Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons with HIV


 
 
 There is an incompletely understood increased risk for cardiovascular disease (CVD) among people living with HIV (PLWH). We investigated if a collection of biomarkers were associated with CVD among PLWH. Mendelian randomization (MR) was used to identify potentially causal associations.
 
 
 
 Data from follow-up in 4 large trials among PLWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted.
 
 
 
 Univariate analysis found CLEC6A, HGF, IL6, IL10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (OR = 1.48, p = 0.037), HGF (OR = 1.83, p = 0.012) and IL6 (OR = 1.45, p = 0.016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL6RA, and SCGB3A2.
 
 
 
 These results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PLWH (IL6 and its receptor), some are novel to PLWH (HGF, AXL and GAS6) and some are novel overall (CLEC6A). Further investigation into; 1.) the uniqueness of these biomarkers in PLWH and 2.) the role of these biomarkers as targets among PLWH, is warranted.
