Cardiovascular health and risk of hospitalization with COVID-19: A Mendelian Randomization study

BACKGROUND: Susceptibility to and severity of COVID-19 is associated with risk factors for and presence of cardiovascular disease. METHODS: We performed a 2-sample Mendelian randomization to determine whether blood pressure (BP), body mass index (BMI), presence of type 2 diabetes (T2DM) and coronary artery disease (CAD) are causally related to presentation with severe COVID-19. Variant-exposure instrumental variable associations were determined from most recently published genome-wide association and meta-analysis studies (GWAS) with publicly available summary-level GWAS data. Variant-outcome associations were obtained from a recent GWAS meta-analysis of laboratory confirmed diagnosis of COVID-19 with severity determined according to need for hospitalization/death. We also examined reverse causality using exposure as diagnosis of severe COVID-19 causing cardiovascular disease. RESULTS: We found no evidence for a causal association of cardiovascular risk factors/disease with severe COVID-19 (compared to population controls), nor evidence of reverse causality. Causal odds ratios (OR, by inverse variance weighted regression) for BP (OR for COVID-19 diagnosis 1.00 [95% confidence interval (CI): 0.99–1.01, P = 0.604] per genetically predicted increase in BP) and T2DM (OR for COVID-19 diagnosis to that of genetically predicted T2DM 1.02 [95% CI: 0.9–1.05, P = 0.927], in particular, were close to unity with relatively narrow confidence intervals. CONCLUSION: The association between cardiovascular risk factors/disease with that of hospitalization with COVID-19 reported in observational studies could be due to residual confounding by socioeconomic factors and /or those that influence the indication for hospital admission.