Global Burden of HIV-Related CVD Has Tripled Over Two Decades

People with HIV are more than twice as likely to develop cardiovascular disease than those without the virus, according to the results of a new review and meta-analysis.

CVD attributable to HIV has more than doubled globally over the past two decades, from 0.36% in 1990 to 0.92% in 2015, while disability-adjusted life-years (DALY), a measure of the number of healthy time lost, tripled in this same period.

“Although the global incidence for HIV has stabilized, the provision and widespread distribution of combined antiretroviral therapy has dramatically improved survival with the prevalence of HIV steadily increasing over the last two decades,” lead researcher Anoop Shah, MD (University of Edinburgh, Scotland), and colleagues write in their paper published online recently in Circulation. “Indeed, most deaths now arise from noncommunicable illnesses, especially heart disease,” they point out.

While the calculated risk of CVD for HIV patients has been estimated in previous studies, the latest analysis estimates this risk on a global scale, said Matthew Feinstein, MD (Northwestern Feinberg School of Medicine, Chicago, IL), who commented on the study for TCTMD. “It’s potentially valuable for people not only practicing in the US and in Europe but in also low and middle-income countries,” he said.

While the exact mechanism behind the higher risk of CVD for people with HIV is not known, the consensus is that it is related to chronic inflammation related to the virus, Feinstein said. Even when the virus is not present in the bloodstream, it can remain in a patient’s tissues and lymph nodes, he explained, adding, “You still have this big systemic response, where [the body] is trying to fight off this infection because it still knows an infection is there.”

Previously HIV medications were thought to contribute to the development of CVD by affecting cholesterol. This may have been the case for older drugs, but with newer therapies, the contribution “to heart disease has really become muted,” Feinstein said.

Data on Nearly 800,000 People With HIV

The authors searched five databases–EMBASE, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, and Web of Science–for longitudinal studies of CVD in individuals infected with HIV. They ultimately selected 80 studies, spanning from the mid-90s to late 2016, to determine the rate and risk of developing CVD in HIV populations.  

They analyzed 793,635 individuals with HIV, with a total follow-up of 3.5 million person-years.

The incidence rate of cardiovascular disease in patients with HIV was 61.8 per 10,000 person-years, which is on par with other risk factors for CVD like diabetes, the authors say. Patients with HIV were more than twice as likely as HIV-negative patients to develop CVD (RR 2.16; 95% CI 1.68-2.77). When broken out by event, risk also was increased for any type of CVD (RR 2.36; 95% CI 1.50-3.70), for MI (RR 1.79;95% CI 1.54-2.08), and for stroke (RR 2.56; 95% CI 1.43-4.61).

Additionally, the study also identified a 2.5-fold increase in CVD attributable to HIV over the last 25 years. DALYs during this same type period also increased, from 0.74 million in 1990 to 2.57 million in 2015. Sub-Saharan Africa had the highest attributable rates of CVD, as well as the highest number of DALYs.

“Cardiovascular disease now accounts for over 10% of all morbidity and mortality in sub-Saharan Africa, with rates that are comparable to high income regions,” Shah and colleagues write. “Consequently, the sub-Saharan region account for half of all disability-adjusted life years attributable to HIV.”

Other burdened areas included Russia and Pacific Asia. 

The Extent of the Problem

While Feinstein believes that these types of studies are “essential” to better understanding the scope of cardiovascular disease, he said more research is needed to understand how the disease develops in HIV patients. Atherosclerosis has been widely studied in relation to HIV, but other areas of heart disease need to be explored.

“We understand the plaque part of [heart attacks] for HIV, but I don’t think we understand the clotting part as well,” he said. Heart failure is an additional avenue to explore, Feinstein suggested. “We know that it is substantially more common in patients with HIV, but we don’t have a great sense of why.”

Higher-risk geographic areas also merit closer attention, according to the investigators. “The pooled risk ratios used to calculate the population attributable fraction and the subsequent cardiovascular burden were primarily obtained from developed nations, but were applied to all regions,” Shah et al state. “This approach is ubiquitous in these types of analysis and highlights the paucity of data from these regions.”

Regardless of these limitations, this study contributes to the understanding of the extent of heart disease in HIV populations globally and is a step toward improving care in the future, Feinstein said.

“As we understand the scope a little bit better, we can also start delving into some of the mechanisms of why people with HIV have higher rates of heart disease,” he said. “From there, we can start to better target preventive efforts and therapies so that people with HIV don’t get heart disease as much, and when they do have heart disease, it doesn’t become associated with as much morbidity and mortality.”