Hemoglobin A1c level and future cardiovascular events among women.
BACKGROUND
Available data suggest that hemoglobin A(1c) (A(1c)), 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.


METHODS
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.


RESULTS
Of the overall study population, 136 had a history of diabetes mellitus or an overtly elevated baseline A(1c) level (>6.4%) and were excluded from the primary analyses. Among women without diabetes mellitus or an elevated baseline A(1c) level, mean +/- SD baseline levels of A(1c) 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 A(1c) 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 A(1c) levels correlated with several other traditional cardiovascular risk factors, and in fully adjusted models, the predictive effect of A(1c) 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 A(1c) levels did not (RR for the highest vs the lowest quartile, 1.11; 95% CI, 0.73-1.71).


CONCLUSIONS
The A(1c) 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 A(1c) levels.
Blake
Gavin J
GJ
Cardiovascular Division, the Center for Cardiovascular Disease Prevention, and the Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA. blake_gj@yahoo.com
Pradhan
Aruna D
AD
Manson
JoAnn E
JE
Williams
G Rhys
GR
Buring
Julie
J
Ridker
Paul M
PM
Glynn
Robert J
RJ
D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000209:etiology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000209:etiology
D006442:Glycated Hemoglobin