Leptin and adiponectin independently predict a first-ever myocardial infarction with a sex difference

Abstract Introduction The adipose tissue is an active endocrine organ which secretes numerous substances (adipokines) of importance for metabolism and the cardiovascular system. In obesity, circulating levels of several adipokines are altered which has been associated with the development of cardiovascular disease (CVD). Amongst them, leptin and adiponectin have been associated with atherosclerosis. Stipulated mechanisms for the adverse effects of high leptin levels and low adiponectin levels associated with obesity may be elevated blood pressure, endothelial dysfunction, glucose intolerance, to mention a few. Purpose To examine if leptin and adiponectin independently predict the development of myocardial infarction (MI). Methods In this prospective nested case-referent study, two cohorts of patients with a first-ever MI were identified (discovery n=564, validation n=1134) that had before the MI participated in a large population-based cohort study. Two referents were matched to every case, and leptin and adiponectin were measured from stored baseline survey plasma samples. Uni- and multivariable conditional logistic regression was used to estimate the risk for future MI. Results In the discovery cohort, 30.9% were women and the median age (IQR) at survey was 59.0 (10.1) years, and 60.6 (11.2) years at the MI. In the validation cohort, 26.3% were women and the median age at survey was 58.3 (10.2) years and 63.7 (11.8) years at the MI. In the univariable logistic regression model, elevated leptin, a high L/A-ratio and low adiponectin associated with future MI, also after stratification for sex. In the multivariable analysis adjusting for BMI, high leptin levels and a high leptin/adiponectin-ratio were associated with a higher risk for MI (OR 95% CI); 1.26 (1.10–1.45) and 1.36 (1.19–1.55) respectively. High levels of adiponectin were associated with a reduced risk of future MI 0.81 (0.73–0.91). Following stratification, the association remained only in men. The results were largely replicated in the validation cohort. Conclusion High leptin and low adiponectin predict first-ever MI, notably with a sex difference. These findings may increase our understanding of obesity-related CVD.