Even Young Adults With HIV at Risk of Low- and Preserved-EF Heart Failure

Marcia Frellick

April 10, 2017

NASHVILLE, TN — Infection with HIV puts adults at higher risk of both heart failure with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) compared with those not infected, suggestions an analysis based on a large US veterans cohort[1].

Antiretroviral therapies (ART) have increased life-spans for people living with HIV, and heart failure has become a prominent complication, but not much is solidly known about mechanisms and other characteristics of heart failure in this population, explain the study's authors, led by Dr Matthew S Freiberg (Vanderbilt University, Nashville, TN) in their report published April 5, 2017 in JAMA Cardiology. For example, whether it tends to be HFrEF or HFpEF could have a big influence on management decisions.

Until this research, Freiberg told heartwire from Medscape, "we haven't had a study large enough to have enough events to look at these different classes."

He and his colleagues analyzed 98,015 people included in the Veterans Aging Cohort Study who did not have cardiovascular disease at baseline. The cohort, in which participants were enrolled in 2003 and followed for 9 years, matched HIV-infected and uninfected vets by age, race/ethnicity, sex, and study site.

They found that, compared with veterans not infected, those with HIV had a 21% higher risk for HFpEF (LVEF at least 50%), a 37% increased risk for borderline HFpEF (LVEF 40%–49%), and a 61% higher risk for HFrEF (LVEF <40%).

Veterans with HIV who were younger than 40 years at the start of the study had more than three times the risk of reduced EF than their uninfected counterparts (hazard ratio [HR] 3.59, 95% CI 1.95–6.58).

That finding was particularly striking, Freiberg told heartwire . "We expect heart failure to occur later in life, not in their 40s. Classically, you think heart failure is due to chronic disease—hypertension for a long time, diabetes a long time, maybe coronary heart disease. But obviously younger people wouldn't have decades of those risk factors."

Dr Priscilla Hsue (San Francisco General Hospital and Trauma Center, CA), who directs her center's HIV cardiology clinic, told heartwire she also found that result surprising. "That was even in the setting of taking out all confounders such as alcohol use, race, and hypertension," noted Hsue, who isn't connected to the current study.

In another noteworthy finding, CD4 counts <200 cells/mm3, vs 500 cells/mm3 or greater, were associated with both kinds of heart failure, suggesting "that duration of HIV infection and, by extension, chronic inflammation, T-cell activation, and loss of adaptive immunity likely all have important roles" in the mechanisms behind the two HF phenotypes, the group writes.

The findings led the researchers to ask, "Is there something about the immune system more generally that is contributing to that heart failure?" Freiberg said. If that's the case, implications go far beyond people with HIV. "Everyone has an immune system."

The data also have messages for providers primarily treating HIV and for cardiologists. For those treating HIV, these results suggest looking for signs of heart failure as well, particularly HFrEF among the young, Freiberg said.

"There's a huge demographic of HIV-infected people who are young," he notes. "As we care for them, we want this to be in the back of our minds."

And for cardiologists: "If unclear heart failure comes along, at least let the thought of HIV cross your mind," he said.

Hsue said that previously, it had been controversial whether people with HIV had higher risk for cardiovascular disease, but "this study adds to the growing body of literature that, whether it's acute myocardial infarction or heart failure or sudden cardiac death, HIV patients have higher risk for cardiovascular disease. That's even in the setting of treated and suppressed HIV disease."

In a related editorial[2], Drs Gerald S Bloomfield and G Michael Felker (Duke University, Durham, NC) say the study answers some key questions about HIV-associated cardiovascular disease.

"First, the results challenge the notion that HFrEF has become an uncommon type of HF among [people living with HIV] in the ART era in a high-income-country setting," they write, adding that the evidence also indicates young and old are at risk.

Bloomfield and Felker also write that more focus on the combination of HIV and reduced ejection fraction in the aging HIV population is critical, particularly because, by 2020, more than half of all people with HIV will be older than 50. Efforts should include heart-failure screening and treatment.

They further observe that the study also provides further evidence that restoring immune-system function reduces risk of heart failure. "Thus, while we await empirical evidence, it is reasonable to initiate therapies early in the disease course to mitigate HF and total cardiovascular disease risk as some have suggested."

Still unanswered, note Bloomfield and Felker, is how HIV and its treatment affect heart-failure risk; nevertheless, it showed the risk in this study was independent of MI and high blood pressure, which are the two leading causes in the general population.

Research has shown consistently that even HIV patients with well-treated disease have higher levels of inflammatory markers and T-cell activation, Hsue adds.

"It's interesting that those higher levels, independently, are very strongly predictive of mortality in cardiovascular disease. So there's been a huge emphasis in the field about the best way to lower those inflammatory markers with the thought that you could delay or prevent cardiovascular disease," she said.

Also unanswered is what link ART has to heart failure, the editorialists and Freiberg et al write. In the age of personalized medicine, and since people with HIV will be using these drugs for decades, this research raises new questions about tailoring ART more specifically to patients.

"If there are a number of different drugs to choose from and you may have hypertension or diabetes in addition to HIV that predisposes you to heart failure, is there an optimal regimen we could give that would suppress the virus and minimize any heart-failure risk?" asked Freiberg.

Hsue said there's no question that ART saves lives of people with HIV over the long term, but she also called for more research in this area, especially into the regimens that will be the least cardiotoxic. "There are very few or no studies looking at optimal treatment for heart failure in the setting of HIV and identifying individuals at risk."

Freiberg reported receiving grants from the National Institutes of Health during the conduct of the study. Disclosures for the coauthors are listed in the paper. The editorialists have no relevant financial relationships.

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