Greater IL-6, D-dimer, and ICAM-1 Levels Are Associated With Lower Small HDL Particle Concentration in the Multicenter AIDS Cohort Study

In HIV-infected men, both untreated and on antiretroviral therapy, and in HIV-uninfected men, greater interleukin-6 (IL-6), D-dimer, and intercellular adhesion molecule-1 (ICAM-1) levels are associated with lower small HDL particle number (HDL-P), and greater IL-6 and ICAM-1 levels are associated with lower total HDL-P.
Objective Low HDL cholesterol (HDL-C) is common in people living with HIV infection, which is associated with inflammation, and correlates with greater cardiovascular disease (CVD) risk. Particles of HDL are HDL subfractions, and in some general population studies, higher small HDL particle number (HDL-P) has been associated with lower CVD risk. The objective of this study was to determine whether HIV serostatus and systemic inflammation were associated with small HDL-P in the Multicenter AIDS Cohort Study (MACS). Method The MACS is composed of HIV-infected and HIV-uninfected men. Separate linear regression analyses were conducted to evaluate the associations between outcomes (small HDL-P, large HDL-P, total HDL-P, and HDL size) and variables of interest (interleukin-6 [IL-6], D-dimer, and intercellular adhesion molecule-1 [ICAM-1] levels), with adjustment for other CVD risk factors. Results The study population included 553 HIV-infected (88.1% on current ART) and 319 HIV-uninfected men. The mean age was 52.7 years for HIV-infected men and 55.3 years for HIV-uninfected men. In separate models of the study population, higher log IL-6 was associated with lower total and small HDL-P (P < .01 for both), independent of HIV serostatus and CVD risk factors. Similar results were seen with ICAM-1. Positive HIV serostatus was associated with lower small and total HDL-P, adjusted for inflammatory markers. Conclusions Greater systemic inflammation and HIV infection both were associated with lower atheroprotective small HDL-P. This may be a potential mechanism contributing to increased cardiovascular risk among HIV-infected people.