@article{a2cf4af73c404a2f92b40846ce07c2e1,
title = "Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial",
abstract = "Background: Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results: KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and <100 and annualized change in CAC score was ≥10. Of 727 KEEPS participants, 474 (mean age: 52.7 [SD: 2.6]; 78.1% white) had computed tomography–based heart fat and CAC measures at both baseline and 48 months. Compared with women on placebo, women on oral conjugated equine estrogens were less likely to have any increase in epicardial adipose tissue (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40–0.97]; P=0.03). PAT did not change in any group. Changes in epicardial adipose tissue and PAT did not differ by treatment group. CAC increased in 14% of participants. The assigned treatment modified the association between PAT changes and CAC progression (P=0.02) such that PAT increases were associated with CAC increases only in the transdermal 17β-estradiol group. Conclusions: In recently menopausal women, oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, whereas transdermal 17β-estradiol may increase progression of CAC associated with PAT accumulation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00154180.",
keywords = "coronary artery disease, epicardial fat, estrogen, menopause",
author = "{El Khoudary}, {Samar R.} and Qian Zhao and Vidya Venugopal and Manson, {Jo Ann E.} and Brooks, {Maria M.} and Nanette Santoro and Black, {Dennis M.} and Harman, {S. Mitchell} and Cedars, {Marcelle I.} and Hopkins, {Paul N.} and Kearns, {Ann E.} and Miller, {Virginia M.} and Taylor, {Hugh S.} and Budoff, {Matthew J.}",
note = "Funding Information: Role of the Sponsors: The Aurora Foundation, Bayer HealthCare, Abbott Pharmaceuticals, and Pfizer Pharmaceuticals had no input into the design or conduct of the study or the writing, review, or approval of this article. We gratefully acknowledge the dedicated efforts of all the investigators and staff at the KEEPS (Kronos Early Estrogen Prevention Study) clinical centers, the KEEPS Data Coordinating Center at the Kronos Longevity Research Institute, and the National Institutes of Health institutes supporting ancillary studies. Above all, we recognize and thank the KEEPS participants for their dedication and commitment to the KEEPS research program. Funding Information: KEEPS (Kronos Early Estrogen Prevention Study) was funded by grants from the Aurora Foundation to the Kronos Longevity Research Institute (S.M.H. and F.N., co‐PIs); from the National Institutes of Health (NIH) HL90639 to V.M.M. and R21 NS066147 to K.K.; and from the Mayo Clinic (Clinical and Translational Science Award [CTSA] UL1 RR024150), the Mayo Foundation, Brigham and Women's Hospital/Harvard Medical School CTSA UL1 RR024139, and University of California, San Francisco CTSA UL1 RR024131 from the National Center for Advancing Translational Sciences, a component of the NIH and NIH Roadmap for Medical Research. The Pfizer Company supported poststudy hormone measurements. Study medications were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals. KEEPS Heart Fat ancillary study: NHLBI R21 HL140011 to El Khoudary, NIH HL094581 to Wildman. The article contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Advancing Translational Sciences or the National Institutes of Health. Funding Information: El Khoudary reports grant support from NHLBI HL140011; Santoro reports consulting work for Menogenix (scientific advisory board, stock options) and Astellas/Ogeda (scientific advisory board); Miller reports grant support from NIH U54 AG44170 and the Mayo Foundation for Research and Education. The remaining authors have no disclosures to report. Publisher Copyright: {\textcopyright} 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.",
year = "2019",
month = aug,
day = "6",
doi = "10.1161/JAHA.119.012763",
language = "English (US)",
volume = "8",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "15",
}