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COVID-19 Vaccination and Risk of Post-COVID-19 Cardiovascular Disease: A Population-Based Cohort and Target Trial
Binyam Tariku Seboka1,2, Dianna J Magliano3,4, Thomas H Marwick1,2,5
1Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia.
Background:
Whether COVID-19 vaccination is associated with lower long-term cardiovascular risk after SARS-CoV-2 infection and how much infection prevention mediates this association remain unclear.
Objective:
To evaluate associations of vaccination, including its timing relative to SARS-CoV-2 infection, with post-COVID-19 cardiovascular disease (CVD), and quantify the contribution of infection prevention.
Methods:
This statewide population-based cohort study used linked administrative health data for 2,391,456 adults in Victoria, Australia (2019-2025). Associations of pre- or post-infection vaccination with major adverse cardiovascular events (MACE; primary outcome), stroke, heart failure, acute myocardial infarction (AMI), acute coronary syndrome (ACS), atrial fibrillation (AF), and venous thromboembolism (VTE) were evaluated using time-varying Cox proportional hazards regression, causal mediation analysis, and target trial emulation.
Results:
Vaccination was associated with lower hazards of MACE and all secondary outcomes. Estimated absolute risk reductions for MACE were 0.21% with pre-infection vaccination and 0.24% with post-infection vaccination. Three or more vaccine doses were associated with progressively lower hazards across cardiovascular outcomes. Mediation analysis suggested that approximately 68% of the estimated association between vaccination and lower post-COVID cardiovascular risk was not explained by prevention of SARS-CoV-2 infection.
Conclusion:
Vaccination before or after SARS-CoV-2 infection was associated with lower hazards of post-COVID-19 cardiovascular outcomes, with stronger observed associations at higher dose numbers. Most of the estimated association was not explained by infection prevention alone. These findings support COVID-19 vaccination as an important component of strategies to reduce the burden of post-COVID-19 CVD while highlighting the need for further studies to clarify the mechanisms underlying these associations.
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