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COVID-19 is associated with the risk of cardiovascular disease death: A two-sample Mendelian randomization study
Jia-Peng Miao1, Xiao-Yu Gu2, Rui-Zheng Shi1
1Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Insights
Infections from Coronavirus disease 2019 (COVID-19) increase the risk of death from cardiovascular disease. This study found that both COVID-19 susceptibility and hospitalization causally link to cardiovascular disease mortality.
Area of Science:
- Cardiovascular Epidemiology
- Infectious Disease Epidemiology
- Genetic Epidemiology
Background:
- The long-term cardiovascular implications of Coronavirus disease 2019 (COVID-19) remain a significant public health concern.
- Understanding the causal relationship between COVID-19 and cardiovascular disease (CVD) outcomes is crucial for risk stratification and prevention.
Purpose of the Study:
- To investigate the potential causal effects of COVID-19 susceptibility and hospitalization on the risk of death from cardiovascular disease.
- To employ robust genetic epidemiological methods to establish causality.
Main Methods:
- Utilized two-sample Mendelian randomization (MR) analysis with summary statistics from large genome-wide association studies (GWAS).
- Included data from over 2.5 million participants for COVID-19 susceptibility, hospitalization, and CVD death.
- Performed sensitivity analyses including MR-Egger regression, heterogeneity tests, and Leave-one-out analyses to ensure result validity.
Main Results:
- COVID-19 susceptibility was found to be a causal factor for cardiovascular disease death (β = 2.188 × 10⁻³, P = 0.002).
- COVID-19 hospitalization also demonstrated a causal link to cardiovascular disease death (β = 8.626 × 10⁻⁴, P = 0.010).
- Sensitivity and reverse MR analyses confirmed the absence of significant heterogeneity, horizontal pleiotropy, or reverse causality.
Conclusions:
- Bidirectional MR analysis provides strong evidence for a causal relationship between COVID-19 (both susceptibility and hospitalization) and an increased risk of cardiovascular disease death.
- These findings underscore the importance of managing cardiovascular risk in individuals affected by COVID-19.
Objective:
This study aimed to estimate the causal effects of Coronavirus disease 2019 susceptibility and hospitalization on cardiovascular disease death using two-sample Mendelian randomization analysis.
Methods:
We used statistics from a genome-wide association study. A total of 2,568,698 participants were assessed in this study, including 1,299,010 in Coronavirus disease 2019 susceptibility databases, 908,494 in Coronavirus disease 2019 hospitalization database, and 361,194 in a cardiovascular disease death database. We performed two-sample Mendelian randomization analysis using the inverse variance weighted method. As sensitivity analysis techniques, Mendelian randomization-Egger regression, heterogeneity analyses, and Leave-one-out analysis were employed. Reverse Mendelian randomization analysis was used to detect reverse causality. Statistical significance was defined as P < 0.05.
Results:
Coronavirus disease 2019 susceptibility may be a causal factor for cardiovascular disease death (β = 2.188 × 10-3, P = 0.002), which involves five common single nucleotide polymorphisms. Similarly, Coronavirus disease 2019 hospitalization may also be a causal factor for cardiovascular disease death (β = 8.626 × 10-4, P = 0.010), which involves nine common single nucleotide polymorphisms. Furthermore, sensitivity and reverse Mendelian randomization analysis suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between Coronavirus disease 2019 and cardiovascular disease death.
Conclusion:
Our bidirectional Mendelian randomization analysis showed a causal relationship between Coronavirus disease 2019 susceptibility and hospitalization associated with an increased risk of cardiovascular disease death.
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