more intensive treatment.

Topics: Aged; Aging; C-Reactive Protein; Catalase; Cholesterol; Coronary Disease; Female; Humans; Inflammation; Interleukin-1beta; Leptin; Male; Middle Aged; Oxidative Stress; Randomized Controlled Trials as Topic; Resistin; Risk Assessment; Secondary Prevention; Superoxide Dismutase; Telomere

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60-64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60-64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60-64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships.

Topics: Adipocytes; Adiponectin; Biomarkers; Body Mass Index; C-Reactive Protein; Coronary Disease; E-Selectin; Endothelium; Female; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Proinsulin; Risk Factors; Smoking; Social Class; Socioeconomic Factors; Tissue Plasminogen Activator; United Kingdom

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

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

To estimate the association between patterns of alcohol consumption and biomarkers of coronary heart disease (CHD) risk.. Cross-sectional study among 10,793 individuals representative of the Spanish population aged ≥ 18 years. The threshold between moderate and heavy drinking was 40 g of alcohol/day in men and 24 g/day in women. Binge drinking was defined as intake of ≥ 80 g of alcohol in men and ≥ 60 g in women at any drinking occasion in the preceding 30 days. Analyses were performed with generalized linear models with adjustment for the main confounders, and results were expressed as the percentage change in the geometric mean (PCGM). Compared to non-drinkers, moderate and heavy drinkers had progressively higher serum HDL-cholesterol, with a PCGM ranging from 4.8% (95% CI: 3.7-6.0%) in moderate drinkers without binge drinking (MNB) to 9.6% (5.1-14.2%) in heavy drinkers with binge drinking (HB). Fibrinogen decreased progressively with alcohol intake, from -2.2% (-3.1 to -1.3%) in MNB to -5.8% (-9.4 to -2.0%) in HB. Leptin, glycated hemoglobin and the HOMA-index also decreased with increasing alcohol intake, and particularly with binge drinking.. Moderate alcohol intake is associated with improved HDL-cholesterol, fibrinogen and markers of glucose metabolism, which is consistent with the reduced CHD risk of moderate drinkers in many studies. Heavy and binge drinking were also associated with favorable levels of CHD biomarkers; since these drinking patterns produce substantial health harms, our results should not be used to promote alcohol consumption.

Topics: Adult; Aged; Alcohol Drinking; Alcoholic Intoxication; Biomarkers; Blood Glucose; Cholesterol, HDL; Coronary Disease; Cross-Sectional Studies; Female; Fibrinogen; Glycated Hemoglobin; Homeostasis; Humans; Insulin Resistance; Leptin; Linear Models; Male; Middle Aged; Risk Factors; Spain; Young Adult

Obesity is characterized by hyperleptinaemia, which is associated with diabetes, hypertension and coronary heart disease. The aim of this study was to determine if body fat and muscle measures predict the natural increase in leptin over 2·6 years in older adults.. A total of 190 subjects (50% females) aged between 50 and 79 years were selected to perform the serum measurements for leptin. Height and weight were measured and body mass index (BMI) was calculated. Fat and lean mass of the whole body and the trunk were acquired through dual-energy X-ray absorptiometry (DXA). Leg muscle strength and handgrip strength were measured using dynamometry.. In multivariable analyses, leg muscle strength was negatively associated with both baseline leptin (β: -0·05 μg/l per kg, 95% CI: -0·08, -0·02) and follow-up leptin (β: -0·04 μg/l per kg, 95% CI: -0·07, -0·01). BMI, and percentage total fat and trunk fat and their respective change per annum (cpa) were significantly and positively associated with leptin. Lean mass was negatively associated with baseline leptin. Gender-specific analyses produced similar associations between leg muscle strength, fat measures and follow-up leptin in males and females.. Besides positive associations between body fat, trunk fat and leptin, we found that leg muscle strength was negatively associated with leptin after 2·6 years in a sample of older population. This suggests that interventions to maintain or increase muscle strength may have a protective effect on hyperleptinaemia.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Body Mass Index; Coronary Disease; Female; Hand Strength; Humans; Hypertension; Leptin; Male; Middle Aged; Muscle Strength

The aim of this study was to investigate the associations of adiponectin and leptin with metabolic syndrome (MetS) and coronary heart disease (CHD) in patients with various coronary risk factors. We determined serum adiponectin, leptin, and metabolic syndrome components in 104 patients (59 men and 45 women; aged 40-86 years) with various coronary risk factors at a cardiovascular out-patient clinic. Natural logarithmic transformed (ln) leptin was lower in men and smokers, and positively correlated with body mass index (BMI) (r = 0.59, P < 0.0001), waist circumference (r = 0.60, P < 0.0001), and homeostasis model assessment of insulin resistance (HOMA-IR) levels (r = 0.24, P < 0.02). Ln adiponectin was higher in women and nonsmokers, and was correlated with age and high-density lipoprotein cholesterol (HDL-C). Patients with MetS (n = 69) had significantly higher BMI, HOMA-IR, and ln leptin and lower ln adiponectin than those without Mets (Ln leptin, 2.14 ± 0.08 versus 1.30 ± 0.11; Ln adiponectin, 2.29 ± 0.06 versus 2.54 ± 0.09). In contrast, patients with coronary heart disease (CHD: n = 40) had significantly lower serum ln adiponectin concentrations than non-CHD patients (n = 64) (1.79 ± 0.12 versus 1.91 ± 0.10) as well as lower HDL-C and a higher smoking percentage. Consistent results were obtained by multivariate analyses. In conclusion, this study disclosed factors associated with the increase in serum leptin and adiponectin. Serum levels of leptin may be associated positively with MetS, whereas adiponectin levels are associated negatively with MetS and CHD, even in patients with various coronary risk factors.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Algorithms; Analysis of Variance; Biomarkers; Body Mass Index; Coronary Disease; Female; Humans; Leptin; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Outpatients; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Waist Circumference

Adiponectin and leptin are adipose tissue-derived hormones, shown to have opposing associations with the metabolic syndrome and coronary heart disease (CHD). This study evaluated the association between the leptin/adiponectin ratio and the components of the metabolic syndrome in a cohort with CHD. Methods and results This cross-sectional study included data from 105 subjects (men = 91), undergoing first-time elective coronary artery bypass grafting (CABG). Leptin and adiponectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Association was found between the leptin/adiponectin ratio and homeostatic model assessment (HOMA) (r(s) = 0.34, P = 0.0006), fasting insulin concentrations (r(s) = 0.37, P = 0.0001), fasting glucose concentrations (r(s) = 0.24, P = 0.01), systolic blood pressure (r(s) = 0.20, P = 0.05), diastolic blood pressure (r(s) = 0.24, P = 0.02), waist circumference (r(s) = 0.55, P < 0.0001), body mass index (BMI) (r(s) = 0.55, P < 0.0001) and waist/hip ratio (r(s) = 0.38, P = 0.0001). A significant difference was found in ratios between those with and without insulin resistance (HOMA > 3 and HOMA ≤ 3) (P = 0.029) and those with and without metabolic syndrome, defined by the International Diabetes Federation, (P < 0.001). However, using receiver operating characteristic (ROC) analysis and assessment of area under curve (AUC), the leptin/adiponectin ratio did not perform significantly better than its components.. In patients with severe CHD, the leptin/adiponectin ratio was not found to be a robust tool to distinguish patients with and without insulin resistance and those with and without the metabolic syndrome.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Statistics as Topic; Waist Circumference; Waist-Hip Ratio

To analyze the influence ofhyperleptinemia on fasting lipid and hematological parameters in healthy Arab male youth in Jordan, this cross-sectional study was carried out in April 2009 on a sample of 120 students aged 18-24 years. Subjects were stratified by fasting leptin into two groups (control, <12.7 ng mL(-1) vs. hyperleptenimic, e_< 12.7 ng mL(-1)) and BMI (normal weight, < 25 kgm(-2) vs. overweight/obese, BMI e_< 25 kg m(-2)). Fasting serum leptin, blood glucose, lipid profile and hematological parameters values were determined by standard kit methods. Mean serum leptin concentrations were more than five times as high in hyperleptenemic subjects than in control subjects (p < 0.001). Compared with control group, significant elevations (p < 0.01) were observed in the means total cholesterol, LDL cholesterol and triglyceride levels of hyperleptenemic group whereas no significant differences was detected in HDL-cholesterol. Except the changes of WBC count, MCH and slightly MCHC, there were no differences between both groups in any other term of hematological parameters. In conclusion, changes in lipid variables and some hematological parameters may increase plasma viscosity as a step during atherosclerosis pathogenesis in male youth at risk for dyslipidemia and cardiovascular diseases. Thus, hyperleptinemia could be a useful index in identifying healthy youth male subjects but this hypothesis needs further investigation.

Topics: Adolescent; Arabs; Blood Cell Count; Cholesterol; Cholesterol, LDL; Coronary Disease; Cross-Sectional Studies; Erythrocyte Indices; Humans; Jordan; Leptin; Lipids; Male; Risk Factors; Triglycerides; Young Adult

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

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

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

Recent researches have shown that adipocytokines secreted by adipose tissue play an important role in inflammation which is considered to be a crucial step in the pathogenesis of atherosclerosis. Leptin, one of the earlier adipocytokines, is known to play a major role in cardiovascular disease and recent observations suggest that leptin is an independent risk factor for coronary heart disease. Resistin, another recently discovered adipocytokine, has been related to risk factors of atherosclerosis, and in diabetic individuals serum resistin levels correlate well with inflammatory markers and are predictive for the development of cardiovascular disease. Adiponectin, another adipocytokine of interest in recent years, seems to be the most promising one studied to date. In contrast to leptin and resistin, adiponectin seems to be beneficial for health and it is a protective factor and decreased in obesity. However, many other factors derived from adipose tissue have also been discovered, such as interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, apelin, visfatin and probably others awaiting discovery in the near future. In this paper, we discussed the role of adipocytokines in the pathogenesis of atherosclerotic cardiovascular disease.

Topics: Adiponectin; Coronary Disease; Humans; Leptin; Risk Factors; Thromboembolism

To examine the association of increased plasma leptin concentration with prevalent stroke and coronary heart disease (CHD) and to examine the genetic contributions of leptin to this association in the Jackson Heart Study cohort.. A cohort of 5170 participants aged 21-84 years who underwent Exam I during 2000-2004 was analysed. Odds ratios (OR) of prevalent stroke and CHD were calculated using a logistic regression model adjusted for age, smoking, hypertension and waist circumference (WC). Variance component analysis was used to partition the phenotypic variance of leptin into the polygenic and environmental components.. The prevalence of stroke and CHD was 4.04% and 5.85% in women, and 4.88% and 8.92% in men, respectively. Body mass index (BMI) and WC were highly correlated with leptin both in men and women. In multivariate analysis stratified by sex, leptin was significantly associated with stroke (OR = 1.97, 95% CI = 1.21-3.21) in women after adjustment for age, smoking, systolic blood pressure, BMI and WC (P = 0.0079). No significant association was observed in men. Heritability of sex-, age-adjusted log-transformed leptin for this cohort was 38.0% and 37.8% after further adjustment for WC and hypertension, respectively. In addition, a sibship effect was also found to be significant and explained 12.2% of the total variance of leptin (P = 0.007).. There is a significant association of leptin with stroke in women, which is partly influenced by the genetic factor. The findings suggest that leptinemia is an independent risk factor for stroke in African American women.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Mississippi; Prevalence; Risk Factors; Stroke; Up-Regulation; Young Adult

Despite modulating a number of metabolic processes linked to atherosclerosis, including glucose regulation, hematopoiesis, fatty acid catabolism and angiogenesis, the potential association of adiponectin and leptin with coronary heart disease is still a matter of controversy.. We conducted a population-based case-cohort study within the MONICA/KORA Augsburg studies. Serum levels of adipokines were measured in 333 case subjects with incident CHD and 1,728 non-case subjects selected from a source population of 9300 middle-aged men and women. Mean follow-up was 10.8+/-4.6 years. We sought to analyze the association of leptin and adiponectin and their ratio with CHD.. After adjustment for various confounding factors the hazard ratios and 95% confidence intervals comparing tertile extremes were 0.79 (0.53-1.17) for leptin (top vs bottom tertile) and 0.87 (0. 62-1.23) for adiponectin (bottom vs top tertile), respectively. Furthermore, the ratio of leptin/adiponectin also showed no association with CHD (HR 1.01 (0.68-1.51)).. The present study reports the association of leptin and adiponectin with incident CHD in a large population-based cohort. In contrast to fairly strong associations previously reported, our findings indicate no clinically relevant association between leptin, adiponectin and their ratio with the risk of CHD after adjustment for potential confounders.

Topics: Adiponectin; Cohort Studies; Coronary Disease; Female; Germany, West; Humans; Incidence; Leptin; Male; Middle Aged; Risk

An increase of FVII activity (FVIIc) has been proposed to be an independent cardiovascular risk factor. Whether FVII is associated with insulin resistance in coronary heart disease (CHD) is still unknown. We tested the hypothesis that plasma FVII activity and leptin are associated with insulin resistance independently.. We studied 130 subjects, of which 65 were CHD subjects and 65 were non-CHD control subjects. Fasting plasma levels of leptin, insulin, glucose, FVIIc activity, fibrinogen, lipid parameters were estimated for all the subjects. Body mass index (BMI), waist circumference (WC) and blood pressure levels were also determined.. We observed significantly raised plasma levels of FVIIc activity, leptin and insulin resistance among the CHD subjects compared to the non-CHD subjects. Raised FVIIc activity levels in CHD were significantly positively correlated with insulin resistance. Raised plasma leptin levels in CHD were correlated with insulin resistance, BMI and WC. Multivariate regression analysis showed that elevated levels of FVII activity in CHD was significantly associated with insulin resistance, independent of dyslipidemia, leptin, blood pressure levels, BMI, WC, gender and age. Furthermore, raised leptin levels in CHD subjects were significantly associated with insulin resistance and BMI, independently of each other and of dyslipidemia, FVIIc, blood pressure levels, WC, gender and age.. Raised FVII and leptin levels in CHD patients were independently associated with insulin resistance, this was not observed among the non-CHD subjects.

Topics: Adult; Coronary Disease; Factor VII; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged

Adipokines play an important role in glucose, lipid and lipoprotein metabolisms, as well as in coagulation and inflammatory processes. So far, studies have evaluated the association of individual adipokines with future coronary heart disease (CHD) event and provided mixed results.. We sought to investigate the association of a set of adipocytokines, including total adiponectin, adipsin, resistin, leptin and plasminogen activator inihibitor-1 (PAI-1), with future CHD events in apparently healthy men.. We built a nested case-control study within the PRIME Study, a multicenter prospective cohort of 9779 healthy European middle-aged men. Total adiponectin, adipsin, resistin, leptin and PAI-1 were measured in the baseline plasma sample of 617 men who developed a first CHD event (coronary death, myocardial infarction, stable or unstable angina) during 10 years of follow-up and in 1215 study-matched controls, by multiplex assays using commercial kits. HRs for CHD were estimated by conditional logistic regression analysis.. Median concentrations of total adiponectin, adipsin and resistin were similar in cases and in controls, whereas those of leptin and PAI-1 were higher in cases than in controls, 6.30 vs 5.40 ng ml(-1), and 10.09 vs 8.48 IU ml(-1), respectively. The risk of future CHD event increased with increasing quintiles of baseline leptin and PAI-1 concentrations only in unadjusted analysis (P-value for trend <0.003 and <0.0001, respectively). However, these associations were no longer significant after adjustment for usual CHD risk factors including hypertension, diabetes, smoking, total cholesterol, triglycerides and HDL cholesterol. Conversely, baseline CRP and IL-6 levels remained associated with CHD risk in multivariate analysis.. In apparently healthy men, circulating total adiponectin, adipsin, resistin, leptin and PAI-1 were not independent predictors of future CHD event.

Topics: Adipokines; Adiponectin; Biomarkers; Case-Control Studies; Coronary Disease; Humans; Interleukin-6; Leptin; Life Expectancy; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Prospective Studies; Resistin; Risk Factors; Surveys and Questionnaires

The goal of this study was to investigate the effects of simvastatin on the levels of plasma leptin and nitric oxide (NO) in patients with coronary heart disease (CHD). The study population consisted of 65 patients with CHD and 48 control individuals without signs or symptoms of CHD. The patients with CHD were treated with simvastatin 20mg/day. Fasting serum lipids, leptin and NO were determined before and after 12 weeks of treatment. Leptin levels were higher in patients with CHD than control (P<0.05). Statin treatment significantly decreased plasma lipids and leptin levels and increased NO concentration in all CHD patients (P<0.05). Serum leptin levels after treatment correlated negatively with the NO concentration (P<0.05). Simvastatin may provide beneficial effects of reducing leptin levels, independent of its lipid-lowering action, which may play an important role in patients with CHD.

Topics: Aged; Coronary Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Lipids; Male; Middle Aged; Nitric Oxide; Simvastatin

Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.. 81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.. Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.. Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.

Topics: Adult; Aged; alpha-2-HS-Glycoprotein; Biomarkers; Blood Proteins; C-Reactive Protein; Calcifediol; Calcinosis; Comorbidity; Coronary Disease; Diabetic Nephropathies; Disease Progression; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Risk Factors; Rome; Severity of Illness Index; Survival Analysis; Tomography, Spiral Computed

Topics: Aged; Aging; Biomarkers; Cause of Death; Coronary Disease; Follow-Up Studies; Humans; Leptin; Logistic Models; Male; Predictive Value of Tests; Survival Analysis; Testosterone

Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR.. The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations.. Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant.. There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.

Topics: Adiponectin; Aged; Cohort Studies; Coronary Disease; Female; Glomerular Filtration Rate; Humans; Kidney; Leptin; Male; Middle Aged; Multivariate Analysis; Resistin; Risk Factors

Prospective studies have shown a positive association between leptin concentrations and coronary heart disease (CHD) in men, but its effect in women is unclear. Our objective was to examine the association of serum leptin levels with CHD in a prospective study of women.. We conducted a prospective (4 year) case (N=165) control (N=335) study nested within a cohort of 4286 British women.. With mutual adjustment for each other and age, social class, smoking, and physical activity, leptin was positively associated with BMI, fasting insulin, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and hypertension and was inversely associated with homeostasis model assessment insulin sensitivity. Leptin was not associated with CHD risk (age-adjusted relative risk for a doubling of leptin: 1.08 [95% confidence interval (CI): 0.91, 1.29]). This changed little with adjustment for childhood and adult social class, smoking, alcohol, and physical activity but attenuated to 1.00 (95% CI: 0.80, 1.26) with further adjustment for other metabolic risk factors (waist-to-hip ratio, low-density lipoprotein-cholesterol, triglycerides, C-reactive protein, fasting insulin, hypertension).. We found no strong statistical evidence that leptin is associated with CHD risk in this study population of older British women. Further research is needed to compare associations of leptin with CHD in men and women and to determine whether the effect varies by gender.

Topics: Aged; Alcohol Drinking; Body Mass Index; Case-Control Studies; Cohort Studies; Coronary Disease; Exercise; Fasting; Female; Humans; Leptin; Prospective Studies; Sex Characteristics; Smoking; Social Class; United Kingdom

Leptin and insulin have been reported to be risk factors for coronary heart disease (CHD) in the general population, but their role in type 2 diabetes still remains unclear.. The role of leptin and insulin upon CHD in type 2 diabetes was assessed in 154 patients, aged 31-77 years, who were treated with oral anti-diabetic agents. Multivariate logistic regression analyses were used with CHD (an established history of CHD or an abnormal treadmill test) as dependent, and leptin, insulin and potential confounders as independent variables.. Endogenous insulin was significantly associated with CHD in a model controlling for gender, age, duration of diabetes, body mass index, smoking and leptin (Odds ratio 1.45 per decile, 95% confidence interval 1.11-1.90). Improving control for confounding by replacing body mass index by subcutaneous fat (CT-measured at the L4-L5 level) and height in this model, resulted in a significant negative association between leptin and CHD (OR 0.60, 95% CI 0.37-0.96).. Leptin might have a beneficial effect on CHD in type 2 diabetes, probably by counteracting the effect of insulin-like molecules or insulin resistance. The effect was elucidated only after careful control for confounding by subcutaneous fat, the main source of leptin production.

Topics: Adult; Aged; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Leptin; Male; Middle Aged

High-density lipoprotein (HDL) has significant anti-atherogenic properties, whereas the underlying mechanisms are complex and have not been completely elucidated. Adipocytes produce a variety of adipokines with cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to the increased risk of atherosclerosis associated with obesity. Clinical evidences indicate that higher plasma HDL-C levels are associated with a favourable adipokines secretion profile, suggesting that HDL might improve the dysregulated adipokines secretion. HDL may diminish lipid accumulation in adipocytes through phosphorylation of PPARgamma and inhibition of aP2 expression, which possibly account for the favourable effects of HDL on adipokines secretion. Therefore, we hypothesize that HDL might exert several beneficial effects on adipocytes, which may relate to its anti-atherogenic properties.

Topics: Adipocytes; Adipokines; Adipose Tissue; Adult; Aged; Atherosclerosis; Cholesterol, HDL; Coronary Disease; Female; Humans; Leptin; Lipoproteins, HDL; Male; Middle Aged; Risk Factors

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.

Topics: Adenosine Diphosphate; Aged; Angina, Unstable; Blood Platelets; Coronary Disease; Female; Flow Cytometry; Humans; Leptin; Male; Myocardial Infarction; P-Selectin; Prolactin

The study was designed to examine the effect of percutaneous coronary intervention (PCI) on adiponectin and leptin levels. We have previously demonstrated that PCI triggers a systemic inflammatory response. We hypothesized that inflammation participates in the pathogenesis of diabetes mellitus and the metabolic syndrome by modulating levels of adiponectin and leptin.. Prospective study in which inflammation was induced by PCI.. Forty-eight patients with stable coronary artery disease and without diabetes mellitus.. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), leptin and adiponectin were measured at baseline and 48 h after the procedure.. Following PCI, hs-CRP increased by 211%, IL-6 by 87% and leptin by 19%, while adiponectin decreased by 14% (P < 0.001 for all). The change in IL-6 correlated with that in hs-CRP (rho = 0.32; P = 0.027), as did the changes in IL-6 and leptin (rho = 0.31; P = 0.03). The change in adiponectin, however, did not correlate with the change in any of the other markers.. This study demonstrates that PCI affects the levels of adiponectin and leptin within 48 h. These effects may be secondary to the inflammatory response triggered by PCI.

Topics: Adiponectin; Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Disease; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Postoperative Period; Prospective Studies; Statistics, Nonparametric

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

Topics: Adult; Aged; Body Mass Index; Cholesterol; Coronary Disease; Female; Fibronectins; Humans; Hypertension; Leptin; Male; Middle Aged; Smoking; Thrombosis; Tissue Plasminogen Activator; Vitronectin

Topics: Adiponectin; Adipose Tissue; Coronary Disease; Diabetes Mellitus, Type 2; Endocrine Glands; Humans; Leptin; Lipids

Relative increases in unsaturated fatty acids (USFA) in the diet are considered to exert beneficial effects on coronary risk factors (CRF). However, detailed analysis of the relationships between serum USFA and CRF are scanty and there is no report of the relationship between nervonic acid (NA) and CRF. The objective of the present study was to analyze the relationships between serum USFA and CRF. Body height and weight, blood pressure, fasting serum total cholesterol (TC), triacyl-glycerol (TG), HDL cholesterol (HDLc), fasting blood sugar (FBS), total fatty acid composition, leptin, and high-sensitivity C-reactive protein (CRP) were measured in 31 men (age, 41-78 years) and 11 women (age, 54-77 years). The relationships between serum USFA, and body mass index (BMI), leptin, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, HDLc, FBS, and CRP were analyzed using multiple regression analysis. The final results were summarized using coronary risk factor scores (CRFS) in order to assess the correlations between USFA with CRF. Oleic acid (OA), linoleic acid (LA), and eicosapentaenoic acid (EPA) were positively related to coronary risk factors (total CRFS = 2, 3, and 4, respectively), while nervonic acid (NA) exerted negative effects on these risk factors (total CRFS = -6 ). It is concluded NA may have preventive effects on obesity-related metabolic disorders.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Coronary Disease; Cross-Sectional Studies; Eicosapentaenoic Acid; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Humans; Leptin; Linoleic Acid; Male; Middle Aged; Obesity; Oleic Acid; Regression Analysis; Risk Factors

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

Epidemiological studies demonstrate a relation between preeclampsia (PE) and an increased risk of maternal coronary heart disease (CHD) in later life. However, there are few data available to explain any underlying mechanism. We recruited 40 primigravid women with a history of proteinuric PE delivering between 1975 and 1985 and 40 controls, matched as a group for time of index pregnancy, smoking, and current body mass index to assess classic (lipids, blood pressure) and novel (adhesion molecules, insulin, leptin) risk factor pathways. Women with a history of PE had higher diastolic blood pressure compared with controls (83 vs 76 mm Hg, P<0.05), but there were no significant differences in fasting lipoprotein concentrations (P>0.20). However, concentrations of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1) in particular were higher in the PE group by 14% (P=0.038) and 44% (P=0.002), respectively. The cases also demonstrated a tendency toward higher fasting insulin (P=0.08) concentrations and had higher glycosylated hemoglobin levels (P=0.004). Leptin concentrations were not significantly elevated. Interestingly, significantly more of the women with history of PE were classified as menopausal (37.55% vs 17.5%, P=0.045). The differences in ICAM-1 concentration persisted (P=0.010) after adjustment for potential confounders, including hormonal use/menopausal status, antihypertensive or lipid-lowering therapy, and social class. We conclude that classic risk factors alone cannot fully explain the elevated CHD risk in women with a history of PE. Rather markedly elevated ICAM-1 concentrations and specific but subtle features of the metabolic syndrome (glucose, blood pressure) are likely to be involved.

Topics: Adult; Biomarkers; Blood Pressure; Cell Adhesion Molecules; Coronary Disease; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Leptin; Lipoproteins; Middle Aged; Pre-Eclampsia; Pregnancy; Risk Factors

Topics: Body Mass Index; Coronary Disease; Female; Humans; Hypercholesterolemia; Leptin; Lipid Metabolism; Lipids; Male; Nutritional Physiological Phenomena; Obesity; Risk Factors

To compare plasma leptin in Saudi subjects with Type 2 diabetes and coronary heart disease (CHD) with non-diabetic control subjects and to examine the relationship of plasma leptin to other CHD risk factors.. Serum leptin concentrations were measured in 144 Saudi men. Subjects studied included 59 with Type 2 diabetes mellitus [BMI 27.5 (3.7) kg/m2 mean (sd)], 34 with coronary heart disease [BMI 29.6 (1.8) kg/m2], and 51 non-diabetic controls [BMI 28.0 (3.5) kg/m2]. There was no significant difference in BMI between the groups. Fasting serum leptin, lipids, insulin, apolipoproteins and glucose were measured. BMI, blood pressure; smoking habit and age were also recorded. Insulin resistance was assessed using the HOMA model.. Leptin concentrations were significantly higher in diabetic and CHD patients than in controls (P = 0.024 and 0.016, respectively). Multiple regression analysis showed that body weight (P < 0.0006), serum triglyceride concentration (P = 0.046) and systolic blood pressure (P = 0.013) were all significantly related to the logarithm of the serum leptin concentration (R2 = 0.549) in CHD patients. A subgroup analysis, comparing those patients who had the metabolic syndrome, as defined by WHO, with controls, showed higher serum leptin in those with metabolic syndrome (P = 0.05).. Serum leptin is increased in Saudi subjects with diabetes mellitus, metabolic syndrome and CHD. Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance. Further studies are needed to evaluate this relationship prospectively.

Topics: Adult; Apolipoprotein A-I; Blood Glucose; Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Diastole; Humans; Insulin; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Saudi Arabia; Triglycerides

Topics: Animals; C-Reactive Protein; Coronary Disease; Diabetes Mellitus; Glucose Intolerance; Humans; Hypertension; Inflammation; Leptin; Lipoproteins, HDL; Matrix Metalloproteinase 9; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; Oxidative Stress; Phosphatidylcholine-Sterol O-Acyltransferase; Receptors, LDL; Risk Factors; Smoking

Leptin may correlate with insulin resistance and be an important factor in patients with coronary artery disease. Therefore, we examined whether plasma leptin levels and insulin resistance are linked with coronary artery disease.. Plasma leptin levels and insulin resistance, assessed by the hyperinsulinemic euglycemic clamp technique, were measured in control subjects (n = 12, mean age 62 +/- 10 years), and in patients with obstructive coronary artery disease (n = 15, mean age 64 +/- 8 years) or vasospastic angina (n = 12, mean age 62 +/- 12 years).. Plasma leptin levels were significantly higher (p < 0.017) in patients with obstructive coronary artery disease (8.4 +/- 2.7 ng/ml) and vasospastic angina (7.9 +/- 2.1 ng/ml) than in patients without obstructive coronary artery disease (4.7 +/- 1.4 ng/ml). Mean glucose infusion rate was significantly (p < 0.017) lower in patients with obstructive coronary artery disease (4.39 +/- 1.78 mg/kg/min) and vasospastic angina (3.57 +/- 1.72 mg/kg/min) than in patients without obstructive coronary artery disease (8.74 +/- 1.05 mg/kg/min). The plasma levels of leptin were negatively correlated with mean glucose infusion rate (r = -0.67, p < 0.01). The other coronary risk factors were similar in these three groups.. Plasma leptin levels are correlated with insulin resistance and may be associated with coronary artery disease.

Topics: Aged; Angina Pectoris, Variant; Coronary Disease; Female; Glucose Clamp Technique; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors

Topics: Biomarkers; Body Mass Index; Clinical Trials as Topic; Coronary Disease; Electrocardiography; Humans; Leptin; Obesity, Morbid; Predictive Value of Tests; Risk Factors; Scotland; Weight Loss

Obesity is a risk factor for many chronic diseases, including glucose intolerance, lipid disorders, hypertension, and coronary heart disease. Even though the body-mass index (BMI) is a heterogeneous phenotype reflecting the amount of fat, lean mass, and body build, several studies have provided evidence of one or two major loci contributing to the variation in this complex trait. We sought to identify loci with potential influence on BMI in the data obtained from National Heart, Lung, and Blood Institute Family Heart Study. Two complementary samples were studied: (a) 1,184 subjects in 317 sibships, with 243 markers typed by the Utah Molecular Genetics Laboratory (UMGL) and (b) 3,027 subjects distributed among 401 three-generation families, with 404 markers typed by the Mammalian Genotyping Service (MGS). A genome scan using a variance-components-based linkage approach was performed for each sample, as well as for the combined sample, in which the markers from each analysis were placed on a common genetic map. There was strong evidence for linkage on chromosome 7q32.3 in each sample: the maximum multipoint LOD scores were 4.7 (P<10-5) at marker GATA43C11 and 3.2 (P=.00007) at marker D7S1804, for the MGS and UMGL samples, respectively. The linkage result is replicated by the consistent evidence from these two complementary subsets. Furthermore, the evidence for linkage was maintained in the combined sample, with a LOD score of 4.9 (P<10-5) for both markers, which map to the same location. This signal is very near the published location for the leptin gene, which is the most prominent candidate gene in this region. For the combined-sample analysis, evidence of linkage was also found on chromosome 13q14, with D13S257 (LOD score 3.2, P=.00006), and other, weaker signals (LOD scores 1.5-1.9) were found on chromosomes 1, 2, 3, 5, 6, 14, and 15.

Topics: Body Mass Index; Chromosome Mapping; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 7; Coronary Disease; Genotype; Humans; Leptin; Lod Score; National Institutes of Health (U.S.); Obesity; Quantitative Trait, Heritable; United States

We studied 31 nondiabetic, habitually (> or =5 years) morbidly obese subjects (mean +/- SD body mass index [BMI] 43 +/- 8.7, median 43). Our specific aim was to determine whether metformin (2.55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD). The patients were instructed to continue their prestudy dietary and exercise regimens without change. After 2 baseline visits 1 week apart, the 27 women and 4 men began receiving metformin, 2.55 g/d, which was continued for 28 weeks with follow-up visits at study weeks 5, 13, 21, and 29. Daily food intake was recorded by patients for 7 days before visits then reviewed with a dietitian. Kilocalories per day and per week were calculated. At each visit, fasting blood was obtained for measurement of lipid profile, insulin, leptin, and PAI-Fx. The mean +/- SD kilocalories consumed per day, 1,951 +/- 661 at entry, fell by week 29 to 1,719 +/- 493 (P =.014) but did not differ at weeks 5, 13, and 21 from that at week 29 (P >.2). Weight fell from 258 +/- 62 pounds at entry to 245 +/- 54 pounds at week 29 (P =.0001). Girth was reduced from 51.8 +/- 6.2 to 49.2 +/- 4.5 inches (P =.0001). Waist circumference fell from 44.0 +/- 6.4 inches to 41.3 +/- 5.9 (P =.0001). The waist/hip ratio fell from 0.85 +/- 0.09 to 0.84 +/- 0.09 (P =.04). Fasting serum insulin, 28 +/- 15 microU/mL at entry, fell to 21 +/- 11 microU/mL at week 29 (P =.0001), and leptin fell from 79 +/- 33 ng/mL to 55 +/- 27 ng/mL (P =.0001). On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P <.007). Low-density lipoprotein (LDL) cholesterol, 126 +/- 34 mg/dL at study entry, fell to 112 +/- 43 mg/dL at week 29 (P =.001), with a linear trend toward decreasing levels throughout (P =.036). By stepwise linear regression, the higher the entry weight, the larger the reduction in weight on metformin therapy (partial R(2) = 31%, P =.001). The greater the reduction in kilocalories consumed per day, the greater the decrease in weight on metformin therapy (partial R(2) = 15%, P =.011). The higher the waist/hip ratio at entry, the greater its reduction on metformin therapy (partial R(2) = 11%, P =.004). The higher the entry serum leptin, the greater its reduction on metformin t

Topics: Adult; Aged; Body Mass Index; Body Weight; Cholesterol, LDL; Coronary Disease; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Metformin; Middle Aged; Obesity; Risk Factors; Tissue Plasminogen Activator

Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity. Therefore, we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS). Methods and Results- Plasma leptin levels were measured at baseline in 377 men (cases) who subsequently experienced a coronary event and in 783 men (controls) who remained free of an event during the 5-year follow-up period of the study. Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort. Leptin levels were significantly higher in cases than controls (5.87+/-2.04 ng/mL versus 5.04+/-2.09 ng/mL, P<0.001). In univariate analysis, for each 1 SD increase in leptin, the relative risk (RR) of an event increased by 1.25 (95% confidence interval [CI], 1.10 to 1.43; P<0.001). There was minimal change in this RR with correction for body mass index (RR, 1.24; 95% CI, 1.06 to 1.45; P=0.006) or with further correction for classic risk factors, including age, lipids, and systolic blood pressure (RR, 1.20; 95% CI, 1.02 to 1.42; P=0.03). Leptin correlated with C-reactive protein (r=0.24, P<0.001) and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein.. We show, for the first time, in a large prospective study that leptin is a novel, independent risk factor for coronary heart disease.

Topics: Age Factors; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Coronary Disease; Follow-Up Studies; Humans; Leptin; Lipids; Middle Aged; Multivariate Analysis; Risk Factors; Smoking; Triglycerides

Serum leptin is associated with the occurrence of cardiovascular risk factors but it is unknown whether leptin is also associated with cardiovascular disease. Another open question is whether the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is a determinant of circulating leptin.. We measured serum leptin concentrations in a large group of patients with angiographically assessed coronary artery disease (CAD) and investigated the relationship between the Trp64Arg polymorphism of the beta3-adrenergic receptor (AR) and serum leptin.. Leptin was measured in the fasting state in 1000 consecutive patients with angiographically confirmed CAD by radioimmunoassay. The codon 64 T/C polymorphism of the beta3-AR gene was analysed by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) technique. Controls were 1000 age-, gender- and weight-matched subjects without clinical signs of CAD.. Serum leptin concentrations were significantly higher in patients with CAD than in those without CAD (median: 6.8 vs 6.1 ng/ml, P < 0.001). In a multiple regression analysis leptin was found to be a determinant of CAD (P = 0.005) along with established risk factors. No differences in serum leptin were observed between wild-type and heterozygous carriers of the Trp64Arg mutation of the beta3-AR gene, whereas the small group of homozygous carriers had higher leptin due to their higher BMI. In a multiple linear regression analysis, body mass index, gender and fasting insulin were the main significant determinants of serum leptin, whereas the beta3-AR polymorphism had no effect.. Patients with coronary artery disease exhibit higher serum leptin concentrations than age- and gender-matched controls of comparable BMI, indicating that leptin could contribute to the development of cardiovascular disease, possibly via activation of the sympathetic nervous system. The Trp64Arg variant of the beta3-adrenoceptor did not influence serum leptin.

Topics: Aged; Arginine; Body Mass Index; Coronary Disease; Female; Genotype; Humans; Insulin; Leptin; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-3; Receptors, Leptin; Regression Analysis; Tryptophan

Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Proteins; Triglycerides

Topics: Adult; Coronary Disease; Cytokines; Diabetes Mellitus; Female; Humans; India; Interleukin-6; Leptin; Male; Proteins; Risk Factors; Rural Population; Social Class; Tumor Necrosis Factor-alpha; Urban Population

The human response to surgical stress is characterized by massive release of neuroendocrine hormones, provoking catabolism, thermogenesis, and hyperglycemia. Considering the possible adverse outcomes of excessive stress hormones, understanding various components of the stress response may improve management of postoperative morbidity. Leptin, initially described as an adipocyte-derived signaling factor, may also play an important role in regulating the hypothalamo-pituitary-adrenocortical axis. In phase I, plasma leptin and cortisol were measured in women before, during, and after total abdominal hysterectomy. The anesthetic technique was strictly controlled, balanced anesthesia. In phase II, plasma leptin and cortisol levels were measured in cardiac surgery patients. These subjects were anesthetized with a high dose opioid technique that blunts the intraoperative surgical stress response. In phase I, mean leptin levels did not change over the week before surgery, had a maximal decrease to 49% of baseline 2 h after surgery, and increased to just above baseline 24 h postoperatively. Cortisol was 176% of the baseline just before surgery, peaked at 2 h after surgery (383%), and remained elevated 24 h (200%) and 48 h (165%) after surgery. During the first 2 h of surgery, the decrease in leptin parallels the increase in cortisol. In phase II, high dose fentanyl limited both the cortisol increase and the leptin decrease; thus, the ratio of cortisol increase to leptin decrease was similar for the cardiac patients and the hysterectomy patients. These data indicate that leptin has a role in the surgically induced acute stress response in humans. Early in surgery the decrease in leptin parallels the increase in cortisol. This suggests a possible relationship between the neurobiology of these two systems, which could have important implications for regulation of the neuroendocrine response to surgical stress.

Topics: Adult; Aged; Analgesics, Opioid; Anesthesia; Cohort Studies; Coronary Artery Bypass; Coronary Disease; Female; Fentanyl; Humans; Hydrocortisone; Hysterectomy; Kinetics; Leptin; Middle Aged; Proteins; Stress, Physiological

To study the relationship between hyperinsulinaemia, insulin resistance, leptin and atherosclerosis in subjects with familial hypercholesterolaemia (FH).. Case-control cross-sectional study.. Lipid clinic, Johannesburg Hospital, South Africa.. Fasting serum lipid, glucose, insulin and leptin levels were measured in 24 homozygous FH subjects; 20 FH heterozygotes without coronary artery disease (CAD); 22 heterozygotes with documented CAD; and 20 healthy normocholesterolaemic subjects. Insulin resistance was calculated using the homeostasis model assessment (HOMA) formula.. Mean glucose and insulin levels were similar in all 4 groups. There was no significant difference in calculated insulin resistance between any of the groups. There was also no relationship between the degree of insulin resistance and total or LDL-cholesterol levels. Using Spearman's correlation coefficient (Rs) calculated insulin resistance correlated with triglyceride (Rs = 0.27; P<0.05) and inversely with HDL-cholesterol (Rs = -0.26; P<0.05). Fasting insulin concentrations and calculated insulin resistance were similar in FH subjects with overt CAD compared to those without. Leptin levels were higher in the FH subjects with CAD. However, these subjects were older and had a larger body mass index (BMI), and when adjusted for age and BMI, only BMI correlated with leptin levels (multiple r = 0.65; P<0.001).. In the absence of other causes of insulin resistance, FH subjects have normal fasting insulin levels and, in general, they are not insulin resistant. Insulin resistance appears to play little role in the pathogenesis of accelerated atherosclerosis in FH.

Topics: Adolescent; Adult; Arteriosclerosis; Blood Glucose; Body Mass Index; Coronary Disease; Female; Heterozygote; Homozygote; Humans; Hyperinsulinism; Hyperlipoproteinemia Type II; Insulin; Insulin Resistance; Leptin; Lipids; Male; Proteins

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

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