Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk scores, indicating individual's hereditary risk, were linearly associated with increased risks of post-COVID-19 atrial fibrillation (adjusted HR 1.52 [95% CI 1.44 to 1.60] per standard deviation increase), coronary artery disease (1.57 [1.46 to 1.69]), venous thromboembolism (1.33 [1.18 to 1.50]), and ischaemic stroke (1.27 [1.05 to 1.55]). These genetic associations are robust across genders, key clinical subgroups, and during Omicron waves. However, a prior composite healthier lifestyle was consistently associated with a reduction in all outcomes. Our findings highlight that host genetics and lifestyle independently affect the occurrence of CVE complications in the acute infection phrase, which can guide tailored management of COVID-19 patients and inform population lifestyle interventions to offset the elevated cardiovascular burden post-pandemic.
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