Circulating T cells tied to CVD risk in people with HIV infection

Subsets of peripheral circulating CD4 T cell among people with HIV infection (PWH) are predictive of incident cardiovascular disease (CVD), including heart failure and atherosclerotic CVD, reveals a study.

Such association remains significant even after adjusting for CVD risk factors, substance use, and biomarkers of inflammation, altered coagulation, and monocyte activation. However, it remains unclear whether this relationship exists among those without HIV infection.

“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,” the researchers said. [J Am Coll Cardiol 2022;80:1633-1644]

A total of 1,860 participants (median age 51.6 years, 94 percent male, 69.1 percent Black) without prevalent CVD from the Veterans Aging Cohort Study were included in the analysis.

The researchers quantified T cell subsets in baseline samples using flow cytometry. They identified incident CVD events using International Classification of Diseases-9th Revision and International Classification of Diseases-10th Revision diagnosis and procedure codes.

Participants were followed from baseline (2005‒2006) to the first CVD incidence, death, or until 30 September 2016. Associations between T cell subsets and risk of incident CVD were assessed using Cox proportional hazards regression, adjusting for demographics and other CVD risk factors.

Of the participants, 1,270 were PWH. During follow-up (median 9.8 years), 344 incident CVD events (219 in PWH) were recorded.

Greater proportions of T helper type 17 cells (adjusted HR, 1.19, 95 percent confidence interval, 1.08‒1.31), T effector memory cells re-expressing CD45RA (adjusted HR, 1.19, 95 percent CI, 1.07‒1.34), and CD28^null cells (adjusted HR, 1.18, 95 percent CI, 1.03‒1.34) in PWH significantly correlated with a higher risk for incident CVD.

On the other hand, no T cell subsets significantly correlated with CVD among those without HIV.

Risk prediction

“Our findings add support to the hypothesis that accelerated senescence, as captured by T_EMRA and CD28^null CD4 cells, is associated with increased risk for CVD,” the researchers said. “Furthermore, our finding that this association is independent of CVD risk factors suggests that these T cell subsets may aid in CVD risk prediction.”

Prediction tools for coronary heart disease often underperform among PWH even in the presence of HIV-specific factors such as total CD4 count. The addition of proinflammatory T cell subsets to improve risk prediction remains to be tested, according to the researchers.

Earlier studies showed that a reduction in total CD4⁺ cell count among PWH may contribute to a higher risk of incident acute myocardial infarction, ischaemic stroke, and heart failure. [JAMA Intern Med 2013;173:614-622; JAMA Cardiol 2017;2:536-546; J Am Heart Assoc 2021;10:e017637]

Other studies also reported the association of peripheral circulating T cell subsets with prevalent CVD and subclinical atherosclerosis. [PLoS ONE 2014;9:e86920; Front Immunol 2019;10:2795; Arterioscler Thromb Vasc Biol 2015;35:258-264]

“Future studies should further explore the role of adaptive immunity, including T cell antigen specificity and chemokine-chemokine receptor interactions, as possible mechanisms for the excess risk for CVD among PWH and whether inclusion of these T cell subsets improves CVD risk prediction,” the researchers said.