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Published on: May 30, 2013
Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection
Suman Kundu1, Matthew S Freiberg2, Russell P Tracy3
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Insights
In people with HIV, specific CD4+ T cell subsets like T helper 17 cells are linked to higher cardiovascular disease (CVD) risk. These associations were not found in individuals without HIV.
Area of Science:
- Immunology
- Cardiology
- Infectious Diseases
Background:
- Lower CD4+ T cell counts in people with HIV (PWH) are linked to increased cardiovascular disease (CVD) risk.
- The specific CD4+ T cell subsets contributing to this elevated CVD risk remain unclear.
Purpose of the Study:
- To investigate the association between specific CD4+ T cell subsets in peripheral circulation and the risk of developing incident CVD.
- To determine if these associations differ between individuals with and without HIV infection.
Main Methods:
- Analysis of data from the prospective, observational Veterans Aging Cohort Study (VACS) including 1,860 participants (1,270 PWH).
- Quantification of T cell subsets using flow cytometry in baseline samples.
- Incident CVD events were tracked using ICD codes, with follow-up until September 30, 2016. Cox proportional hazards regression was employed for analysis.
Main Results:
- Higher proportions of T helper type 17 cells, T effector memory cells re-expressing CD45RA, and CD28null cells were significantly associated with increased incident CVD risk in PWH.
- These associations in PWH remained significant after adjusting for demographics and other CVD risk factors.
- No significant associations between T cell subsets and CVD risk were observed in participants without HIV infection.
Conclusions:
- Specific CD4+ T cell subsets, including T helper type 17 cells and CD4+ T effector memory cells re-expressing CD45RA, are associated with incident CVD in people with HIV.
- These associations are independent of traditional CVD risk factors.
- The findings highlight potential immune-based mechanisms contributing to CVD in PWH.
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 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.
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.
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