Complexity of the relation between hemoglobin A1C, diabetes mellitus, and progression of coronary narrowing in postmenopausal women.

The aim of this study was to assess the effect of diabetes mellitus (DM) and glycosylated hemoglobin (HbA1c) on the progression of atherosclerosis in postmenopausal women. A retrospective analysis of the Women's Angiographic and Vitamin and Estrogen (WAVE) trial, a multicenter randomized trial on progression of atherosclerosis in postmenopausal women, was performed. Baseline and follow-up angiography was performed in 320 women. Minimum luminal diameter and average luminal diameter at baseline and follow-up were measured in 1,735 coronary segments. Measurements and adverse events were grouped on the basis of history of DM and HbA1c. DM was associated with more total cardiac events but with similar rates of death or myocardial infarction. There were greater reductions in minimum luminal diameter and average luminal diameter in segments from patients with known DM (p <0.001) and with a baseline HbA1c ≥6.5% (p = 0.002 and p = 0.004, respectively). The greater reductions in minimum luminal diameter and average luminal diameter in the higher HbA1c strata were only in patients with known DM. More new lesions, however, appeared with baseline HbA1c ≥5.7%, irrespective of a history of DM. In conclusion, the relation between DM and the progression of coronary narrowing in postmenopausal women is complex. Clinically apparent DM, not elevated HbA1c alone, appears to promote the progression of established coronary lesions even in HbA1c ranges diagnostic of pre-DM and DM. This raises the possibility that coronary narrowing of existing stenosis in women with DM may be due to negative remodeling, a complex process that might be less dependent on hyperglycemia than new lesion formation.