Abstract
Background: Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is some inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of first ever stroke in an elderly community-based population. Methods: Serum leptin levels were assayed in 757 stroke-free individuals (mean age 79 [SD, 5 years], 62% women) from the Framingham Original cohort at the 22nd examination cycle (1990-1994). Incidence of all-stroke and ischemic stroke were prospectively ascertained. Results: During a mean follow-up of 10 years, 119 individuals developed stroke, 99 of whom had ischemic stroke. In multivariable Cox regression models, log-leptin levels were not associated with incidence of all-stroke or ischemic stroke (hazard ratios [HR] per SD increment in log-leptin 0.9 [0.73-1.09] and 0.89 [0.72-1.11], respectively). The results were highly suggestive for effect modification by WHR for the association between leptin and ischemic stroke. Analysis in sub-groups stratified by waist-to-hip ratio (WHR) and adjusting for age, sex and established stroke risk factors revealed a lower incidence of first-ever all-stroke and ischemic stroke associated with higher leptin levels among subjects in the top WHR quartile but not in others (HR, 0.64 [0.43, 0.95] versus 0.98 [0.77, 1.25] for incident all-stroke and 0.61 [0.39, 0.95] versus 0.96 [0.74, 1.26] for ischemic stroke). Conclusions: Our data suggests that leptin may exert protective effects against first ever stroke in obese individuals. Further investigations are required to confirm these findings and explore possible mechanisms for this protective effect.
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