Glycemic control and coronary heart disease risk in persons with and without diabetes: The atherosclerosis risk in communities study

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.