leptin and Acute-Coronary-Syndrome

Leptin, a well-proven cardiovascular risk factor, influences vascular endothelial growth factor A (VEGF A) synthesis via hypoxia-inducible factor 1 alpha (HIF-1A), nuclear factor kappa-light-chain-enhancer of activated B cells (NfkB) and NILCO (Notch, interleukin 1 [IL1] and leptin cross-talk outcome) pathways. This study aimed to investigate the influence of cardiac rehabilitation (CR) on HIF-1A, NfkB and NILCO dependent leptin and VEGF A cross-talk in patients after acute coronary syndrome (ACS). Fifty post-ACS patients underwent a 2-week CR programme (study group S) and were compared to 50 post-ACS subjects who did not undergo CR (control group K). In group S, at baseline and at completion and in group K once, anthropometric, body composition, blood pressure and heart rate measurements were taken and blood sampling was performed. Serum levels of leptin, VEGF A, VEGF receptor 2 (VEGF R2), HIF-1A, NfkB, interleukin 1-alpha (IL1-alpha) and Notch 1 were determined. In group S, serum VEGF A levels increased while leptin, HIF-1A and VEGF R2 levels decreased and completion but not baseline serum leptin correlated positively with serum VEGF A. Also, serum completion VEGF A correlated positively with NfkB and HIF-1A in group S. Correlation analysis in group S confirmed the significant role of the NILCO pathway in the regulation of VEGF A serum levels mediated by HIF-1A and NfkB. CR may induce the predomination of the NILCO pathway interacting with HIF-1A and NfkB over leptin canonical and non-canonical signalling pathways in the leptin influence on VEGF A in post-ACS patients.Trial registration: ClinicalTrials.gov ID: NCT03935438. The CARDIO-REH randomised study.

Topics: Acute Coronary Syndrome; Cardiac Rehabilitation; Humans; Interleukin-1; Leptin; NF-kappa B; Vascular Endothelial Growth Factor A

Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients.. Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke.. In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031).. High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

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

Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome.

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Biomarkers; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Heptanoic Acids; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infections; Leptin; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Pravastatin; Pyrroles; Recurrence; Resistin; Retrospective Studies; Risk Factors; Survival Rate; Thrombolytic Therapy; United States

As endocrine organ, adipose tissue may modulate inflammatory response by releasing a wide range of mediators, known as adipocytokines. Due to the complex balance between pro- and anti-inflammatory activity their pathophysiological and prognostic role in cardiovascular (CV) diseases still remains debated. Here, we consider the potential associations of circulating adipocytokines adiponectin, leptin and their ratio (LAR), with metabolic and inflammatory profiles in 217 patients with severe carotid stenosis. A prospective analysis investigating their predictive role toward acute coronary syndromes (ACS) was also drawn over a 12-month follow-up period. Serum leptin was positively associated with fasting insulinemia and HOMA-IR, but not with lipid profile and inflammation. Conversely, adiponectin was negatively associated with glucose, insulin, HOMA-IR, triglycerides and both systemic and intraplaque inflammatory markers whereas a positive association with high-density lipoprotein cholesterol (HDL-c) was observed. Accordingly, a significant association with metabolic profile was reported for LAR. According to the cut-off point identified by ROC curve, adiponectin values≤2.56μg/mL were correlated with a higher risk of ACS occurrence at 12months' follow-up (p-value for Log Rank test=0.0003). At Cox regression analysis the predictive ability of low serum adiponectin was confirmed also after adjustment for age, male gender and diabetes. In conclusion, adiponectin may be considered a biomarker of metabolic compensation, inversely associated with chronic low-grade inflammation. Circulating adiponectin is also associated with lower risk of adverse CV events in patients with severe carotid stenosis.

Topics: Acute Coronary Syndrome; Adiponectin; Aged; Area Under Curve; Biomarkers; Blood Glucose; Carotid Stenosis; Down-Regulation; Female; Humans; Inflammation Mediators; Insulin; Kaplan-Meier Estimate; Leptin; Lipids; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; ROC Curve; Severity of Illness Index; Time Factors

We attempted to investigate the potential association between leptin and coronary collateral vessel development in patients with non-ST elevation acute coronary syndromes (NSTE-ACS).. One hundred and nineteen consecutive patients with NSTE-ACS with high-grade coronary stenosis or occlusion in at least one epicardial coronary artery were prospectively enrolled in a cross-sectional observational study. Serum leptin levels measured in all patients. Collateral circulation was graded according to the Rentrop classification. Firstly, we divided patients into two groups as good and poor collateral group. Patients with Rentrop 2.3 were regarded as good collateral group. Patients in Rentrop grades 0, 1 classified as poor collateral group. Secondly, patients were divided into collateral (+) group and collateral (-) group. Collateral (+) group included the patients with grade 1, 2, 3 collateral development. Collateral (-) group was composed of the patients with Rentrop 0. Statistical analysis was performed using Student t-test, Mann-Whitney U test, Chi-square test, Kruskal -Wallis test and Spearman's correlation.. We did not find statistically significant difference between good and poor collateral groups with regard to leptin levels [4.2 (1.8-8.6) ng/mL and 6.4 (2.4-12.6) ng/mL, p=0.22, respectively]. There was no statistically significant difference in leptin levels between collateral (+) group and collateral (-) groups [4.7 (1.7-10.5) ng/mL and 6.8 (2.7-12.1) ng/mL, p=0.33, respectively]. We observed that there was lower leptin level at higher Rentrop grades [Rentrop 0; 6.8 (2.5-12.5) ng/mL, Rentrop 1; 5.9 (1.7-14.1) ng/mL, Rentrop 2; 4.3 (1.7-8.7) ng/mL, Rentrop 3; 3.9 (2.1-9.7) ng/mL]. However, this difference did not reach statistically significant level (p=0.54). In addition, we did not find statistically significant correlation between Rentrop grades and leptin levels (p=0.246, r=-0.107).. The present study reveals no association between serum leptin level and coronary collateral development.. AMAÇ: ST yükselmesi olmayan akut koroner sendromlu (NSTE-AKS) hastalarda serum leptin düzeyi ile koroner kollateral gelişimi arasındaki potansiyel ilişkiyi incelemeyi hedefledik. YÖNTEMLER: Bu kesitsel ve gözlemsel çalışmaya en az bir epikardiyal koroner arterinde ciddi darlık veya total oklüzyon olan 119 NSTE-AKS hastası alındı. Tüm hastalarda serum leptin düzeyleri ölçüldü. Kollateral gelişimi Rentrop klasifikasyonuna göre değerlendirildi. İlk olarak hastalar iyi ve kötü kollateral grup olarak ikiye ayrıldı. Rentrop 2 ve 3 hastalar iyi kollateral grup, Rentrop 0 ve 1 hastalar kötü kollateral grup olarak adlandırıldı. Daha sonra hastalar kollateral (+) grup ve kollateral (-) grup olarak sınıflandırıldı. Kollateral (+) grup Rentrop 1,2,3 hastalardan, kollateral (-) grup Rentrop 0 hastalardan oluştu. İstatistiksel analiz olarak Student t-testi, Mann-Whitney U testi, Ki-kare testi, Kruskal Wallis testi ve Spearman korelasyon analizleri kullanıldı.. Serum leptin düzeyleri bakımından iyi ve kötü kollateral grup arasında istatistiki anlamlı bir fark bulmadık [sırasıyla, 4.2 (1,8-8,6) ng/mL and 6,4 (2,4-12,6) ng/mL, p=0,22]. Kollateral (+) ve kollateral (-) grup arasında da leptin düzeyleri arasında istatistiki fark yoktu [sırasıyla, 4,7 (1,7-10,5) ng/mL and 6.8 (2,7-12,1) ng/mL, p=0,33]. Tüm Rentrop dereceleri ayrı ayrı değerlendirildiğinde, yüksek Rentrop derecelerinde düşük leptin düzeyleri saptadık [Rentrop 0; 6,8 (2,5-12,5) ng/mL, Rentrop 1; 5,9 (1,7-14,1) ng/mL, Rentrop 2; 4,3 (1,7-8,7) ng/mL, Rentrop 3; 3,9 (2,1-9,7) ng/mL]. Fakat bu fark da istatistiki anlamlılığa ulaşmadı (p=0,54). Bunların yanı sıra Rentrop dereceleri ile leptin düzeyleri arasında korelasyon olup olmadığı araştırıldı ve aralarında istatistiki anlamlı bir korelasyon saptanmadı (p=0,246, r=-0,107). SONUÇ: Bu çalışmada serum leptin düzeyi ile koroner kollateral gelişimi arasında bir ilişki saptanmadı.

Topics: Acute Coronary Syndrome; Biomarkers; Collateral Circulation; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Severity of Illness Index

A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques.. The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability.. Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability.. Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Topics: Acute Coronary Syndrome; Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Vessels; Disease Progression; Electrocardiography; Female; Humans; India; Inflammation Mediators; Leptin; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Plaque, Atherosclerotic; Predictive Value of Tests; Pregnancy-Associated Plasma Protein-A; Risk Assessment; Risk Factors; Rupture, Spontaneous

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Topics: Acute Coronary Syndrome; Atherosclerosis; Cell Adhesion Molecules; Cells, Cultured; Coronary Thrombosis; Coronary Vessels; Endothelial Cells; Enzyme Inhibitors; Humans; Leptin; NF-kappa B; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Reactive Oxygen Species; Thromboplastin

Leptin, a recently discovered obesity gene product, is primarily involved in the regulation of food intake and energy expenditure. Recent observations suggest that leptin has a much broader biological role other than regulation of body weight and energy metabolism. It has been shown that leptin increases sympathetic nerve activity, stimulates generation of reactive oxygen species, induces platelet aggregation and promotes arterial thrombosis, and is an independent risk factor for coronary heart disease. In this paper, we discussed the role of leptin in the pathogenesis of acute coronary syndromes and its usefulness as a biomarker for risk stratification in acute coronary syndromes.

Topics: Acute Coronary Syndrome; Biomarkers; Humans; Leptin; Obesity; Risk Factors; Time Factors

By activating immune cells or a direct action on the vascular wall, leptin may affect the initiation and progression of atherosclerosis. We investigated whether plasma leptin concentration is associated with coronary artery disease, with particular focus on the relationship between plasma leptin and the development of an acute coronary syndrome. Plasma leptin, interleukin-6 and high-sensitivity C-reactive protein were measured in 34 patients with acute coronary syndrome and 21 with stable angina. Their results were compared with those of 21 normal controls. Plasma leptin levels were significantly higher in the acute coronary syndrome group (13.36 +/- 5.02 ng.mL(-1)) compared to the stable angina group (8.97 +/- 4.06 ng.mL(-1)) or normal controls (5.14 +/- 2.75 ng.mL(-1)). Interleukin-6 and high-sensitivity C-reactive protein were also higher in the acute coronary syndrome group, and leptin correlated positively with interleukin-6 and high-sensitivity C-reactive protein. These findings suggest that plasma leptin levels may be a useful marker of systemic inflammation, and measurement of plasma leptin may be helpful in assessing the risk of developing coronary heart disease.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Stenosis; Female; Humans; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Risk Assessment; Up-Regulation