Mechanism Behind HIV Link to CVD Still Uncertain

September 13, 2022

Although it is known that individuals living with HIV infection have an increased risk for cardiovascular disease, the underlying pathology behind this observation remains unclear, the authors of a new analysis say.

"Over the last few decades people with HIV are living longer. The majority of deaths in this group are now due to cardiovascular causes, and individuals with HIV are at a higher risk of cardiovascular events than the general population. But we don't know what the typical cardiovascular pathology is in those with HIV," senior author of the new analysis, Anoop Shah, MD, London School of Hygiene and Tropical Medicine, United Kingdom, commented to | Medscape Cardiology.

To look into this issue, Shah and colleagues conducted a systematic review of data from advanced cardiovascular imaging studies evaluating CT coronary angiography, PET, and cardiac MRI in people living with HIV compared with uninfected individuals.

The review was published online in JAMA on September 13.

The authors identified 45 studies including 5218 people living with HIV and 2414 uninfected individuals.

Results showed that the prevalence of moderate to severe coronary disease among those with HIV ranged from 0% to 52% compared with 0% to 27% for those without HIV, with prevalence ratios ranging from 0.33 to 5.19.

Several studies showed that myocardial fibrosis was common in HIV infection, with prevalence of myocardial fibrosis among those with HIV ranging from 5% to 84% compared with 0% to 68% for those without HIV, suggesting that myocardial fibrosis is likely to be a key pathogenic mechanism in the cardiovascular morbidity and mortality observed in people living with HIV, the researchers say.

However, the underlying etiology of HIV-associated cardiac pathology and whether its association observed with HIV remains true in regions of high endemicity still remains unclear, they add.

Shah noted that the studies analyzed had used different imaging technologies to look at coronary artery plaque, the heart muscle and vascular inflammation.

"In all these different cases there was a wide variation in results, with some studies showing an association between HIV and these cardiovascular pathologies and others not showing any association," he reported.

He pointed out that one of the main problems is that the vast majority of the studies of cardiovascular imaging in individuals with HIV were conducted in North America and Europe whereas the vast majority of individuals living with HIV are in Africa.

"People with HIV in Europe and North America are very different to those in Africa. The available studies of cardiac imaging involved mainly men aged between 50 and 60, whereas the global HIV population is made up of mostly women who are typically aged at least a decade younger," Shah said.  

"Cardiac studies in individuals with HIV have so far involved people with other cardiovascular risk factors such as smoking, high cholesterol and diabetes. The occurrence of these other vascular risk factors is high in the Western population, particularly in older males who have mainly been included in these cardiac studies. But the global population with HIV would probably have fewer other cardiovascular risk factors," he said.

"Overall, we know that cardiovascular disease is a big problem in individuals with HIV but the majority of studies of cardiovascular imaging in people with HIV have been done in a misrepresented population, and the results are too variable to draw any specific conclusions," he added.

In addition, most of the studies they analyzed only used single modality technology, Shah noted. "A multimodal approach to imaging looking at all aspects of heart disease would be more useful. Going forward, we need to do studies in the right population with the right technology."

Noting that there is also a link between other viral infections including COVID-19 and cardiovascular disease, Shah said that there was still little understanding on the mechanisms involved.

"While links have been shown between both acute and chronic viral infections and cardiovascular disease in population and epidemiological studies, the mechanistic studies are lacking. The common pathologic mechanism is likely to be inflammation, but we don't really understand how exactly this affects the heart and blood vessels."

Given the data from these studies are so variable, it is difficult to make any clinical recommendations, Shah said.

"Our analysis highlights the large knowledge gap in the link between HIV and cardiovascular disease. While we know individuals with HIV are at higher cardiovascular risk, we don't know what exactly to look for," he said. "Current guidelines advise watching out for and treating vascular risk factors in the HIV population, but these guidelines are aimed at the Western population. How they relate to the African HIV population, we are not sure."

In an accompanying editorial, Matthew J. Feinstein, MD, Feinberg School of Medicine, Northwestern University, Chicago, says although associations of HIV with cardiovascular imaging markers varied considerably by individual study in the current analysis, some unifying findings were apparent.

These included a higher prevalence of myocardial fibrosis and higher vascular inflammatory measurements on PET imaging in individuals with HIV than in controls.

He says a "somewhat surprising finding" was that there was not a consistently higher prevalence of coronary atherosclerosis for people living with HIV vs controls in all studies, but he suggests that this might have been owed to heterogeneous study populations and comparison groups.

"Overall, the authors' thorough review clearly highlights the limitations of current data and demonstrates how little can be definitively concluded regarding effects of general HIV serostatus on subclinical cardiovascular disease."

Feinstein notes that a more relevant next set of questions may not relate to how HIV is associated with cardiovascular disease but rather which specific factors among people living with HIV predispose some to cardiovascular disease and protect others against cardiovascular disease.

"Future studies recognizing the fundamental immunologic heterogeneity among

people living with HIV and probing this factor have the opportunity to advance important clinical and scientific knowledge on precise immunopathogenic factors underlying cardiovascular disease in specific HIV populations," he concludes.

JAMA. Published online September 13, 2022. Full text; editorial

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