Risk Manifests Much Earlier in Those Patients

By Annette M. Boyle

WEST HAVEN, CT — Antiretroviral therapy has extended the lives of veterans with human immunodeficiency virus (HIV) by decades, but a new threat could cut back their longevity.

A study published recently in JAMA Cardiology found that veterans with HIV had a 40% increase in heart failure of all types. Those patients had a 61% elevated risk of heart failure with reduced ejection fraction and a 21% increase in heart failure with preserved ejection fraction compared to veterans without HIV infection.1

Veterans with HIV were also found to have a 21% higher risk of borderline heart failure with preserved ejection fraction than other veterans.

During the study, 2,636 heart failure events occurred over a median follow-up period of 7.1 years, with HIV-diagnosed veterans experiencing 941 of those events. Heart failure with reduced ejection fraction accounted for 40% of all events.

“Not only are we seeing a higher rate of heart failure among this group, we are seeing it present decades earlier than expected,” explained lead author Matthew Frieberg, MD, associate professor of Cardiovascular Medicine at Vanderbilt University in Nashville, TN.

The study is touted as the first to show an increased risk of heart failure associated with HIV in the recent antiretroviral therapy (ART) era of HIV. It challenges the assumption that heart failure with reduced ejection fraction had faded as a problem for people living with HIV in high-income countries where ART is available, according to an accompanying editorial.

Still, the authors said they were not surprised to find the increased risk. “Heart failure, like other organ system failures, is often the result of prolonged injury, such as occurs with chronic HIV infection,” pointed out co-author Amy Justice, MD, PhD, lead investigator of the Veterans Aging Cohort Study (VACS) and professor at the Yale School of Public Health in New Haven, CT.

The study used data from VACS, which enrolled 98,015 veterans after April 1, 2003, and followed them through September 30, 2012. Just less than one-third of participants (32.2%) had HIV. Of those, about three-quarters were taking antiretroviral therapy (ART). None of the participants had cardiovascular disease at baseline.

The higher risk for heart failure remained consistent, even when the researchers excluded veterans who had hypertension, had ever smoked or had substance abuse disorders. The findings echoed clinical results for cardiovascular disease more generally.

“Even after adjustment for established risk factors, HIV patients have an increased risk for cardiovascular disease,” Justice said. Veterans in the study who had HIV were less likely to have typical risk factors for heart failure including hypertension, diabetes, hypercholesterolemia and obesity than their uninfected peers.

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Some Good News

The study had good news, however, for many of those on ART. Veterans with CD4 cell counts of less than 200 cells/mm or viral loads higher than 500 copies/ml had greater risk for heart failure than veterans who had less severe disease. Both higher CD4 counts and lower viral load generally correlate with ART.

The authors of an accompanying editorial, Gerald Bloomfield, MD, MHS, and Michael Felker, MD, both of Duke University, Durham, NC, advocated taking steps to boost immune system function and increase CD4 cell counts. They also recommended initiating “therapies early in the disease course to mitigate heart failure and total cardiovascular disease risk.”

Justice took a more nuanced approach. “Overall, ART decreases risk by lowering the burden of the virus,” she told U.S. Medicine, but whether more intervention in this population is a good idea across the board is less clear.

“This is a complicated question because people aging with HIV infection also have more polypharmacy. Ideally, we need to personalize management by identifying those at substantial risk of cardiovascular disease so that we can treat those at risk and avoid unnecessary treatments in those at low to no risk,” she said.

While individuals with HIV infection have higher risk of heart failure than those without the infection, within the affected group, the risk differs significantly based on several factors. The authors noted that “the association between HIV infection and types of heart failure varies by age, race/ethnicity, HIV-specific biomarkers, and receipt of antiretroviral therapy.”

Veterans with HIV who were younger than 40 years of age when the study started, for instance, had a particularly elevated risk of heart failure with reduced ejection fraction—nearly  3.6 times the risk of uninfected young veterans. The authors noted that the risk of this type of heart failure “can manifest decades earlier than would be expected in a typical uninfected population.”

Learning more about which individuals are at risk for which type of heart failure requires further research, as the mechanisms, appropriate therapies and typical outcomes differ between the three subtypes.

They encouraged adoption of a strategy that includes the risk of heart failure in developing treatment plans for individuals with HIV. “We want providers to think about heart failure in this population. It’s imperative that they understand that the risk is there and that we begin to develop guidelines for prevention and management for this high-risk population,” Frieberg said.

  1. Freiberg MS, Chang CH, Skanderson M, Patterson OV, et. al. Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study. JAMA Cardiol. 2017 May 1;2(5):536-546. doi: 10.1001/jamacardio.2017.0264. PubMed PMID: 28384660.