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Nontraditional Risk Factors for Coronary Heart Disease Incidence among Persons with Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Isao Saito, MD, PhD; Aaron R. Folsom, MD; Frederick L. Brancati, MD; Bruce B. Duncan, MD, PhD; Lloyd E. Chambless, PhD; and Paul G. McGovern, PhD
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Copyright ©2004 by the American College of Physicians


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

Figures

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Figure 1.
Relative risks and 95% CIs for incident coronary heart disease by tertiles or quartiles of baseline risk factors among participants with diabetes in the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1995.

Each risk factor was examined separately in two multivariate models. Model 1 was adjusted for sex, age, ethnicity, and ARIC field center. Model 2 was adjusted for the factors in model 1 plus cigarette smoking; alcohol drinking; sport index score; body mass index; levels of total cholesterol, high-density lipoprotein ( ) cholesterol, and triglycerides; and hypertension. values represent tests for log-linear associations using continuous variables.

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Figure 2.
Relative risks and 95% CIs for incident coronary heart disease by quartiles of baseline hemostatic risk factors among participants with diabetes in the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1995.P

Each risk factor was examined separately in two multivariate models. Model 1 was adjusted for sex, age, ethnicity, and ARIC field center. Model 2 was adjusted for the factors in model 1 plus cigarette smoking; alcohol drinking; sport index score; body mass index; levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides; and hypertension. values represent tests for log-linear associations using continuous variables.

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Figure 3.
Relative risks and 95% CIs for incident coronary heart disease by tertiles or quartiles of selected baseline risk factors among participants with diabetes in the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1995.P

Each risk factor was examined separately. Relative risks are adjusted for treatment status for diabetes in addition to sex; age; ethnicity; ARIC field center; cigarette smoking; alcohol drinking; sport index score; body mass index; levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides; and hypertension. values represent tests for log-linear associations using continuous variables.

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