Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men - The Kuopio ischaemic heart disease risk factor study

Background: The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associ ated with increased cardiovascular morbidity and mortality. Methods: Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with nei ther cardiovascular disease nor diabetes at baseline. Forty-five cardiovasc ular deaths, 110 acute coronary events. 48 strokes, and 163 any cardiovascu lar events occurred during an average follow-up of 9.5 years. A total of 16 3 cardiovascular events (45 cardiovascular deaths, 110 acute coronary event s, and 48 strokes) occurred during an average follow-up of 9.5 years. Results: In Cox regression analysis adjusting for age and examination years , fasting serum insulin level as a continuous variable was directly associa ted with the risk of cardiovascular death (P = .006), acute coronary events (P = .04), and stroke (P = .02). Men with insulin levels of 52 to 66 pmol/ L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) bad 1.4-fol d (95%, confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0 .5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P = .05) cardiovas cular mortality, respectively, compared with men with insulin levels of les s than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment f or serum lipid levels, blood pressure, and obesity reduced the excess cardi ovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, re spectively. There were no statistically significant differences in the inci dence of acute coronary events and stroke between the insulin quartiles, Conclusions: Hyperinsulinemia had a modest association with increased cardi ovascular mortality in middle-aged men. This relationship was largely expla ined by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.