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Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus
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CID 29 July 2022 - Brandilyn A. Peters,1, David B. Hanna,1 Anjali Sharma,2 Kathryn Anastos,2 Donald R. Hoover,3 Qiuhu Shi,4 Caitlin A. Moran,5 Elizabeth A. Jackson,6 Maria L. Alcaide,7 Igho Ofotokun,5 Adaora A. Adimora,8 Sabina A. Haberlen,9 Mardge Cohen,10 Phyllis C. Tien,11,12 Katherine G. Michel,13 Steven R. Levine,14 Howard N. Hodis,15 Robert C. Kaplan,1,16 and Michael T. Yin17
better menopause care including HT use has recently been encouraged for women with HIV, with providers urged to review indications, contraindications, and risk of adverse events with patients [10].
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
better menopause care including HT use has recently been encouraged for women with HIV, with providers urged to review indications, contraindications, and risk of adverse events with patients [10].
Abstract
Background
Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks.
Methods
Among 609 postmenopausal women (1234 person-visits) in the Women’s Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.
Results
Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
Conclusions
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
Estrogen-based menopausal hormone therapy (HT) has been the subject of controversy regarding its effects on cardiovascular disease (CVD). While many observational studies of recently postmenopausal women have shown reduced rates of coronary heart disease (CHD) in HT users [1], the Women’s Health Initiative (WHI) randomized trials of the 1990s demonstrated increased CHD and stroke with HT use, leading to concerns of harm and widespread declines in HT prescriptions [2]. The discrepancy between the WHI trials, conducted among older women, and observational studies of women in early menopause, led to the HT timing hypothesis—that effects of HT depend on timing of initiation in relation to menopause [3]. Substantial evidence has accumulated supporting the protective effect of HT on cardiometabolic endpoints among women <60 years old when initiated within 10 years of menopause [2-5].
CVD is a particular concern in women with HIV, as HIV infection is associated with increased CVD, more so in women than men [6]. Persistent immune activation in people with HIV may contribute to elevated risk of non-AIDS diseases, including CVD [7], despite antiretroviral therapy. Perturbations in sex hormones in women with HIV may also contribute to CVD risk [8]. HT uptake for menopausal symptoms in women with HIV is very low [9], with a key barrier being lack of knowledge of the effect of HT on CVD in women with HIV [10]. Here, we examine the relationship of menopausal HT with subclinical atherosclerosis and blood immune activation biomarkers in the Women’s Interagency HIV Study (WIHS). Additionally, given concerns regarding increased risk of venous thromboembolism (VTE) with HT, we also assessed the relationship of HT to serum D-dimer, a biomarker of thrombosis associated with VTE risk in women taking HT [11].
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