BACKGROUND: Hemoglobin A1c (HbA1c) as a marker of long-term glycemic control is used for the diagnosis and assessment of treatment of diabetes mellitus. OBJECTIVES: The authors aimed to evaluate whether HbA1c levels would independently associate with long-term survival independent of the presence of other cardiovascular risk factors. METHODS: The present retrospective analysis is based on the longitudinal the Essen Coronary Artery Disease registry of consecutive patients undergoing coronary revascularization therapy between 2004 and 2019. Cox regression analysis was used to determine the association of HbA1c with all-cause mortality. To assess for nonlinearity between HbA1c as a continuous variable and all-cause mortality, we fitted restricted cubic spline models. Kaplan-Meier analysis was used to depict the survival probability. RESULTS: Overall, 4,700 patients (mean age 66.1 ± 11.4 years, 77.1% male) were included. Mean HbA1c was 6.3% ± 1.2%. During a median follow-up of 2.8 (IQR: 0.6-6.2) years, 558 patients (8.4%) died. In multivariable analysis, higher HbA1c levels, adjusted for other cardiovascular risk factors, were independently associated with all-cause mortality (HR: 1.16 [95% CI: 1.07-1.26] per 1 SD change in HbA1c, P <
0.001). Using HbA1c >
5.3% to 5.6% as reference, we observed a U-shaped event rate for different HbA1c groups (≤5.3%: HR: 1.52 [95% CI: 1.01-2.28], P = 0.0044
>
5.6%-5.9%: HR: 0.96 [95% CI: 0.65-1.41], P = 0.80
>
5.9%-6.6%: HR: 1.26 [95% CI: 0.90-1.78], P = 0.20
>
6.6-7.8: HR: 1.38 [95% CI: 0.93-2.04], P = 0.10
≥7.8%: HR: 2.15 [95% CI: 1.43-3.19], P <
0.001). CONCLUSIONS: In the present large registry of patients with established coronary artery disease (CAD) undergoing coronary revascularization therapy, HbA1c levels display a U-shaped association with all-cause mortality. In addition to patients with diabetes, also patients with CAD with very low HbA1c face increased mortality risk. Clinical trials, randomizing to different HbA1c targets are needed to define optimal HbA1c targets for patients with established CAD.