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. 2022 Oct 25;80(17):1633-1644.
doi: 10.1016/j.jacc.2022.08.756.

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

Suman Kundu  1 , Matthew S Freiberg  2 , Russell P Tracy  3 , Kaku A So-Armah  4 , John R Koethe  2 , Meredith S Duncan  5 , Hilary A Tindle  1 , Joshua A Beckman  1 , Matthew J Feinstein  6 , Wyatt J McDonnell  7 , Amy Justice  8 , Margaret F Doyle  9 ; Veterans Aging Cohort Study
Affiliations

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

Suman Kundu et al. J Am Coll Cardiol. .

Abstract

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.

Keywords: HIV; cardiovascular disease; circulating T cells; peripheral.

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Conflict of interest statement

Funding Support and Author Disclosures This material is based upon work supported by the VA, the Veterans Health Administration, and the Office of Research and Development, National Institute on Alcohol Abuse and Alcoholism (grants U24-AA020794, U01-AA020790, U24-AA022001, and U10 AA013566), and grant R01HL125032. Dr So-Armah’s work on this project was supported by National Institutes of Health grants K01HL134147, R61DA047032, and P30AI042853. The funders had no role in the study design or the collection, analyses, and interpretation of data. The views expressed in this paper are those of the authors and do not necessarily reflect the position or policy of the VA. Dr Beckman is a consultant for AstraZeneca, Bristol Myers Squibb, Amgen, Merck, Sanofi, Antidote Pharmaceutical, and Boehringer Ingelheim; and serves on data and safety monitoring committees for Bayer and Novartis. Dr McDonnell is an employee and shareholder of 10x Genomics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. CD4 Subsets and Incident Cardiovascular Disease, Heart Failure, and Atherosclerotic Cardiovascular Disease
Adjusted Cox proportional hazards model assessing the relationship of baseline T cell subsets and (A) composite cardiovascular disease (CVD) (including heart failure, acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke), (B) incident heart failure, and (C) incident atherosclerotic CVD (including acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke). Adjusted for age, race/ethnicity, cytomegalovirus antibody status, hypertension, diabetes, lipid levels, body mass index, hepatitis C virus status, hemoglobin, smoking status, estimated glomerular filtration rate, history of alcohol abuse, cocaine abuse, interleukin-6, D-dimer, and soluble CD14. HRs are reported per SD increment with 95% CIs, and no corrections for multiple testing were applied.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. CD4 Subsets and Incident Cardiovascular Disease, Heart Failure, and Atherosclerotic Cardiovascular Disease
Adjusted Cox proportional hazards model assessing the relationship of baseline T cell subsets and (A) composite cardiovascular disease (CVD) (including heart failure, acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke), (B) incident heart failure, and (C) incident atherosclerotic CVD (including acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke). Adjusted for age, race/ethnicity, cytomegalovirus antibody status, hypertension, diabetes, lipid levels, body mass index, hepatitis C virus status, hemoglobin, smoking status, estimated glomerular filtration rate, history of alcohol abuse, cocaine abuse, interleukin-6, D-dimer, and soluble CD14. HRs are reported per SD increment with 95% CIs, and no corrections for multiple testing were applied.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. CD4 Subsets and Incident Cardiovascular Disease, Heart Failure, and Atherosclerotic Cardiovascular Disease
Adjusted Cox proportional hazards model assessing the relationship of baseline T cell subsets and (A) composite cardiovascular disease (CVD) (including heart failure, acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke), (B) incident heart failure, and (C) incident atherosclerotic CVD (including acute myocardial infarction, unstable angina, coronary artery revascularization, and ischemic stroke). Adjusted for age, race/ethnicity, cytomegalovirus antibody status, hypertension, diabetes, lipid levels, body mass index, hepatitis C virus status, hemoglobin, smoking status, estimated glomerular filtration rate, history of alcohol abuse, cocaine abuse, interleukin-6, D-dimer, and soluble CD14. HRs are reported per SD increment with 95% CIs, and no corrections for multiple testing were applied.
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