Vaccinated Patients Have Lower Acute MI, Stroke Risks After COVID-19

The risks of acute MI or ischemic stroke up to about 4 months after having COVID-19 appear to be lower in patients who have been fully vaccinated against SARS-CoV-2 than in those who have not received any doses of vaccine, according to a research letter published online last week in JAMA.

Both outcomes occurred infrequently 30 to 120 days after a COVID-19 diagnosis, but the risk was lower among those who had previously received two vaccine doses (adjusted HR 0.42; 95% CI 0.29-0.62), lead author Young-Eun Kim, PhD (National Health Insurance Service, Wonju, South Korea), and colleagues report.

Study author Kyungmin Huh, MD (Samsung Medical Center, Seoul, South Korea), drew a parallel between influenza and SARS-CoV-2, noting that the flu has been associated with an increased risk of major acute cardiovascular events that can be mitigated through vaccination.

“COVID-19 also increases the risk of ischemic stroke and acute myocardial infarct,” Huh said in an email. “Vaccines against SARS-CoV-2 have been proven effective in the prevention of COVID-19 and its progression to severe disease. However, it was yet unclear if the COVID-19 vaccines also reduce the risk of ischemic stroke and acute MI after COVID-19. Our study suggests that the COVID-19 vaccines do reduce such risk.”

Korean Nationwide Data

The investigators examined data from the Korean nationwide COVID-19 registry and the Korean National Health Insurance Service database, focusing on 231,037 adults diagnosed with COVID-19 between July 2020 and December 2021; 73% were considered fully vaccinated (two doses of an mRNA vaccine or a viral-vector vaccine) and the rest had not received any doses of COVID-19 vaccine.

A protective effect against COVID-19 and its progression to severe disease is by itself a sufficient reason to get vaccinated. But our findings add an important additional benefit. Kyungmin Huh

Before adjustment, the fully vaccinated were older (median age 57 vs 42) and had more comorbidities, but were less likely to develop severe or critical COVID-19. After inverse probability of treatment weighting was applied to adjust for differences between groups, the differences in age and comorbidities were lessened but the gap in severe/critical COVID-19 widened. The authors acknowledge that the remaining imbalance is a limitation of the study, stating that “the decision to be vaccinated is affected by multiple factors that may also be associated with cardiovascular risk. A robust model was applied to mitigate the effect of such imbalances, but the possibility of unobserved bias remains.”

The primary outcome of the study was a composite of hospitalizations for acute MI or ischemic stroke occurring 31 to 120 days after the COVID-19 diagnosis, with cases observed in the first 30 days excluded because of the challenge of distinguishing between cardiovascular events that were complications of COVID-19 versus a result of acute-phase treatments.

During the period of interest, the rate of acute MI or ischemic stroke (per 1,000,000 person-days) was 6.18 in the unvaccinated and 5.49 in the fully vaccinated, a significant difference. The lower risk associated with vaccination was seen for both acute MI (adjusted HR 0.48; 95% CI 0.25-0.94) and ischemic stroke (adjusted HR 0.40; 95% CI 0.26-0.63) and was consistent across subgroups (though not all of the differences reached statistical significance).

The analysis cannot provide information about potential mechanisms to explain the results, but Huh said “one possible hypothesis is that prior COVID-19 vaccination attenuates systemic inflammation and a hypercoagulable state caused by COVID-19, thus lessening the risk of vascular complications. I believe that further study on the inflammatory cytokines and coagulation profiles in unvaccinated versus vaccinated COVID-19 patients will follow.”

James de Lemos, MD (UT Southwestern Medical Center, Dallas, TX), who was not involved in the study, said the results make sense. “It fits the context of what we’re learning about the longer-term heart complications of COVID, and this adds the piece that by preventing [severe cases of] COVID, vaccination may prevent these later-term heart complications,” he commented.

These findings also play into the discussion around vaccine safety even though they don’t directly address that issue, said de Lemos, who serves as co-chair of the steering committee for the American Heart Association’s COVID-19 CVD Registry. If the vaccines lessen the risks of acute MI and ischemic stroke by preventing severe cases of COVID-19, then that’s additional information to consider when weighing the risks and benefits, he indicated.

“People focus on only the question of myocarditis, which is a rare but real potential side effect of the vaccine, but that has to be balanced against all of the protective effects on the respiratory complications of COVID, on long COVID, and now here on intermediate and longer term cardiovascular complications,” he said.

Overall, de Lemos said, “this provides additional support for vaccination providing meaningful clinical benefits, and suggests that those benefits extend to some protection of cardiac complications from COVID even in the recovery period.”

Huh agreed: “A protective effect against COVID-19 and its progression to severe disease is by itself a sufficient reason to get vaccinated. But our findings add an important additional benefit of vaccination, especially for people with cardiovascular risk factors.”