Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection
Suman Kundu, Matthew S. Freiberg, Russell P. Tracy, Kaku So‐Armah, John R. Koethe, Meredith S. Duncan, Hilary A. Tindle, Joshua A. Beckman, Matthew J. Feinstein, Wyatt J. McDonnell, Amy C. Justice, Margaret F. Doyle
Abstract
Lower CD4+ cell count in people with HIV infection (PWH) is associated with increased cardiovascular disease (CVD) risk. Whether subsets of CD4+ T helper cells are linked with CVD is unclear. The aim of this study was to explore the association between peripherally circulating CD4+ T cell subsets and incident CVD. Data from 1,860 participants (1,270 PWH) without prevalent CVD from the VACS (Veterans Aging Cohort Study), a prospective, observational cohort of veterans with and without HIV infection, were analyzed. T cell subsets were quantified in baseline samples using flow cytometry. Incident CVD events were identified using International Classification of Diseases-9th Revision and International Classification of Diseases-10th Revision diagnosis and procedure codes. Participants were followed from baseline date (2005-2006) to the first of CVD incidence, death, or September 30, 2016. Cox proportional hazards regression was used to model associations between these T cell subsets and the risk for incident CVD while adjusting for demographics and other CVD risk factors. The median participant age at baseline was 51.6 years. Most were male (94%) and of Black race (69.1%). There were 344 incident CVD events (219 in PWH) during follow-up (median 9.8 years). In PWH, higher proportions (per SD increment) of T helper type 17 cells (adjusted HR: 1.19; 95% CI: 1.08-1.31), T effector memory cells re-expressing CD45RA (adjusted HR: 1.19; 95% CI: 1.07-1.34), and CD28null cells (adjusted HR: 1.18; 95% CI: 1.03-1.34) were significantly associated with an increased risk for incident CVD. Among those without HIV infection, no T cell subsets were significantly associated with CVD. Among PWH, T helper type 17 cells, senescent cells, and CD4+ T effector memory cells re-expressing CD45RA were significantly associated with incident CVD that was not explained by CVD risk factors.