Plasma monocyte chemoattractant protein-1 and tumor necrosis factor-α levels predict the presence of coronary artery calcium in HIV-infected individuals independent of traditional cardiovascular risk factors

Abstract

Coronary artery calcium (CAC) is a validated subclinical measure of atherosclerosis. Studies in the general population have linked blood inflammatory biomarkers including monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor (TNF)-α with the burden of CAC, but this relationship is often lost following correction for traditional cardiovascular risk factors. We assessed the relationship of various biomarkers to CAC, specifically in HIV-infected individuals on potent antiretroviral therapy (ART). Analyses utilized entry data from participants in the Hawaii Aging with HIV-Cardiovascular (HAHC-CVD) study. Computerized tomography examinations for CAC were obtained locally and analyzed by a central reading center in blinded fashion. Plasma biomarkers were assessed by multiplexing using Milliplex Human Cardiovascular Disease panels. Among a cohort of 130 subjects [88% male, median (IQR) age of 51 (46-57) years, CD4 count of 492 (341-635) cells/mm(3), 86.9% with HIV RNA ≤50 copies/ml], CAC was present in 46.9% of subjects. In univariate analyses higher levels of log-transformed MCP-1 and TNF-α were associated with the presence of CAC (p<0.05). In multivariate logistic regression models, MCP-1 and TNF-α remained significant after adjustment for traditional cardiovascular (CVD) risk factors. Similar results were found when analyses were assessed by Framingham risk score categories or when restricted to subjects with plasma HIV RNA ≤50 copies/ml. In contrast to findings in the general population, higher MCP-1 and TNF-α predict the presence of CAC independent of traditional CVD risk factors in HIV-infected subjects fully suppressed on ART, suggesting that HIV-mediated immune activation may play a role in CVD risk.