A new study found that hospitalization for COVID-19 conferred a risk of major adverse cardiac events equivalent to that of coronary artery disease. The research also revealed a genetic interaction between COVID-19 and ABO blood type that influenced thrombotic risk.
In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, investigators analyzed data from 10,005 COVID-19 cases and 217,730 controls in the UK Biobank. The investigators used Cox proportional hazards models to assess the association of COVID-19 infections with the risk of incident thrombosis, all-cause mortality, and the composite MACE trait. They adjusted for age, sex, self-reported ethnicity, education, diabetes, asthma, smoking status, lipid-lowering medication use, and antihypertension medication use.
They found that COVID-19 infections at all levels of severity were associated with a significantly higher risk of myocardial infarction (MI), stroke, or all-cause mortality over 1,003 days of follow-up (hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.94–2.25, P < .0005). The association was even more pronounced among cases requiring hospitalization (HR = 3.85, 95% CI = 3.51–4.24, P < .0005).
Notably, patients hospitalized with COVID-19 infections without a history of cardiovascular disease (CVD) had an approximately 20% increased risk of experiencing major adverse cardiac events (MACE) compared with COVID-19–negative patients with CVD (HR = 1.21, 95% CI = 1.08–1.37, P < .005). This finding suggested that hospitalization for COVID-19 infections represented a coronary artery disease (CAD) risk equivalent.
The study also identified a significant genetic interaction between COVID-19 infections and ABO blood type (P interaction = .011). Hospitalization for COVID-19 infections increased the risk of MI and stroke to a greater extent in patients with non-O blood types (HR = 1.65, 95% CI = 1.29–2.09, P = 4.8×10−5) compared with patients with blood type O (HR = 0.96, 95% CI = 0.66–1.39, P = .82).
Sensitivity analyses demonstrated that the risk of MACE in COVID-19 cases was consistently elevated during the first, second, and third year following diagnosis. The effect sizes were comparable between groups, except in men and younger subjects.
The investigators also explored the potential mitigating effect of antiplatelet agents. Among primary prevention patients without known CVD who were hospitalized for COVID-19 infections and not on antiplatelet agents, the thrombotic risk remained elevated (HR = 1.98, 95% CI = 1.39–2.82, P < .0005). However, the risk was not significantly increased among those reporting antiplatelet agent use.
Genetic analyses were performed to investigate potential interactions between COVID-19 infections and genetic determinants of COVID-19 severity, SARS-CoV-2 infection susceptibility, and atherosclerotic CAD. No significant interactions were found with variants at the chromosome 3p21 locus (associated with COVID-19 traits) or the chromosome 9p21 locus (associated with CAD).
The investigators noted several limitations of their study, including the inability to ascertain undiagnosed CVD in patients with severe COVID-19 infections and the lack of specific information on medication use at the time of SARS-CoV-2 infection. They also acknowledged that the number of patients on antiplatelet agents may have limited the power to evaluate the effects of these medications on thrombosis risk.
The study found that development of COVID-19 infections requiring hospitalization was associated with a risk level equivalent to that of coronary artery disease, with a higher risk of thrombosis observed among cases with non-O blood types. The investigators noted that these findings may have implications for cardiovascular risk assessment and prevention strategies in patients hospitalized for COVID-19 infections. They also suggested that the results could open new areas for research into the biological mechanisms underlying cardiovascular outcomes in severe SARS-CoV-2 infection.
Conflict of interest disclosures can be found in the study.