Abstract 3771: Type of Menopause, Hormone Therapy and Coronary Artery Disease in Women: New Insights from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Background. While menopausal hormone therapy (HT) appears protective for coronary artery disease (CAD) in animal oophorectomy models and human epidemiological studies, recent clinical HT trial results have not demonstrated benefit; however prior studies have not carefully characterized ovarian function and menopause.
Methods. We prospectively studied 654 postmenopausal women undergoing coronary angiography for suspected ischemia and enrolled in the WISE study. Type of menopause and HT use (assessed by WISE reproductive questionnaire), coronary artery disease severity (assessed by the WISE core angiography laboratory), and adverse CV events (defined as death, myocardial infarction, heart failure hospitalization, or stroke) over a median of 6 years were evaluated.
Results. Mean age was 62 years, 16% were non-white, 42% had obstructive CAD (≥ 50% stenosis), 134 (20%) had surgical menopause, and 150 (23%) had a major adverse CV event. In women with natural menopause, HT use was associated with less angiographic CAD (hazard ratio [95% confidence interval]: 0.38 [0.26 – 0.54], p<0.0001) and fewer major adverse CV events (0.67 [0.47– 0.96], p=0.03). Among women with surgical menopause, HT use was not related to angiographic CAD (1.08 [0.43–2.71], p=0.47) or CV events (1.68 [0.50 –5.58], p=0.40). Naturally menopausal women initiating HT use prior to age 45 had a greater reduction of CAD compared to those initiating HT after age 45 or those not using HT. No differences by age of HT initiation were found in surgically menopausal women. Analysis of relevant covariates and adjustment for age and health risk factors suggested that some of the benefit was attributable to healthy user factors, although a significant beneficial association remained for HT following adjustment for these variables (p=0.001).
Conclusions. While some of the protective relationship for CAD observed for HT in naturally menopausal women is attributable to a healthy user effect, a significant residual association remains, and earlier initiation of HT was associated with a greater benefit. There was no protective association observed for HT in the surgically menopausal women. This analysis sheds light on prior data discrepancies, and may be useful for prospective HT clinical trial planning.