Lipoprotein(a) and HIV

Abstract

Objective In the general population, lipoprotein(a), Lp(a), has been established as an independent causal risk factor for cardiovascular disease (CVD). Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a), apo(a), gene. The roles of Lp(a)/apo(a) in HIV-related elevated CVD risk remain unclear. Approach and Results The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness (cIMT) were assessed in 150 HIV-infected and 100 HIV-uninfected women in the Women’s Interagency HIV Study. Linear regression analyses with and without adjustments were used. The cohort was young (mean age: ~31 years) with the majority being African-Americans (~70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (p=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (p=0.022) were significantly associated with cIMT in the HIV-infected women only. After accounting for confounders (age, race, smoking, BMI, blood pressure, HCV co-infection, menopause, plasma lipids, treatment status, CD4+ T-cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (p=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (p=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with cIMT. Conclusions Lp(a) and allele-specific apo(a) levels predict cIMT in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.

Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study

“…CVD in HIV is multifactorial in nature, resulting from a complex interplay between diverse components, such as genetic and environmental factors, as well as heightened state of systemic inflammation and immune activation intrinsic to HIV infection. In line with our previous study (21) and studies by others (39), HIV was associated with an atherogenic lipid profile (low HDL cholesterol and high triglyceride) in the current study. The impact of ART on traditional CVD risk factors, including lipid profile, has been extensively investigated in various HIV-seropositive population groups such as children and adults (across the lifespan) or males and females (40)(41)(42).…”

“…In a subsequent cross-sectional study among HIVseropositive young women enrolled in the WIHS (a different subcohort), we demonstrated a significant positive association of cIMT with both Lp(a) level and allele-specific apo(a) level determined by the smaller apo(a) size (21). To the best of our knowledge, the latter study was the first of its kind to establish a link between Lp(a) and a cardiovascular outcome in the HIV setting.…”

“…By employing this approach to HIV-seropositive cohorts, we demonstrated a higher allele-specific apo(a) level carried by atherogenic smaller apo(a) sizes in HIVseropositive individuals with a higher CD4+ T-cell count (20), and a significant positive association of allele-specific apo(a) level with carotid intima media thickness (cIMT), a measure of subclinical atherosclerosis (21). These findings suggested that HIV infection and/or ART may modulate Lp(a) level by guest, on June 8, 2019 www.jlr.org Downloaded from 5 and associated atherogenic properties.…”