Insulin resistance and risk of ischemic stroke among nondiabetic individuals from the northern Manhattan study

Background: Whether insulin resistance predicts ischemic stroke (IS) is still a matter of debate. Objective: To determine the association between insulin resistance (IR) and risk of first ischemic stroke in a large, multiethnic, stroke-free cohort without diabetes. Design: Prospective, population-based cohort study. Setting: Longitudinal epidemiologic study. Participants: A cohort of 1509 nondiabetic participants from the Northern Manhattan Study (mean [SD] age, 11 [10] years; 64.2% women; 58.9% Hispanics). Main Outcome Measures: Insulin sensitivity, expressed by the homeostasis model assessment (HOMA) of insulin sensitivity (HOMA index = [fasting insulin X fasting glucose]/22.5). Insulin resistance was defined by a HOMA-IR index in the top quartile (Q4). Cox proportional hazards models were used to determine the effect of HOMA-IR on the risk of incident IS, myocardial infarction (MI), vascular death, and combined outcomes (IS, MI, and vascular death). Results: The mean (SD) HOMA-IR was 2.3 (2.1), and Q4 was at least 2.8. During mean follow-up of 8.5 years, vascular events occurred in 180 participants; 46 had fatal or nonfatal IS, 45 had fatal or nonfatal MI, and 121 died of vascular causes. The HOMA-IR Q4 vs less than Q4 significantly predicted the risk of IS only (adjusted hazard ratio, 2.83; 95% confidence interval, 1.34-5.99) but not other vascular events. This effect was independent of sex, race/ethnicity, traditional vascular risk factors, and metabolic syndrome and its components. Conclusions: Insulin resistance estimated using the HOMA is a marker of increased risk of incident stroke in nondiabetic individuals. These findings emphasize the need to better characterize individuals at increased risk for IS and the potential role of primary preventive therapies targeted at IR.