Abstract
Background: Insulin-like growth factor 1 (IGF-1), reduces progression of atherosclerosis and in cross-sectional studies low circulating IGF-1 is associated with increased carotid intima-media thickness. Yet, prospective data linking IGF-1 levels to development of stroke remain sparse and inconsistent. We related circulating IGF-1 levels to risk of incident stroke in a community-dwelling sample. Methods: Serum IGF-1 levels were assayed in 757 stroke-free participants (age 79+5 years, 62% women) from the Framingham original cohort (1990-1994), and related to prospectively ascertained, incident all-stroke and ischemic stroke using Cox models. Results: During a mean follow-up of 10.2 years in 757 participants, 119 developed stroke including 99 with ischemic stroke. After adjustment for age and sex, higher log-IGF1 levels were associated with a lower risk of incident ischemic stroke [hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.63- 0.99, p=0.043]. There was a threshold effect with subjects in the lowest quintile of IGF-1 levels having 2.56-fold higher risk of incident ischemic stroke (95% CI: 1.20, 5.45, p=0.015) compared to all others. We observed significant interaction between diabetes and IGF1 in their relation to ischemic stroke (p=0.016). In pre-specified subgroup analyses the effect was restricted to persons with diabetes and central obesity (waist-to-hip ratio in top quartile) in whom each SD increase in IGF-1 was associated with a 61% (HR: 0.39, 95%CI: 0.20-0.78, p=0.007), and 41% (HR: 0.59, 95%CI: 0.37- 0.95, p=0.031) lower risk of incident ischemic stroke, respectively. Results were similar for all-stroke. Conclusions: IGF-1 may have a protective role in the pathogenesis of ischemic stroke among persons with insulin resistance as manifested by diabetes and/or obesity.
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