Hemoglobin A1c Is Associated With Increased Risk of Incident Coronary Heart Disease Among Apparently Healthy, Nondiabetic Men and Women

Background-Hemoglobin A1c (HbA(1c)), a time-integrated marker of glycemic control, predicts risk of coronary heart disease (CHD) among diabetics. Few studies have examined HbA(1c) and risk of CHD among women and men without clinically elevated levels or previously diagnosed diabetes. Methods and Results-We conducted parallel nested case-control studies among women (Nurses' Health Study) and men (Health Professionals Follow-up Study). During 14 and 10 years of follow-up, 468 women and 454 men developed incident nonfatal myocardial infarction (MI) and fatal CHD. Controls were matched 2: 1 based on age, smoking, and date of blood draw. For these analyses, participants with a history of diabetes or HbA(1c) levels >= 6.5% at baseline were excluded. Compared with HbA(1c) of 5.0% to <5.5%, those with an HbA(1c) of 6.0% to <6.5% had a multivariable-adjusted relative risk (RR) of CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men. The pooled RR of CHD was 1.29 (95% CI 1.11 to 1.50) for every 0.5%-increment increase in HbA(1c) levels and 1.67 (95% CI 1.23 to 2.25) for every 1%-increment increase, with the risk plateauing around 5.0%. Furthermore, participants with HbA(1c) levels between 6.0% and <6.5% and C-reactive protein levels >3.0 mg/L had a 2.5-fold higher risk of CHD compared with participants in the lowest categories of both biomarkers. Conclusions-Our findings suggest that HbA(1c) is associated with CHD risk among apparently healthy, nondiabetic women and men and may be an important early clinical marker of disease risk.