Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial

Abstract

Objective: Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial.

Methods: KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17β-estradiol (t-E2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by computed tomography.

Results: In all, 467 women (mean age [SD] 52.7 [2.5]; 78.2% White; 30% on o-CEE, 30.8% t-E2, 39.2% placebo) with heart fat volumes and CIMT at baseline and 48 months were included. EAT and PAT changes were not associated with CIMT progression; however, the assigned treatment significantly modified the association between PAT (but not EAT) change and CIMT progression. In the o-CEE group, adjusted CIMT progression was 12.66 μm (95% confidence interval [CI] 1.80, 23.52) lower than in t-E2 group (P = 0.02), and 10.09 μm (95% CI 0.79, 19.39) lower than in placebo group (P = 0.03), as per 1-SD increase in PAT.

Conclusion: Compared with t-E2, o-CEE appears to slow down the adverse effect of increasing PAT on progression of atherosclerosis. Whether this beneficial association is specific to CEE or to the oral route of CEE administration is unclear and should be assessed further.

Trial registration: ClinicalTrials.gov NCT00154180.

Conflict of interest statement

Conflicts of interest/financial disclosures: Samar El Khoudary: No | Vidya Venugopal: No | JoAnn Manson: No | Maria Brooks: No | Nanette Santoro: Yes; Menogenix:stock options: scientific advisory board; Astellas/Ogeda: scientific advisory board: scientific advisory board | Dennis Black: No | Mitchell Harman: No | Howard N. Hodis: NIH and TherapeuticsMD| Eliot A. Brinton: Has received funding from Amarin and NovoNordisk | Virginia Miller: No | Hugh Taylor: Dot Labs, Abbvie | Matthew Budoff: Yes; Grant Support from NIH and General Electric: grant support to my institution.

Figures

Figure 1.

CONSORT Flow Diagram of the Analytical Sample from the KEEPS-Heart FAT Ancillary Study Abbreviations: o-CEE: oral conjugated equine estrogen; t-E2: transdermal