Hamidreza Saber1, Jayandra J Himali1, Alexa S Beiser1, Ashkan Shoamanesh1, Aleksandra Pikula1, Ronenn Roubenoff1, Jose R Romero1, Carlos S Kase1, Ramachandran S Vasan1, Sudha Seshadri2. 1. From the Framingham Heart Study, MA (H.S., J.J.H., A.S.B., J.R.R., C.S.K., R.S.V., S.S.); Boston University School of Public Health, MA (J.J.H., A.S.B.); McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada (A.S.); Department of Neurology, University of Toronto, Ontario, Canada (A.P.); Department of Medicine, Tufts University School of Medicine, Boston, MA (R.R.); Department of Neurology, Boston University School of Medicine, MA (J.J.H., A.S.B., J.R.R., C.S.K., R.S.V., S.S.); and Department of Neurology, Wayne State University School of Medicine, Detroit, MI (H.S.). 2. From the Framingham Heart Study, MA (H.S., J.J.H., A.S.B., J.R.R., C.S.K., R.S.V., S.S.); Boston University School of Public Health, MA (J.J.H., A.S.B.); McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada (A.S.); Department of Neurology, University of Toronto, Ontario, Canada (A.P.); Department of Medicine, Tufts University School of Medicine, Boston, MA (R.R.); Department of Neurology, Boston University School of Medicine, MA (J.J.H., A.S.B., J.R.R., C.S.K., R.S.V., S.S.); and Department of Neurology, Wayne State University School of Medicine, Detroit, MI (H.S.). suseshad@bu.edu.
Abstract
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% (hazard ratio, 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.
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% (hazard ratio, 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.
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