Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial

Samar R. El Khoudary, Qian Zhao, Vidya Venugopal, Jo Ann E. Manson, Maria M. Brooks, Nanette Santoro, Dennis M. Black, S. Mitchell Harman, Marcelle I. Cedars, Paul N. Hopkins, Ann E. Kearns, Virginia M. Miller, Hugh S. Taylor, Matthew J. Budoff

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere012763
JournalJournal of the American Heart Association
Volume8
Issue number15
DOIs
StatePublished - Aug 6 2019

Fingerprint

Coronary Vessels
Estrogens
Fats
Adipose Tissue
Hormones
Conjugated (USP) Estrogens
Placebos
Therapeutics
Estradiol
Menopause
Atherosclerosis
Randomized Controlled Trials
Odds Ratio
Clinical Trials

Keywords

  • coronary artery disease
  • epicardial fat
  • estrogen
  • menopause

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

El Khoudary, S. R., Zhao, Q., Venugopal, V., Manson, J. A. E., Brooks, M. M., Santoro, N., ... Budoff, M. J. (2019). Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial. Journal of the American Heart Association, 8(15), [e012763]. https://doi.org/10.1161/JAHA.119.012763

Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression : Secondary Analysis From the KEEPS Trial. / El Khoudary, Samar R.; Zhao, Qian; Venugopal, Vidya; Manson, Jo Ann E.; Brooks, Maria M.; Santoro, Nanette; Black, Dennis M.; Harman, S. Mitchell; Cedars, Marcelle I.; Hopkins, Paul N.; Kearns, Ann E.; Miller, Virginia M.; Taylor, Hugh S.; Budoff, Matthew J.

In: Journal of the American Heart Association, Vol. 8, No. 15, e012763, 06.08.2019.

Research output: Contribution to journalArticle

El Khoudary, SR, Zhao, Q, Venugopal, V, Manson, JAE, Brooks, MM, Santoro, N, Black, DM, Harman, SM, Cedars, MI, Hopkins, PN, Kearns, AE, Miller, VM, Taylor, HS & Budoff, MJ 2019, 'Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial', Journal of the American Heart Association, vol. 8, no. 15, e012763. https://doi.org/10.1161/JAHA.119.012763
El Khoudary, Samar R. ; Zhao, Qian ; Venugopal, Vidya ; Manson, Jo Ann E. ; Brooks, Maria M. ; Santoro, Nanette ; Black, Dennis M. ; Harman, S. Mitchell ; Cedars, Marcelle I. ; Hopkins, Paul N. ; Kearns, Ann E. ; Miller, Virginia M. ; Taylor, Hugh S. ; Budoff, Matthew J. / Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression : Secondary Analysis From the KEEPS Trial. In: Journal of the American Heart Association. 2019 ; Vol. 8, No. 15.
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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.",
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T2 - Secondary Analysis From the KEEPS Trial

AU - El Khoudary, Samar R.

AU - Zhao, Qian

AU - Venugopal, Vidya

AU - Manson, Jo Ann E.

AU - Brooks, Maria M.

AU - Santoro, Nanette

AU - Black, Dennis M.

AU - Harman, S. Mitchell

AU - Cedars, Marcelle I.

AU - Hopkins, Paul N.

AU - Kearns, Ann E.

AU - Miller, Virginia M.

AU - Taylor, Hugh S.

AU - Budoff, Matthew J.

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N2 - 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.

AB - 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.

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