Hemoglobin A _1c 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 ( N urses' H ealth S tudy) and men ( H ealth P rofessionals F ollow‐up S tudy). 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.