Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: In apparently healthy men, circulating total adiponectin, adipsin, resistin, leptin and PAI-1 were not independent predictors of future CHD event. International Journal of Obesity (2010) 34, 118-126; doi:10.1038/ijo.2009.204; published online 13 October 2009