Available data suggest that hemoglobin A1c (A1c), also known as glycosylated hemoglobin, levels may be related to cardiovascular risk in the general population without diabetes mellitus. We sought to test this hypothesis prospectively in a cohort of women without overt cardiovascular disease.
We conducted a nested case-control study of the Women's Health Study cohort. We identified 464 case patients with incident myocardial infarction, stroke, or coronary revascularization and 928 unmatched control subjects who remained free of cardiovascular events at case diagnosis. The mean follow-up was 7 years.
Of the overall study population, 136 had a history of diabetes mellitus or an overtly elevated baseline A1c level (>6.4%) and were excluded from the primary analyses. Among women without diabetes mellitus or an elevated baseline A1c level, mean ± SD baseline levels of A1c were significantly higher among future cases than controls (5.47% ± 0.27% vs 5.37% ± 0.22%; P<.001). The crude relative risks (RRs) of incident cardiovascular events for increasing quartiles of A1c were 1.00, 0.98, 1.33, and 2.25 (95% confidence interval [CI] for the highest vs the lowest quartile, 1.59-3.18). The A1c levels correlated with several other traditional cardiovascular risk factors, and in fully adjusted models, the predictive effect of A1c was attenuated and not significant (RR for the highest vs the lowest quartile, 1.00; 95% CI, 0.65-1.54). In contrast, in the population including women with diabetes mellitus at enrollment, diabetes mellitus (RR, 4.97; 95% CI, 2.81-8.77) remained a strong independent determinant of cardiovascular risk in fully adjusted analyses, while A1c levels did not (RR for the highest vs the lowest quartile, 1.11; 95% CI, 0.73-1.71).
The A1c level is associated with future cardiovascular risk among women without diabetes mellitus, but this relationship is largely attributable to a strong correlation with other cardiovascular risk factors. In contrast, diabetes mellitus is a strong independent determinant of cardiovascular risk, even after adjustment for A1c levels.