Studies have suggested a higher incidence of acute myocardial infarction (AMI) and ischemic stroke after COVID-19 infection related to an increased risk of thrombosis.
Vaccines against SARS-CoV-2 are effective against COVID-19 and its progression to severe disease . However, it is not clear whether vaccines also prevent secondary complications. We examined the association between vaccination and AMI and ischemic stroke after COVID-19 infection.
Methods
We conducted a retrospective cohort study to compare the incidence of AMI and ischemic stroke after COVID-19 infection between patients who were never vaccinated and those who were fully vaccinated (2 doses of mRNA vaccines or viral vector vaccine) against SARS-CoV-2.
The Korean national COVID-19 registry (on infection and vaccination) and the Korea National Health Insurance Service database were used. COVID-19 reporting is mandatory and Korea has universal healthcare coverage.
We included adults aged 18 years or older who were diagnosed with COVID-19, including asymptomatic infections, between July 2020 and December 2021. Exclusion criteria included (1) outcome events less than 3 months before COVID-19 diagnosis. 19; (2) reinfection; (3) COVID-19 hospitalization for 30 or more days and, among vaccinated patients, (4) single dose of vaccine; and (5) diagnosis of COVID-19 before or within 7 days of the second vaccination. The patients were observed until March 31, 2022.
The primary outcome was a composite of hospitalizations for AMI and ischemic stroke that occurred 31 to 120 days after COVID-19 diagnosis; these were identified by diagnosis codes and relevant images. The first 30 days were excluded due to the difficulty in differentiating cardiovascular events that occur as complications of COVID-19 versus acute phase treatment.
Secondary outcomes included the components of the composite outcome. Inverse probability of treatment weighting (IPTW) was used to control for differences in patient characteristics between the 2 groups with standardized differences used to assess covariate balance.
Logistic regression was performed for IPTW with complete vaccination as the independent variable and age, sex, Charlson Comorbidity Index, hypertension, and insurance type as covariates. A Cox proportional hazards model was constructed with IPTW for the outcome events, with sex, age, comorbidities, previous history of outcome events, and severity of COVID-19 (requirement for supplemental oxygen [severe], nasal cannula high flow or higher) respiratory support [critical] vs no respiratory support needed) as covariates.
The proportionality assumption was tested (zph tests) and was met. SAS Enterprise Guide 7 was used for statistical analysis. A 2-tailed P < .05 was considered significant. This study was approved by the Gil Medical Center institutional review board with a waiver of informed consent.
Results
Of 592,719 patients with COVID-19 during the study period, 231,037 patients were included , of whom 62,727 were never vaccinated and 168,310 were fully vaccinated.
Patients who were fully vaccinated were older and had more comorbidities. In contrast, severe or critical COVID-19 was less common in the fully vaccinated group.
Differences in age and comorbidities were reduced after weighting, while COVID-19 severity became less balanced. The median duration of follow-up starting 30 days after COVID-19 was 90 days in the unvaccinated group and 84 days in the fully vaccinated group.
The composite outcome occurred in 31 unvaccinated patients and 74 fully vaccinated patients , with an incidence of 6.18 versus 5.49 per 1,000,000 person-days.
The adjusted risk was significantly lower in the fully vaccinated group (adjusted hazard ratio [aHR], 0.42; 95% CI, 0.29-0.62).
The adjusted risk was significantly lower in fully vaccinated patients for both AMI (aHR, 0.48; 95% CI, 0.25-0.94) and ischemic stroke (aHR, 0.40; 95% CI). , 0.26-0.63).
A lower risk of outcome events was observed in fully vaccinated patients in all subgroups , although some did not reach statistical significance, including those with severe or critical infection.
Discussion
This study found that full vaccination against COVID-19 was associated with a reduced risk of AMI and ischemic stroke after COVID-19. The findings support vaccination , especially for those with risk factors for cardiovascular disease.
Limitations of the study include that reimbursement diagnosis codes were used to capture outcome events. Although the operational definition in this study has been widely used, some diagnostic inaccuracies may exist. Additionally, there were imbalances in patient characteristics based on vaccination status. The decision to get 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.
