Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke The Framingham Study

Background and Purpose-Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. Methods-We measured serum IGF-1 levels in 757 elderly individuals (mean age 79 +/- 5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. Results-During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P=0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke (P<0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P=0.007) and 41% (hazardratio, 0.59; 95% confidence interval, 0.37-0.95; P=0.031) lower risk of incident ischemic stroke, respectively. Conclusions-IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.