Written by Joyce Smith, BS. This study provides information which adds to existing data that various hormone therapy (HT) regimens may contribute to or protect against the deposition of heart fat and CVD risk.
Heart fat is associated with coronary arterial disease risk factors, CVD events, and all-cause mortality 1,2. Postmenopausal women have a larger volume of heart fat than premenopausal women 3 and endogenous estrogen may regulate these fat depots. Heart fat depots can be either epicardial adipose tissue (EAT) which covers the heart in the pericardial sac 3 or paracardial adipose tissue (PAT) which occurs outside the pericardial sac 4,5. Lower levels of estrogen, specifically estradiol, are associated with more PAT accumulation 3. The amount of heart fat accumulation in EAT and PAT may serve as non-invasive risk markers for coronary artery disease (CAD) in postmenopausal women.
KEEPS is a multicenter, randomized, placebo-controlled trial 6 designed to compare the effects of oral conjugated equine estrogens (o-CEE) and transdermal 17b-estradiol (t-E2) to placebo, and to examine HT’s effect on the progression of subclinical atherosclerosis over a 48 month period. The research team specifically examined the effect of HT on heart fat accumulation and the extent to which HT formulations impact the association between heart fat depots and coronary artery calcification (CAC). The analysis included 467 early menopausal women with an intact uterus and who had their last period 6 to 36 months prior. All women had plasma estradiol levels under 147 pmol/L and/or follicle-stimulating hormone levels of 35 IU/L or higher. Excluded were women with obesity, those who were heavy smokers, or those who had cardiovascular disease, higher cholesterol, or uncontrolled hypertension. In addition to oral conjugated equine estrogens (0.45 mg/d) or transdermal estradiol (50 µg/d), women were given 200 mg daily of oral micronized progesterone for the initial 12 days. Carotid intima-media thickness was measured with the far wall of the distal common carotid artery.
CAC progression occurred in 14% of the study participants. Women who had CAC progression were more likely to be less educated, to have spent a longer time in menopause, and to have higher triglycerides, insulin, and insulin resistance indexes compared with women who did not show CAC progression. This study results suggest that the use of oral and dermal estrogen by early menopausal women affects quite differently their accumulation of heart fat and its association with CAC. EAT did not increase in the o-CEE group, increased only marginally in the t-E2 group, and increased significantly in the placebo group. PAT did not change in any group. No significant differences existed in PAT or EAT changes across treatment groups. Early menopausal women on o-CEE had no changes in EAT volume over the 48 months of treatment when compared to the placebo group of women whose EAT increased over time (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40– 0.97]; P=0.03). PAT remained unchanged in all three treatment groups.
Researchers conclude that while o-CEEs may slow down EAT tissue accumulation, t-E2 appears to be the driver that may increase the association between PAT accumulation and CAC progression. They emphasize that EAT and PAT are metabolically distinct adipose tissue depots that should be evaluated separately when assessing the roles they play in CVD risk. Because HT remains the best therapeutic option for the relief of debilitating menopausal symptoms 7, clinicians recommend that HT prescriptions be customized for each patient, always using the best available evidence to provide maximum patient benefit with minimum patient risk 5.
A significant study limitation was the specificity of study results to the KEEPS participants, thus the types, doses and duration of HT use could not be generalized to populations outside of KEEPS.
Source: El Khoudary, Samar R., Vidya Venugopal, JoAnn E. Manson, Maria M. Brooks, Nanette Santoro, Dennis M. Black, Mitchell Harman et al. “Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial.” Menopause 27, no. 3 (2020): 255-262.
© 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.
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Posted April 5, 2021.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References
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- Mahabadi AA, Lehmann N, Kälsch H, et al. Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study. JACC Cardiovascular imaging. 2014;7(9):909-916.
- El Khoudary SR, Shields KJ, Janssen I, et al. Cardiovascular Fat, Menopause, and Sex Hormones in Women: The SWAN Cardiovascular Fat Ancillary Study. The Journal of clinical endocrinology and metabolism. 2015;100(9):3304-3312.
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- Kaushik M, Reddy YM. Distinction of “fat around the heart”. J Am Coll Cardiol. 2011;58(15):1640; author reply 1640-1641.
- El Khoudary SR, Venugopal V, Manson JE, et al. Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial. Menopause. 2020;27(3):255-262.
- North American Menopause Society. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753.
