Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection

Background: 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.

Objectives: The aim of this study was to explore the association between peripherally circulating CD4⁺ T cell subsets and incident CVD.

Methods: 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.

Results: 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 CD28^null 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.

Conclusions: 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.