A Clue to Increased Hypertension Risk in People Living with HIV

A Clue to Increased Hypertension Risk in People Living with HIV
Targeting eosinophils may treat, and even prevent, hypertension.

People living with HIV are at an increased risk for cardiovascular disease, including hypertension. New research published in the Journal of the American Heart Association indicates that the immune system may play a role, finding that hypertensive people living with HIV (PLWH) exhibit higher levels of circulating eosinophils compared to normotensive PLWH.

“We discovered a significant association between elevated eosinophils and hypertension that might represent a novel pathway leading to hypertension in HIV-infected adults,” wrote the authors.

The findings suggest that targeting inflammation, particularly the maturation of eosinophils, may be a therapeutic strategy to treat or prevent hypertension in PLWH.

“This was an international collaboration as part of the University of Zambia (UNZA)-Vanderbilt Partnership for HIV-Nutrition-Metabolic Research,” said senior author Annet Kirabo, Ph.D., an assistant professor of medicine at Vanderbilt University Medical Center. Sepiso Masenga, Ph.D., a trainee of the UNZA-Vanderbilt partnership, is first author on the study.

Immune Responses in Hypertension

Kirabo is an expert on the role of inflammation and immune responses in hypertension and the recipient of the 2020 Harry Goldblatt Award for Early Career Investigators from the American Heart Association. The award recognizes a new investigator whose research has significantly contributed to the understanding of hypertension and cardiovascular disease.

Previous discoveries from Kirabo’s research team have provided critical insight into mechanisms by which excess dietary salt influences the immune system to promote hypertension. In addition, her group has revealed that high salt intake is associated with changes in the gut microbiome that contribute to inflammation and high blood pressure.

HIV Infection and Inflammation

In their latest publication, Kirabo and colleagues assessed inflammatory biomarkers in a cohort of 70 PLWH on a long-term single antiretroviral therapy (ART) regimen. The cohort is part of the Adiposity and Immune Activation study led by John Koethe, M.D., an assistant professor of infectious diseases at Vanderbilt.

The analysis revealed that both circulating eosinophils and plasma levels of interleukin-5, a key eosinophil maturation factor, were elevated in hypertensive but not normotensive PLWH.

“Eosinophils are commonly known for their involvement in allergic hypersensitivity reactions and to our knowledge, this is the first study to implicate eosinophils in hypertension,” Kirabo said. Increased macrophage activation as well as cytokine production and signaling were also associated with hypertension in PLWH.

“To our knowledge, this is the first study to implicate eosinophils in hypertension.”

Further analysis of two HIV-negative cohorts, including more than 80,000 people,1 revealed that eosinophil counts were also elevated in hypertensive compared to normotensive people without HIV, but the association was explained by increased BMI.

“The fact that the association in HIV-negative individuals was explained by increased BMI might mean that the underlying inflammation associated with obesity may share the interkeukin 5-eosinophil pathway in that of HIV,” Kirabo explained.

Collaboration Leads to Results

The findings may point to a novel pathway leading to hypertension in PLWH. “Further research is needed to determine the specific contribution of the HIV-positive status versus ART on inflammation and how they may contribute to hypertension and cardiovascular disease,” wrote the authors.

Kirabo emphasized the longstanding collaboration that made this project possible and globally relevant. More than half of the study’s authors are affiliated with universities in Zambia. “The UNZA-Vanderbilt partnership includes a ‘sandwich’ Ph.D. program in which the degree is awarded by the University of Zambia, with courses taken at Vanderbilt, and co-mentorship from both Vanderbilt and UNZA investigators,” Kirabo said. “I have been very fortunate to serve as a mentor of trainees and as a member of the leadership committee for this partnership.”