Among people with HIV infection, three types of CD4+ T helper cells are associated with incident cardiovascular disease (CVD) that are not explained by CVD risk factors, according to a study whose first author is from Vanderbilt University Medical Center.
The study, “Circulating T Cells and Cardiovascular Risk in People With and Without HIV Infection,” was recently published in the Journal of the American College of Cardiology. It is one of the largest human studies of its type to report the association, said first author Suman Kundu, DSc, research assistant professor in the Division of Cardiovascular Medicine.
People with HIV infection have immune system activation that results in a lower CD4+ cell count, which is associated with CVD. Kundu said the paper sheds further light on the underlying mechanism of why HIV-infected people have a greater risk of CVD, potentially improving the ability to predict CVD risk.
“The aim of the study was getting more granular data within the CD4+ compartment on how alteration in specific adaptive immune cells is associated with CVD risk using a large cohort of people with and without HIV,” he said.
The study included 1,860 people without CVD at baseline, 1,270 of whom have HIV infection as part of the Veteran Aging Cohort Study, which is a prospective, observational study. The cohort’s median age was 51.6 years, and most were men (94%) and of Black race (69.1%).
Participants were followed from baseline until they developed CVD, died, or were censored in September 2016. With a median follow up of 9.8 years, 344 CVD events were observed. CVD was defined as acute myocardial infarction, unstable angina, coronary artery revascularization (percutaneous coronary intervention or coronary artery bypass graft), ischemic stroke and heart failure.
The study examined several specific T helper cell types that earlier animal and smaller size human studies suggest might be associated with CVD: Th1, Th17, Treg, TEMRA and CD28 (senescent). The study team used Cox proportional hazards regression models to examine the associations with adjusting for demographics, CVD risk factors and other measures of comorbidity.
Among participants with HIV infection, Th17, senescent, and TEMRA CD4+ T cells were significantly associated with future CVD events. “This association persisted even after adjustment for CVD risk factors, substance use, and biomarkers of inflammation, altered coagulation, and monocyte activation,” the paper states.
Moreover, people without HIV infection saw no increased risk of CVD with the T helper cells.
Kundu said the research suggests that future studies should drill down even further into the role of antigen specificity in the T cells, to develop further data that may be used for improving CVD risk prediction.
The paper’s senior author was Margaret Doyle, PhD, of the University of Vermont. Other Vanderbilt authors of the paper were Matthew Freiberg, MD, John Koethe, MD, Meredith Duncan, PhD, Hilary Tindle, MD, and Joshua Beckman, MD.
