Background
A high prevalence of imaging markers of cerebrovascular disease has been observed in PWH despite viral suppression on ART. Little is known about whether the burden of subclinical cerebrovascular injury differs by sex. We compared cerebral small vessel disease (SVD) and large artery disease (LAD) and examined differential effects of modifiable factors on cerebrovascular injury in female and male participants with HIV from the MACS/WIHS Combined Cohort Study.
Methods
Participants on ART at moderate to high risk of cardiovascular disease (CVD) were enrolled at 3 U.S. sites and underwent comprehensive cerebrovascular imaging by brain MRI, MR angiogram (MRA) with vessel wall imaging (VWI), and phase-contrast 4D flow of the intracranial arteries. We quantified white matter hyperintensity (WMH) volume with an open-source automated lesion segmentation tool for Statistical Parametric Mapping. A radiologist blinded to all participant data assigned an SVD score based on visual rating of WMH, microbleed and lacunar infarct count. LAD was scored on presence of luminal stenosis on MRA and enhancement pattern on VWI. We constructed linear regression models to estimate separate and interactive associations of risk factors with sex on log-transformed measures of cerebrovascular injury.
Results
151 PWH (mean age 56 years, 55% female, 41% Black, 31% White) were included. Female participants were more likely to have hypertension, higher BMI, more depressive symptoms, less physical activity, and to be current smokers. The burden of SVD (281.5%, 95% CI 72.9%-742.0%, p=0.001) but not LAD (16.2%, 95% CI 44.0%-141.1%, p=0.69) was higher in female participants, independent of age, race, CVD and other risk factors. We observed significant 2-way interactions between sex*viremia (0.9% per 100 copies/mL, 95% CI 0.0%-1.8%, p=0.044) & sex*injection drug use (286.7%, 95% CI 27.2%-1075.2%, p=0.017), which were associated with excess WMH for female participants, and between sex*physical activity (-65.7%, 95% CI -86.2% to -14.5%, p=0.022) & sex*prior smoking (-57.6%, 95% CI -82.3%-1.5%, p=0.054), which were more protective against SVD for female participants.
Conclusions
The effect of modifiable factors on cerebrovascular injury differed by sex. Factors that were more protective against SVD for female participants were also less common among female participants (e.g., physical activity). Targeting these modifiable factors could narrow the cerebrovascular risk gap observed in female participants with HIV.