Giant study shows striking rise in long-term heart and vessel disease

BY MEREDITH WADMAN

From very early in the pandemic, it was clear that SARS-CoV-2 can damage the heart and blood vessels while people are acutely ill. Patients developed clots, heart inflammation, arrythmias, and heart failure.

Now, the first large study to assess cardiovascular outcomes 1 year after SARS-CoV-2 infection has demonstrated that the virus’ impact is often lasting. In an analysis of more than 11 million U.S. veterans’ health records, researchers found the risk of 20 different heart and vessel maladies was substantially increased in veterans who had COVID-19 1 year earlier, compared with those who didn’t. The risk rose with severity of initial disease and extended to every outcome the team examined, including heart attacks, arrhythmias, strokes, cardiac arrest, and more. Even people who never went to the hospital had more cardiovascular disease than those who were never infected.

The results are “stunning … worse than I expected, for sure,” says Eric Topol, a cardiologist at Scripps Research. “All of these are very serious disorders. … If anybody ever thought that COVID was like the flu this should be one of the most powerful data sets to point out it’s not.” He adds that the new study “may be the most impressive Long Covid paper we have seen to date.”

Others agree the results of the study, published in Nature Medicine on 7 February, are powerful. “In the post-COVID era, COVID might become the highest risk factor for cardiovascular outcomes,” greater than well-documented risks such as smoking and obesity, says Larisa Tereshchenko, a cardiologist and biostatistician at the Cleveland Clinic, who recently conducted a similar, much smaller analysis. She cautions that the new study will need to be replicated, and that it was retrospective, possibly introducing inaccuracies such as incorporating faulty diagnoses from patient records. “It looked back. We have to do prospective studies to calculate accurate estimates.”

Nor do researchers know how the virus orchestrates this long-term damage. But they think the cardiovascular risks and the constellation of symptoms collectively known as Long Covid (which include brain fog, fatigue, weakness, and loss of smell) could have common roots.

“This is clearly evidence of long-term heart and vascular damage. Similar things could be happening in the brain and other organs resulting in symptoms characteristic of Long Covid, including brain fog,” says senior author Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis and chief of research at the VA St Louis Health Care system.

The researchers drew on the largest set of electronic health records in the United States, at the Department of Veterans Affairs (VA). They analyzed data from nearly 154,000 people who contracted COVID-19 between March 2020 and January 2021, and who survived at least 30 days after becoming infected. They also identified two control groups: 5.6 million people who sought VA care during the pandemic but were not diagnosed with COVID-19, and 5.9 million people who sought VA care in 2017.

One limitation of the study is that the veteran population skews older, white, and male: In all three groups, about 90% of patients were men and 71% to 76% were white. Patients were in their early 60s, on average.

The researchers controlled for the possibility that the people who contracted COVID-19 were already more prone to developing cardiovascular disease. They found that “COVID is an equal opportunity offender,” Al-Aly says. “We found an increased risk of cardiovascular problems in old people and in young people, in people with diabetes and without diabetes, in people with obesity and people without obesity, in people who smoked and who never smoked.”

COVID-19 boosted the risk of all 20 cardiovascular ailments studied, including heart attacks, arrhythmias, strokes, transient ischemic attacks, heart failure, inflammatory heart disease, cardiac arrest, pulmonary embolism, and deep vein thrombosis.

For example, veterans who had had COVID-19 faced a 72% higher risk of heart failure after 12 months than those in a control group who didn’t test positive. That translated to nearly 12 more infected people per 1000 developing heart failure than those in a control group. Overall, the investigators found 45 more infected people per 1000 developed any of the 20 conditions than did uninfected controls.

Because the researchers used statistical tools to try to correct for the scarcity of women and people of color in the study, the results are likely to be relevant for those groups, too, says Elizabeth Ofili, a preventive cardiologist at Morehouse School of Medicine who focuses on disparities in heart disease between men and women. “The correction for gender and race goes a long way,” she says.

Just how the virus causes long-term damage to the heart and blood vessels remains a matter of debate and active research. One possible mechanism is inflammation of the endothelial cells that line the inside of the heart and blood vessels, Al-Aly says. But the researchers also include a laundry list of potential mechanisms, including lingering damage from direct viral invasion of the heart muscle; elevated levels of proinflammatory chemical messengers called cytokines that lead to scarring of the heart; and persistent virus in sites not effectively dealt with by the immune system. “The putative mechanistic pathways are still in the realm of speculation or hypothesis,” Al-Aly says.

The authors say their findings suggest millions of COVID-19 survivors could suffer long-term consequences, straining health systems for years to come. “Governments and health systems around the world should be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a rise in the burden of cardiovascular diseases,” they write in the paper.

Al-Aly adds: “What really worries me is that some of these conditions are chronic conditions that will literally scar people for a lifetime. It’s not like you wake up tomorrow and suddenly no longer have heart failure.”

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