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The Atherosclerosis Risk in Communities Study

Elizabeth Selvin, PhD, MPH; Josef Coresh, MD, PhD; Sherita H. Golden, MD, MHS; Frederick L. Brancati, MD, MHS; Aaron R. Folsom, MD; Michael W. Steffes, MD, PhD

Arch Intern Med. 2005;165:1910-1916.

Background  Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A_1c (HbA_1c) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain.

Methods  We conducted a prospective case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study. Using proportional hazards models, we assessed the relation between HbA_1c level and incident CHD during 8 to 10 years of follow-up.

Results  In adults with diabetes, the relative risk (RR) of CHD was 2.37 (95% confidence interval [CI], 1.50-3.72) for the highest quintile of HbA_1c level compared with the lowest after adjustment for CHD risk factors. In persons without diabetes, the adjusted RR of CHD in the highest quintile of HbA_1c level was 1.41 (95% CI, 0.90-2.30); however, there was evidence of a nonlinear relationship in this group. In nondiabetic adults, HbA_1c level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA_1c levels. In the adjusted model, the RR of CHD for a 1–percentage point increase in HbA_1c level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA_1c level greater than 4.6%. In diabetic adults, the RR was 1.14 (95% CI, 1.07-1.21) per 1–percentage point increase in HbA_1c across the full range of HbA_1c values.

Conclusion  Elevated HbA_1c level is an independent risk factor for CHD in persons with and without diabetes.

Author Affiliations: Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research (Drs Selvin, Coresh, Golden, and Brancati), Johns Hopkins Bloomberg School of Public Health, Baltimore, Md; Johns Hopkins School of Medicine, Baltimore (Drs Coresh, Golden, and Brancati); and Division of Epidemiology and Community Health, School of Public Health (Dr Folsom) and Department of Laboratory Medicine and Pathology, Medical School (Dr Steffes), University of Minnesota, Minneapolis.

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