Leptin and Coronary Heart Disease Prospective Study and Systematic Review

Objectives This study sought to better determine the link between leptin and coronary heart disease (CHD). Background Circulating leptin is considered a risk factor for CHD but larger studies are needed. Methods 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. Results 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). Conclusions Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI. (J Am Coll Cardiol 2009; 53: 167-75) (C) 2009 by the American College of Cardiology Foundation