Obesity and risk of incident heart failure in older men with and without pre-existing coronary heart disease: does leptin have a role?

Objectives: We examined the relationship between body mass index (BMI), waist circumference, and incident HF in men with and without pre-existing coronary heart disease (CHD) and assessed the contribution of plasma leptin concentration to these associations.

Background: Leptin has been proposed as a potential link between obesity and heart failure (HF).

Methods: This was a prospective study of 4,080 men age 60 to 79 years with no diagnosed HF followed for a mean period of 9 years, in whom there were 228 incident HF cases.

Results: Increased BMI was associated with significantly increased risk of HF in men with and without pre-existing CHD (myocardial infarction or angina) after adjustment for cardiovascular risk factors including C-reactive protein. The adjusted hazard ratios (HRs) associated with a 1-SD increase in BMI were 1.37 (95% confidence interval [CI]: 1.09 to 1.72) and 1.18 (95% CI: 1.00 to 1.39) in men with and without CHD, respectively. Increased leptin was significantly associated with an increased risk of HF in men without pre-existing CHD, independent of BMI and potential mediators (adjusted HR for a 1-SD increase in log leptin: 1.30 [95% CI: 1.06 to 1.61]; p = 0.01). However, no association was seen in those with pre-existing CHD (corresponding HR: 1.06 [95% CI: 0.77 to 1.45]; p = 0.72). Adjustment for leptin abolished the association between BMI and HF in men with no CHD; in those with CHD, the association between BMI and HF remained significant (p = 0.03). Similar patterns were seen for waist circumference.

Conclusions: In the absence of established CHD, the association between obesity and HF may be mediated by plasma leptin. In those with CHD, obesity appears to increase the risk of HF independent of leptin.