title: Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.
abstract: BACKGROUND
  The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated 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 neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, 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 associated 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) had 1.4-fold (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) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles.
  
  
  CONCLUSIONS
  Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.
authors.affiliation: Research Institute of Public Health, University of Kuopio, Finland. Hanna-Maaria.Lakka@uku.fi
authors.forename: H M
authors.initials: HM
authors.lastname: Lakka
authors.forename: T A
authors.initials: TA
authors.lastname: Lakka
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: J
authors.initials: J
authors.lastname: Sivenius
authors.forename: J T
authors.initials: JT
authors.lastname: Salonen
mesh_terms: D000208:Acute Disease; D000328:Adult; D002318:Cardiovascular Diseases / Q000401:mortality*; D002561:Cerebrovascular Disorders / Q000209:etiology*; D016001:Confidence Intervals; D003327:Coronary Disease / Q000209:etiology*; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors