Persons with human immunodeficiency virus (HIV) (PWH) have an approximately 2-fold increased risk of developing cardiovascular disease (CVD) than those without HIV (PWoH)1, 2. This increased CVD risk may be due to chronic systemic inflammation and immune activation in PWH3. Lipoprotein (a) (Lp(a)), a subclass of low-density lipoprotein (LDL), is an independent atherosclerotic risk factor in PWoH4, 5. While elevated Lp(a) levels may occur in PWH6, few studies have investigated the association of Lp(a) and subclinical atherosclerosis7, 8, and no studies have evaluated its association with peri-coronary inflammation.

Recently, the fat attenuation index (FAI) was developed to quantify peri-coronary inflammation by measuring perivascular fat composition and shown to correlate with peri-coronary inflammation9. In the CRISP CT study, which was a post-hoc analysis of prospective outcome data from two large cohorts, the authors found that lower (less negative) FAI values in the proximal right coronary artery (RCA) and left anterior descending artery (LAD), but not the left circumflex coronary artery, were found to independently predict atherosclerotic CVD (ASCVD) risk in PWoH, illustrating the spatially heterogeneous process of atherosclerosis10. Some investigators have suggested that FAI is a more robust predictor of coronary artery inflammation and early atherosclerosis than the coronary calcium score, which is determined by structural changes that occur later in the atherosclerotic process9. To this end, our group initiated a longitudinal cohort study to characterize FAI in PWH on ART as well as in PWoH11.

Based upon prior associations of Lp(a) with soluble inflammatory markers12, monocytes13, 14, and T lymphocyte subsets15 in PWoH, the current cross-sectional analysis was designed to investigate the association between baseline FAI and plasma levels of Lp(a) in PWH and PWoH, and the extent to which Lp(a) levels may be correlated to markers of inflammation and immune cell activation. We hypothesized that Lp(a) would be associated with increased peri-coronary inflammation and correlated with systemic inflammation and monocyte and T cell activation in PWH.