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Cardiovascular health and risk of hospitalization with COVID-19: A Mendelian Randomization study
Marina Cecelja1, Cathryn M Lewis2,3, Ajay M Shah4
1Department of Clinical Pharmacology, King's College London British Heart Foundation Centre, School of Cardiovascular Medicine & Sciences, St Thomas' Hospital, London, UK.
Insights
This study found no causal link between cardiovascular disease risk factors and severe COVID-19. Observational associations may be due to confounding factors, not a direct disease relationship.
Area of Science:
- Genetics
- Epidemiology
- Cardiovascular Disease
Background:
- COVID-19 severity is linked to cardiovascular disease (CVD) risk factors.
- Observational studies suggest an association between CVD and severe COVID-19.
Purpose of the Study:
- To investigate the causal relationship between CVD risk factors and severe COVID-19 using Mendelian randomization.
- To examine potential reverse causality from severe COVID-19 to CVD.
Main Methods:
- A 2-sample Mendelian randomization approach was employed.
- Genetic variants from large genome-wide association studies (GWAS) were used as instrumental variables.
- Severe COVID-19 was defined by hospitalization or death.
Main Results:
- No evidence of a causal association was found between blood pressure, body mass index, type 2 diabetes, or coronary artery disease and severe COVID-19.
- Reverse causality from severe COVID-19 to CVD was also not supported.
- Odds ratios for the associations were close to unity with narrow confidence intervals.
Conclusions:
- The observed association between CVD and severe COVID-19 in observational studies may be attributed to residual confounding.
- Socioeconomic factors or factors influencing hospital admission indications could explain the association.
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.
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