Sex-Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation among People with HIV in the U.S.
Academic Article
Overview
abstract
BACKGROUND: August Among people with HIV (PWH), sex-differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. METHODS: REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of U.S. participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (N = 755 CTA; N = 725 CTA + immune). We characterized sex-differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. RESULTS: The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median 4.9% vs. 2.1%), while obesity rates were higher among females (48% vs. 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors [RR(95% CI) for any plaque 0.67 (0.50, 0.92); RR for NC/V-P 0.71 (0.51, 1.00) (adjusted for ASCVD risk score and BMI)]. Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < 0.001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < 0.02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = 0.055). CONCLUSIONS: Among U.S. PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer, but not other tested parameters. PREVIOUS PRESENTATION: Conference on Retroviruses and Opportunistic Infections (CROI), 2022; International Workshop on HIV and Women (IWHW), 2022; AIDS Clinical Trials Group Network Meeting, 2022; REPIREVE State of the Science Meeting, 2022. CLINICALTRIALS.GOV IDENTIFIER: NCT0234429 (date of initial registration: January 22, 2015).
