Abstract
BACKGROUND: The effects of statin therapy on pericoronary adipose tissue (PCAT) and its relationship with plaque progression and outcomes in people with HIV (PWH) remain poorly understood. OBJECTIVES: The aim of this study was to evaluate PCAT density changes over time; statin effects on PCAT; and associations among PCAT changes, coronary plaque, and clinical outcomes. METHODS: In the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) mechanistic computed tomographic (CT) substudy (n = 753, mean age: 51 ± 6 years, 17% women), PCAT density was measured from noncontrast CT images at baseline and 2 years, while coronary plaque volumes (total, calcified, and noncalcified) were assessed from contrast-enhanced CT angiograms. Analyses were stratified by coronary artery disease burden (segment involvement score 0, 1-3, or ≥4) and adjusted for technical parameters, atherosclerotic cardiovascular disease risk, body mass index, inflammatory biomarkers, and statin allocation. Associations among PCAT, plaque changes, and events (all-cause mortality, major adverse cardiovascular events [MACE], and MACE or death) were evaluated. RESULTS: Baseline PCAT density was -87.7 ± 10.5 HU, increasing by 4.5 HU (95% CI: 3.8-5.2; P < 0.001) over 2 years. Pitavastatin prevented this increase in participants with segment involvement scores ≥4 (-1.7 HU vs +3.8 HU; P = 0.016, pitavastatin vs placebo, respectively). Greater PCAT density was associated with higher noncalcified plaque volume (per +10 HU, +5.0 mm(3); P = 0.075) and reduced calcified plaque progression (-3.2 mm(3); P = 0.031). Over a median of 6.3 years, 4.2% of patients died. Baseline PCAT density was independently associated with all-cause mortality (HR per +10 HU: 1.95; 95% CI: 1.03-3.69; P = 0.040), but not MACE. CONCLUSIONS: PCAT density increases over time in PWH, but pitavastatin mitigates this in those with high coronary artery disease burden. PCAT density is associated with vulnerable plaque morphology and all-cause mortality, supporting its potential as a prognostic imaging biomarker in PWH. (Randomized Trial to Prevent Vascular Events in HIV [REPRIEVE]; NCT02344290).