Menopausal Symptoms and Cardiovascular Disease Risk Indices Among Women With HIV
Authors: Toribio Mabel , Fulda Evelynne S , Chu Sarah M , Drobni Zsofia D , Awadalla Magid , Cetlin Madeline , Stanley Takara L , North Crystal M , Nelson Michael D , Jerosch-Herold Michael , Szczepaniak Lidia S , Burdo Tricia H , Looby Sara E , Neilan Tomas G , Zanni Markella V 
Published: May 2021

Abstract
Background: Women with HIV (WWH) (vs. women without HIV) have an increased risk of cardiovascular disease (CVD) in relation to heightened systemic immune activation/inflammation. Moreover, WWH show evidence of advanced reproductive aging and unique patterns of hot flash symptomatology. General population studies have revealed that hot flashes may relate to surrogate markers of CVD risk. The relationship between hot flashes and immune activation as well as subclinical cardiac pathology among WWH has not been previously investigated.
Methods: In a prospective, cross-sectional study, 23 WWH on anti-retroviral therapy and 19 women without HIV (ages 40–75), group-matched on age and BMI, were enrolled and completed reproductive health assessments, immune phenotyping and cardiovascular MRI. Women without prior CVD or diabetes were eligible.
Results: Women were similar in age and BMI (WWH vs. women without HIV: 51 ± 5 vs. 52 ± 6 years, P=0.79 and 32 ± 8 vs. 31 ± 7 kg/m2, P=0.71). There was no significant between-group difference in the percentage of women without menses in the past year (p=0.52) or in the percentage of women with undetectable levels of anti-mullerian hormone (p=0.71). No women in either group were on estrogen and/or progesterone for treatment of menopausal symptoms. Hot flash frequency (days per week with hot flashes) was higher among WWH versus women without HIV (median [IQR], 7.0 [1.3, 7.0] vs. 0.8 [0.0, 2.1], p=0.01). In sensitivity analyses excluding either women with menses in the past year or with detectable AMH, WWH still reported a significantly higher number of days per week with hot flashes (7.0 [6.3, 7.0] vs. 0.4 [0.0, 2.3], p=0.007, and 7.0 [2.4, 7.0] vs. 0.8 [0.0, 2.1], p=0.01, respectively). Among WWH experiencing (vs. not experiencing) hot flashes in the past year, longer duration of ART use was noted (21.2 [16.0, 22.7] vs. 9.3 [3.3, 16.0] years, p=0.03). Among the entire cohort and among WWH, women with more than one hot flash per day had higher levels of soluble CD14, a marker of monocyte activation, compared to women with one or fewer hot flash per day (p=0.004 and p=0.02, respectively). Among WWH and a history of hot flashes, years since onset of hot flashes related to cardiovascular MRI-derived measures of subclinical pathology. Specifically, years since onset of hot flashes related directly to myocardial steatosis (intramyocardial triglyceride content; ρ=0.80, p=0.02) and inversely to diastolic function (left atrial passive ejection fraction; ρ=─0.70, p=0.03).
Conclusions: WWH experienced a higher frequency of hot flashes compared to women without HIV. Among WWH, hot flash symptomatology related to systemic immune activation and to cardiovascular MRI-derived measures of CVD risk. Additional research is required to improve understanding of mechanisms underlying these relationships and determine if hot flashes are a sex-specific risk factor for CVD in WWH.