Abstract 267: Histomorphometric Evaluation of Estrogen Effects on Coronary Artery Atherosclerosis: Inhibition of Plaque Formation, Reduction in Plaque Size and Promotion of Positive Remodeling Independent of Plaque Complications
Introduction: Whether and to what extent postmenopausal estrogen therapy has beneficial effects on progression of coronary artery atherosclerosis is controversial. In previous studies with monkey models we have shown that the stage of plaque progression modulates estrogen benefits and have led to the “timing hypothesis”. In this study, we used a histomorphometric approach to understand better the effects of estrogen therapy on critical components of atherosclerosis pathogenesis. Our hypothesis was that estrogen therapy would inhibit the initial development of atherosclerotic plaques, result in smaller but not less complicated plaques and among subjects that developed plaques, it would promote positive arterial remodeling.
Methods: Forty-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomly assigned to receive no treatment (CTL) or a women’s equivalent dose of conjugated equine estrogen (CEE) (0.45 mg/day). The experimental period lasted for 20 months (equivalent to 5 years in humans). At the end of the experiment, prevalence of atherosclerotic plaques was determined. From those monkeys with affected arteries, plaque extent, severity and prevalence of stenosis were determined.
Results: Prevalence: The CEE treated group had significantly fewer monkeys with coronary artery atherosclerosis compared to the CTL group (CTL: 57 % vs. CEE: 33 % p=0.005). Extent: Among affected monkeys, the mean plaque size was significantly smaller in the CEE treated group compared to the CTL group (CTL: 0.30 ± 0.048 mm2 vs. CEE: 0.153 ± 0.028 mm2 p=0.015). Remodeling: The proportion of stenotic plaques was lower in the CEE group compared to the CTL group (CTL: 11.14 % vs. CEE: 1.34 % p= 0.008). Severity: CEE treatment did not have a beneficial effect on coronary artery severity (% of complicated [AHA grade≥ III] plaques- CTL: 52.34 % vs. 49.61 %, p=0.397).
Conclusions: These histomorphometric findings support previous evidence that beginning of estrogen therapy in the perimenopausal transition prevents plaque initiation. Among affected cases, estrogen treated monkeys had smaller plaques but were equally complicated. Notably, estrogen also promoted positive arterial remodeling among affected arteries.
Author Disclosures: G.C. Melendez: None. T.B. Clarkson: None.
- © 2014 by American Heart Association, Inc.