People infected with the COVID-19 virus in 2020 may have double the risk for future heart attacks, strokes or premature death from any cause up to three years later – even if they never showed signs of severe illness, according to new research. The risk may be considerably higher in people hospitalized for COVID-19 in the first year of the pandemic.

The findings suggest that being hospitalized for COVID-19 in 2020 was a "coronary artery disease risk equivalent," conferring a higher risk for future heart attacks, strokes or death in people without a history of cardiovascular disease than the risk for people with a history who didn't have COVID. The continued increased risk was especially pronounced in people with non-O blood types, representing what the study's authors say is one of the first examples of an interaction between genes and a pathogen that increases heart attack and stroke risk in people.

The analysis, which did not include people infected after vaccines were widely available, was published in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology.

"From the get-go, we knew there was an increased risk of cardiovascular events, but we thought it might be just during the acute phase of infection," said the study's co-senior author, Dr. Hooman Allayee, a professor of population and public health sciences at the University of Southern California's Keck School of Medicine in Los Angeles. "Our study shows three years out, people who got COVID during that first wave of infections are at continued increased risk for heart attacks, strokes and dying.

"COVID, despite the vaccines, is still a public health issue," he said. "Not only does COVID infect the lungs and cause long COVID, this thing just loves the vascular system."

Allayee said the new research found that "even for people who just tested positive but did not necessarily develop severe symptoms, the risk for cardiovascular events was twice as high. It appears to do damage that is long-lasting in some individuals, and that's what we are seeing."

Previous studies have shown that the cardiovascular system could be affected in up to 25% of people admitted to the hospital for COVID-19, causing heart attacks, irregular heart rhythms, heart failure, cardiac arrest or strokes.

Research also has found that blood type may play a role in both COVID-19 susceptibility and the risk of developing cardiovascular problems. Prior studies have found that people with type O blood had a lower risk of becoming infected with the virus that causes COVID-19 than those with other blood types, and that people with type A or B have a higher risk for heart disease, heart attacks, blood clots and strokes compared to their type O peers.

In the new study, researchers analyzed data from the UK Biobank – one of the world's largest and most comprehensive health data sources – for 10,005 people who tested positive for the coronavirus or were hospitalized in the U.K. for COVID-19 between Feb. 1 and Dec. 31, 2020. Researchers wanted to know whether the disease – at any stage of severity – was linked to an increased long-term risk for major cardiovascular events and whether blood type played a role.

They tracked the development of heart attacks, strokes and death from any cause for more than 1,000 days, or roughly three years, following infection.

Regardless of disease severity, participants infected with the virus had double the risk for major cardiovascular events over the course of the study as people not infected with the virus. Those hospitalized for COVID-19 faced a nearly fourfold increase in continued risk for major cardiovascular events compared to people who tested negative for COVID-19.

The increased risk for heart attacks and strokes appeared to result from an interaction with the ABO locus – the gene responsible for determining blood type – and was more pronounced in people with A, B and AB blood types compared to people with type O blood, who did not exhibit increased risk for heart attacks or strokes. About 60% of the global population has a non-O blood type.

The study also showed that people hospitalized with COVID-19 with no history of cardiovascular disease were seven times more likely than their healthy, COVID-negative peers to experience major cardiovascular events within three years. If the hospitalized patients had cardiovascular disease, they were 12 times more likely to experience a subsequent heart attack, stroke or death.

While Allayee and his colleagues did not study how COVID-19 increased the risk for cardiovascular events, prior research sheds some light on potential mechanisms, he said.

A 2023 study in Nature Cardiovascular Research found evidence of the virus in the artery walls of people who died of COVID-19. The virus also had triggered an inflammatory response, releasing molecules known to contribute to heart attacks and strokes. The findings suggest the virus increases the risk for heart attacks and strokes by infecting the artery walls and settling into existing plaques, Allayee said.

"The virus infects the heart itself, but it also infiltrates the cells in the artery walls and the cells inside plaque that has built up there," he said. "If we are seeing an increased risk of heart disease and stroke three years later, that infiltration may somehow destabilize the plaque and do damage to the artery wall that makes plaque more likely to rupture."

Because the new findings stem from an observational and not a randomized study, researchers can't say for certain that COVID-19 infections are causing the higher risk, said Dr. Sandeep Das, a professor of medicine in the department of internal medicine's division of cardiology at UT Southwestern Medical Center in Dallas.

"What we can say is that there's an association," said Das, who was not involved in the new study. "But we can't exactly randomize people to have COVID-19 to know for sure."

However, the link between blood type, COVID infection and future cardiovascular event risk lends credence to the theory that COVID-19 may be increasing the chances of having a heart attack or stroke, he said. "That, at least circumstantially, argues there's some biology involved in creating a higher vulnerability. Observational data don't prove causality, but they certainly don't disprove it either."

The study makes an important contribution to researchers' understanding of what happens to people with COVID-19 over time, Das said.

"When COVID first appeared, we were really worried about its acute cardiac effects," he said. "As our management of this infection has gotten better, we're becoming more concerned about the long-term cardiovascular complications. But there isn't a ton of data."

The new findings raise questions about whether and how to treat people with COVID-19 to prevent future cardiovascular events, Allayee said.

"If this is replicated in future studies, cardiologists need to start thinking about what to do for these people," he said. "Diabetes is also a coronary artery disease risk equivalent. If we treat people who have diabetes with medication to prevent heart disease, should we do the same for people who were hospitalized for COVID-19?"

Findings from a subanalysis in the study point to one potential preventive measure that might be considered, Allayee said. Among people hospitalized for COVID-19 with no history of cardiovascular disease, those who took antiplatelet medications, such as aspirin, faced a slightly lower risk for heart attacks and strokes than those who didn't.

"Do we need to start treating these people with aspirin?" he asked.

Daily use of aspirin, even at a low dose, might not be appropriate for everyone, especially if there's no history of heart attack or stroke, according to 2019 guidelines from the AHA and American College of Cardiology for preventing cardiovascular disease. People should consult with their primary care physician before taking low-dose aspirin.

However, there are many preventive measures people can and should take to prevent heart attacks and strokes, whether they've had COVID-19 or not, Das said.

And for those who have, "you can't go back and not have COVID," he said. "Just realize you might be at higher risk than you would otherwise think based on your risk factors. Check the things you can modify. Quit smoking, exercise, eat a healthy diet. Make sure your blood sugar is controlled, and blood pressure is controlled. All those things can reduce your risks."

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American Heart Association News covers heart and brain health. Not all views expressed in this story reflect the official position of the American Heart Association. Copyright is owned or held by the American Heart Association, Inc., and all rights are reserved.