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

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.