Table 3.

Summary of Studies Reporting Sex Differences for Cardiovascular Disease Among People With HIV

Author, Year [Ref]	Study Design Study Size (% PWH) No. of Men and Women	Study Population (Location, Race/Ethnicity, Age)	Outcomes Measured	Key Findings	Limitations
Hypertension
Frazier et al, 2019 [46]	Cross-sectional N = 7436 (100% PWH)5584 men, 1852 women	•\tOlder PWH receiving HIV care across the US who enrolled in the Medical Monitoring Project (national HIV surveillance program) •\t40% Black, 39% White, 17% Hispanic •\tAge range: ≥50 y	Prevalence of HTN, total cholesterol, LDL, stratified by age (50–64 vs ≥65 y) and sex	•\tWWH vs MWH had higher adjusted prevalence of HTN among those aged 50–64 y (41% vs 36%, P<.05) but not significantly among those aged ≥65 y (58% vs 50%, P=.06) •\tWWH in both age strata had a higher adjusted prevalence of elevated cholesterol than MWH (P<.05) •\tWWH in both age strata had a higher adjusted prevalence of elevated LDL than MWH (P<.05)	WWH were underrepresented. WWH were less likely to be virally suppressed than MWH. Did not include persons without HIV for comparison. Did not capture menopause status.
Kent et al, 2017 [48]	Cross-sectional N = 49 (100% PWH)36 men, 13 women	•\tPWH receiving care at the UAB 1917 HIV Clinic •\t51% White, 49% Black •\tMean age: 44 y	Sex differences in clinic and ambulatory BP values, and prevalence of ambulatory BP monitoring phenotypes stratified by race and sex	•\tMWH vs WWH had significantly higher awake SBP (127 vs 120mm Hg, P<.05) but not sleep SBP (112 vs 107mm Hg, P=.12); however, differences by sex were attenuated in adjusted analyses •\tMWH vs WWH had higher awake DBP (84 vs 77mm Hg, P<.05) and sleep DBP (69 vs 65mm Hg, P=.28); sex differences remained significant in adjusted analyses •\tThe prevalence of awake hypertension for MWH vs WWH was 47% vs 15% (P=.05)	Small sample size. Only adjusted for age, race, and education. Did not include persons without HIV for comparison. Did not capture menopause status.
Reinsch et al, 2008 [49]	Cross-sectional N = 802 (100% PWH) 669 men, 133 women	•\tPWH enrolled in HIV-HEART study cohort across central Europe •\t89% White •\tMean age: 44 y	Prevalence of PAH and sPAP with and without symptoms (sPAP assessed by Doppler echocardiography)	•\tsPAP did not significantly differ among MWH vs WWH (44.7 vs 45.3mm Hg, P=.9) •\tRatio of WWH to MWH with symptomatic elevated sPAP was 1.4:1 (P<.05) •\tRatio of MWH to WWH with asymptomatic elevated sPAP was 4.6:1 (P<.05)	Did not include persons without HIV for comparison Did not capture menopause status.
Atherosclerotic plaque
Fitch et al, 2013 [50]	Cross-sectional N = 233 (70% PWH) 143 men, 90 women	•\tWomen recruited from HIV clinics, community health centers, or areas surrounding Boston, MA •\tWomen: 64% White, 36% non-White •\tMean age: 47 y •\tMale data from separate but similar study •\tMen: 62% White, 21% Black, 11% Hispanic •\tMean age: 46 y	Group differences in absolute and percentage of calcified and noncalcified coronary artery plaque	•\tWWH had a higher proportion of coronary segments with noncalcified plaque vs MWH (75% vs 50%, P<.05) and vs men without HIV (vs 33%, P<.05) •\tSex significantly modified the effect of HIV status on plaque (P<.05), such that WWH had the greatest proportion of noncalcified plaque compared with all other HIV sex strata •\tWWH had higher levels of immune activation markers (soluble CD163 and soluble CD14) than MWH (P<.05)	Small sample size
Foldyna et al, 2018 [47]	Cross-sectional N = 145 (100% PWH) 97 men, 48 women	•\tWWH living in Boston, MA •\tMale data from separate but similar study in Boston, MA •\t62% White, 56% Black, 12% Hispanic •\tMean age: 48 y	Prevalence of subclinical coronary atherosclerotic plaque characteristics: any plaque, plaque type (calcified, noncalcified), plaque with high-risk morphology features (positive remodeling, low attenuation), and obstructive plaque	•\tWWH had lower prevalence than MWH of any subclinical coronary atherosclerotic plaque (35% vs 62%, P<.05) as well as prevalent obstructive plaque (0% vs 5%, P<.05), positively remodeled plaque (25% vs 51%, P<.05), and number of vascular segments with plaque (1.3 vs 2.1, P<.05) and positively remodeled plaque segments (0.5 vs 1.2, P<.05) •\tNo sex differences noted in prevalence or number of noncalcified plaque nor of low attenuation plaque •\tMWH vs WWH had greater adjusted odds of any coronary artery plaque (aOR, 3.8 [95% CI, 1.4–11.4]) and positively remodeled plaque (aOR, 3.7 [95% CI, 1.4–10.9])	Small sample size. Did not include persons without HIV for comparison. Did not capture menopause status.
Hanna et al, 2018 [52]	Nested cohort N = 3026 (67% PWH) 1304 men, 1722 women	•\tAdults enrolled in WIHS and MACS •\t46% Black, 34% White, 20% Hispanic •\tMedian age: 40 y (women), 50 y (men)	Effect of carotid plaque presence and arterial stiffness on all-cause mortality by sex and HIV status	•\tAmong all participants, the presence of carotid artery plaque (vs no plaque) increased the risk of all-cause mortality (aHR, 1.44 [95% CI, 1.10–1.88]) and was significantly modified by sex (P=.008) and dHIV serostatus (P<.001) •\tPlaque was associated with all-cause mortality among men (aHR, 2.19 [95% CI, 1.41–3.43]) but not among women •\tAmong PWH, the risk of all-cause mortality associated with plaque vs no plaque was greater among MWH (aHR, 1.65 [95% CI, .93–2.91]) vs WWH (aHR, 1.15 [95% CI, .78–1.71]). P=.048 for sex difference •\tAmong all participants, arterial stiffness was significantly associated with all-cause mortality among women (aHR, 1.71 [95% CI, 1.11–2.61]) but not among men (aHR, 1.08 [95% CI, .61–1.89]); among PWH, this association was attenuated (among WWH: aHR, 1.47 [95% CI, .94–2.28]; among MWH: aHR, 0.99 [95% CI, .56–1.93])	Did not capture menopause status
Myocardial infarction
Triant et al, 2007 [40]	Longitudinal cohort N = 1 048 440 (0.37% PWH) 429 868 men, 618 568 women	•\tAdults cared for at 2 academic centers in Boston, MA (RPDR) •\t66% White, 7% Hispanic, 7% Black, 0.6% Asian •\tMedian age: 39 y (persons without HIV), 38 y (PWH)	AMI rates per 1000 PY across 6 age strata stratified by sex and HIV status	•\tMen had a higher AMI rate than women overall (RR, 1.72 [95% CI, 1.68–1.77]) •\tWWH had higher AMI rates than MWH across most age strata •\tIn unadjusted analyses, WWH vs women without HIV had a higher AMI rate (12.71 vs 4.88); however, no significant difference was observed among men by HIV status (10.48 vs 11.44) •\tIn adjusted analyses, PWH vs persons without HIV had a higher AMI rate among women (aRR, 2.98 [95% CI, 2.33–3.75]) and among men (aRR, 1.40 [95% CI, 1.16–1.67])	Models reported did not adjust for smoking. Did not capture menopause status.
Durand et al, 2011 [53]	Longitudinal cohort N = 34 734 (20% PWH) 27 086 men, 7648 women	•\tPublicly insured adults in Québec, Canada. Data collected from Québec Health Insurance Board & Med-Echo database •\tNo race/ethnicity data available •\tMean age: 40 y	Hazard ratio for AMI per 1000 PY	•\tHIV was associated with increased risk of AMI among women (aHR, 3.77 [95% CI, 1.79–7.96]) and among men (aHR, 2.04 [95% CI, 1.62–2.57]). However, sex did not significantly modify the effect of HIV on AMI risk (P=.17)	Women were underrepresented. Models did not adjust for smoking, or HIV characteristics. Did not capture menopause status.
Fris-Moller et al, 2007 [43]	Longitudinal cohort N = 23 437 (100% PWH) 17 788 men, 5649 women	• PWH enrolled in the D:A:D Study (11 cohorts across 21 countries in Europe, US, Australia) •\t78% White, 17% Black, 3% Hispanic, 2% Asian •\tMedian age: 39 y	Incident MI rate	•\tMWH vs WWH had a higher MI rate in unadjusted analysis (RR, 3.27 [95% CI, 2.26–4.73]), demographically adjusted analysis (aRR, 1.91 [95% CI, 1.28–2.86]), and after further adjustment for cardiovascular risk factors (aRR, 2.13 [95% CI, 1.29–3.52]) •\tART-attributable MI risk was similar between MWH and WWH (RR, 1.13 vs 1.36, P=.40)	Did not include persons without HIV for comparison. Did not capture menopause status.
Heart failure
Butt et al, 2011 [54]	Longitudinal cohort N = 8486 (28% PWH) 8486 men, 0 women	•\tAdults enrolled in VACS Virtual Cohort and Large Health Study of Veteran Enrollees •\t39% White, 40% Black, 10% Hispanic •\tMean age: 48 y	Incidence rate and HR for HF diagnosis per 1000 PY stratified by HIV status	•\tRate of HF incidence was 7.12 per 1000 PY (95% CI, 6.90–7.34) among MWH and 4.82 per 1000 PY (95% CI, 4.72–4.91) among men without HIV •\tMWH vs men without HIV had higher rate of incident HF (aHR, 1.81 [95% CI, 1.39–2.36]) •\tMWH vs men without HIV had higher rate of incident HF (aHR, 1.96 [95% CI, 1.29–2.98]) in analyses excluding veterans with history of alcohol dependence	Women were not included. Models did not adjust for smoking or HIV characteristics.
Janjua et al, 2017 [55]	Longitudinal cohort N = 15 169 (9% PWH) 0 men, 15 169 women	•\tAdults cared for at 2 academic centers in Boston, MA (RPDR) •\tRace/ethnicity data not available •\tMean age: 59 y	Incident rate for HF hospitalization after HF diagnosis per 1000 PY	•\tIncidence of HF diagnosis was 0.27% per year among WWH and 0.07% per year among women without HIV •\tWWH vs women without HIV had a higher incidence of HF hospitalization (20 vs 8 per 1000 PY, P<.05) •\tIn adjusted analyses, WWH vs women without HIV had a higher risk of incident HF hospitalization after HF diagnosis (aHR, 2.58 [95% CI, 1.55–4.29])	Men were not included. Models did not adjust for smoking or HIV characteristics. Did not capture menopause status.
Womack et al, 2014 [56]	Longitudinal cohort N = 2187 (32% PWH) 0 men, 2187 women	•\tWomen enrolled in the VACS–Virtual Cohort •\t60% Black, 30% White •\tMean age: 44 y	Incidence rate of various cardiovascular events (AMI, unstable angina, ischemic stroke, and HF) stratified by HIV status	•\tWWH vs women without HIV had a higher crude incidence of HF (IRR, 2.5 [95% CI, 1.5–4.5]), incidence of cardiovascular events excluding HF (IRR, 2.3 [95% CI, 1.2–4.5]) •\tIn adjusted analysis, WWH vs women without HIV had a higher incidence of total cardiovascular events (aHR, 2.8 [95% CI, 1.7–4.6])	Men were not included. HF analysis did not adjust for CVD risk factors or HIV characteristics. Did not capture menopause status.
Cerebrovascular events
Chow et al, 2012 [57]	Longitudinal cohort N = 36 731 (12% PWH) 24 177 men, 12 554 women	•\tAdults cared for at 2 academic centers in Boston, MA (RPDR) •\t52% White, 22% Black, 17% Hispanic •\tMean age: 41 y	Incidence rate and HR for ischemic stroke per 1000 PY stratified by sex and HIV status	•\tWWH vs women without HIV had higher risk of ischemic stroke (HR, 2.16 [95% CI, 1.53–3.04]; aHR, 1.76 [95% CI, 1.24–2.52]) •\tMWH vs men without HIV had higher risk of ischemic stroke (HR, 1.18 [95% CI, .95–1.47]) (aHR, 1.05 [95% CI, .84–1.32]) •\tAmong persons without HIV, women vs men had lower risk of ischemic stroke (HR, 0.54 [95% CI, .46–.65]); however, risk was not significantly different by sex among PWH (HR, 0.97 [95% CI, .50–1.89])	Models did not adjust for HIV characteristics. Did not capture menopause status.
Chow et al, 2018 [58]	Longitudinal cohort N = 6933 (100% PWH) 5563 men, 1370 women	•\tART-naive PWH enrolled in multiple ACTG trials •\t40% White, 37% Black, 21% Hispanic •\tMedian age: 37 y	Incidence rate of first ever ischemic stroke or TIA per 1000 PY after ART initiation stratified by sex and age	•\tOverall, WWH vs MWH had higher risk of incident TIA/stroke (2.88 vs 1.40 per 1000 PY; aHR, 1.96 [95% CI, 1.04–3.67]) •\tWWH vs MWH had higher risk of TIA/stroke at age 40 (RR, 3.17 [95% CI, 1.45–6.93]) and at age 50 (RR, 1.94 [95% CI, 1.03–3.66]); however, this sex-differential risk attenuated among PWH ≥50 y	Did not include persons without HIV for comparison. Did not capture menopause status.
Mortality
Hanna et al, 2020 [45]	Longitudinal cohort N = 147 915 (100% PWH) 108 083 men, 39 832 women	•\tPWH in New York City HIV Surveillance and Vital Statistics Registries •\t44% Black, 33% Hispanic •\tMedian age: 45 y	CVD mortality per 1000 PY over 11 y of follow-up stratified by sex and neighborhood poverty level	•\tIn unadjusted analyses, women had a higher CVD mortality risk associated with HIV status (RR, 2.24 [95% CI, 2.07–2.43]) than men (RR, 1.23 [95% CI, 1.16–1.30]) •\tIn adjusted analyses, women had a higher CVD mortality risk associated with HIV status (aRR, 1.73 [95% CI, 1.62–1.85]) than men (aRR, 1.20 [95% CI, 1.15–1.26]) overall and within poverty strata •\tSex significantly modified the effect of HIV on CVD mortality (P < .05 for HIV∗sex interaction) within all poverty strata	Analyses did not control for lifestyle factors. Did not capture menopause status

Abbreviations: ACTG, AIDS Clinical Trial Group; aHR, adjusted hazard ratio; AMI, acute myocardial infarction; aOR, adjusted odds ratio; aRR, adjusted rate ratio; ART, antiretroviral therapy; BP, blood pressure; CI, confidence interval; CVD, cardiovascular disease; D:A:D, Data Collection on Adverse Events of Anti-HIV Drugs Study; DBP, diastolic blood pressure; HF, heart failure; HR, hazard ratio; HTN, hypertension; IRR, incidence rate ratio; LDL, low-density lipoprotein; MA, Massachusetts: MACS, Multicenter AIDS Cohort Study; MI, myocardial infarction; MWH, men with HIV; PAH, pulmonary arterial hypertension; PWH, persons with HIV; PY, person-years; RPDR, Research Patient Data Registry; RR, rate ratio; SBP, systolic blood pressure; sPAP, systolic pulmonary arterial pressure; TIA, transient ischemic attack; UAB, University of Alabama at Birmingham; US, United States; VACS, Veterans Aging Cohort Study; WIHS, Women’s Interagency Health Study; WWH, women with HIV.