Leptinemia Is Not a Risk Factor for Ischemic Heart Disease in Men: Prospective results from the Quebec Cardiovascular Study

OBJECTIVE: To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat. RESEARCH DESIGN AND METHODS: The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BMI, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic patients and those in whom leptin levels could not be measured, we were able to compare the initial metabolic profiles of 86 men in the IHD group and of 95 control subjects. RESULTS: Plasma leptin concentrations were positively correlated with BMI (r = 0.67, P < 0.0001) and with fasting insulin concentrations (r = 0.46, P < 0.0001) in the overall sample. These significant associations were also observed when men with IHD and the control subjects were examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin; IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of plasma triglyceride (r = 0.25, P < 0.001), no significant association was found between leptin and plasma lipoprotein and lipid concentrations. Furthermore, plasma insulin remained significantly associated with leptin levels even after adjustment for BMI (r = 0.22, P < 0.005). There was no difference in baseline leptin levels among men who developed IHD versus men who remained IHD-free during the 5-year follow-up (5.56 +/- 3.12 vs. 5.36 +/- 2.90 ng/ml, respectively). Thus, although significantly correlated with the BMI and fasting insulin levels, plasma leptin concentration was not a significant predictor of the 5-year incidence of IHD. This lack of a relationship to IHD was noted when leptin levels were analyzed as tertiles and when leptin concentration was analyzed as a continuous variable. CONCLUSIONS: These prospective results suggest that leptinemia, despite being a strong correlate of obesity, does not appear to be an independent risk factor for the development of IHD in men.