Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study

Ann Intern Med. 2000 Jul 18;133(2):81-91. doi: 10.7326/0003-4819-133-2-200007180-00007.


Background: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease.

Objective: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes.

Design: Prospective cohort study.

Setting: The Atherosclerosis Risk in Communities (ARIC) Study.

Participants: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease.

Measurements: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995.

Results: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat.

Conclusions: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoproteins / blood
  • Body Constitution
  • Cholesterol, HDL / blood
  • Coronary Disease / epidemiology
  • Coronary Disease / etiology*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Factor VIII / metabolism
  • Female
  • Fibrinogen / metabolism
  • Follow-Up Studies
  • Humans
  • Incidence
  • Leukocyte Count
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Serum Albumin / metabolism
  • von Willebrand Factor / metabolism


  • Apolipoproteins
  • Cholesterol, HDL
  • Serum Albumin
  • von Willebrand Factor
  • Factor VIII
  • Fibrinogen