Exogenous estrogen preparations may have different effects on heart fat accumulation and development of coronary artery calcification (CAC) in early menopausal women, according to study results published in the Journal of the American Heart Association. Although oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, the use of transdermal 17β-estradiol (E2) may increase progression of CAC.
Previous studies have reported that heart fat volumes are larger in postmenopausal than premenopausal women. Fat deposits in the heart can be identified within the pericardial sac, in epicardial adipose tissue, or in paracardial adipose tissue, located outside the pericardial sac. As heart fat may contribute to coronary arterial disease, these deposits can serve as risk markers for cardiovascular disease.
The effects of exogenous estrogen use on cardiovascular risk is controversial. In this study, researchers aimed to assess the effects of oral and transdermal estrogen formulations on heart fat and the effect of these preparations on CAC progression in women in early menopause.
This was a secondary analysis of data from KEEPS (Kronos Early Estrogen Prevention Study; ClinicalTrials.gov Identifier: NCT00154180), a multicenter randomized placebo-controlled trial to assess the effects of conjugated equine estrogens and transdermal E2 on progression of atherosclerosis. The study recruited 727 women aged 42 to 58 years, between 6 and 36 months from last menses, who were followed for 48 months.
In the current analysis, all participants without heart fat and CAC measurements were excluded. The cohort included 474 patients (mean age, 52.7±2.6 years) with available computed tomography-based heart fat and CAC measurements at baseline and 48 months. In total, 143 women (30.2%) received oral conjugated equine estrogen, 145 (30.6%) received transdermal E2, and 186 (39.2%) received placebo.
The changes in paracardial and epicardial adipose tissue were not significantly different across treatment groups. Although in the placebo group there was a significant increase in epicardial adipose tissue, it did not increase in the conjugated equine estrogens group and increased only marginally in the transdermal E2 group. Paracardial adipose tissue did not change in any study group.
In women receiving conjugated equine estrogens, the risk of developing an increase in epicardial adipose tissue was lower compared with women in the placebo group (odds ratio, 0.62; 95% CI, 0.40-0.97; P =.03).
CAC progression was documented in 14% of study participants, but changes in epicardial and paracardial adipose tissue were not significantly associated with this progression. However, treatment type modified the association between changes in paracardial adipose tissue and progression of CAC in the transdermal hormone therapy group. Increases of paracardial adipose tissue with use of transdermal E2 were associated with CAC progression, but the same was not true for oral conjugated equine estrogens.
The researchers noted that the study had several limitations, including some imposed by the design of KEEPS, missing data, and inability to readily generalize the findings to other populations or treatment regimens.
“We reported differential effects of [hormone therapy] use on heart fat depots in recently menopausal women. Use of [oral conjugated equine estrogens] may slow [epicardial adipose tissue] accumulation, whereas [transdermal E2] appears to augment the association between [paracardial adipose tissue] accumulation and CAC progression,” concluded the researchers.
El Khoudary SR, Zhao Q, Venugopal V, et al. Effects of hormone therapy on heart fat and coronary artery calcification progression: secondary analysis from the KEEPS trial. J Am Heart Assoc. 2019;8:e012763.