Clinical Question

Is the risk of cardiovascular events increased following COVID-19 infection?

Bottom Line

In this analysis, researchers found a large increase in cardiovascular events in the 12 months following COVID-19 infection, with the greatest risk in those with more severe disease. Although the risk for cardiovascular events is lower in patients with COVID-19 who were not hospitalized, there is a large impact at a population level. There are about 26,000 additional cardiovascular events, including 13,000 major events, per 1 million people with COVID-19 who were not hospitalized. (Level of Evidence = 2b)

Synopsis

This was a retrospective cohort study that identified 5,637,647 veterans who were enrolled in the U.S. Veterans Health Administration (VHA) system in 2019 who did not have a documented positive test result for the SARS-CoV-2 virus, as well as 153,760 veterans who were alive 30 days after a positive test result for the SARS-CoV-2 virus. The distribution of entry dates was adjusted to maintain the comparability of groups. The authors also identified a historic cohort of VHA patients cared for during the two years before the pandemic. The mean age of the cohorts was 61 to 63 years, approximately 20% were Black, and 90% were men. The authors balanced COVID-19 positive and COVID-19 negative groups using propensity scores and did an adjusted analysis. They used a positive outcome control (fatigue) to confirm that they found an association that they expected, and several negative outcome controls (e.g., diagnosis of melanoma in situ, hypertrichosis, lymphoma) to confirm that they did not find an unexpected association. Results for the historic and contemporary controls were similar. The positive and negative outcome controls results were as expected. The likelihood of a patient with COVID-19 experiencing every cardiovascular condition was significantly increased, with hazard ratios for most between 1.5 and 2.5. The risk was increased much more for patients hospitalized with COVID-19, especially those who had been cared for in the intensive care unit (ICU). There would be approximately five additional diagnoses of heart failure in 1,000 nonhospitalized patients, 45 in 1,000 hospitalized patients, and 78 in 1,000 ICU patients. For cerebrovascular disease, the corresponding excess burdens per 1,000 patients are three events for nonhospitalized, 20 for hospitalized, and 31 for ICU patients.

Hazard ratios were somewhat higher among people without preexisting cardiovascular disease, and were consistent by age, race, and sex. The excess burdens of the composite of all-cause mortality, myocardial infarction, and stroke were 13 for nonhospitalized, 51 for hospitalized, and 138 for ICU patients per 1,000 people. For any cardiovascular event, excess burdens were 26 for nonhospitalized, 161 for hospitalized, and 312 for ICU patients.

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Reference: Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.