Insulin Resistance, the Metabolic Syndrome, and Incident Cardiovascular Events in the Framingham Offspring Study

The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.’s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5–2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2–2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartile]: 0.5 [0.3–0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3–0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8–2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P ≤ 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.