The Casual Relationship between Asthma-related Pneumonia and Heart Failure -- a Bidirectional Two-sample Mendelian Randomization Study

Abstract Background: Observational studies have suggested a higher risk of heart failure in individuals with asthma-related pneumonia. However, there is currently no conclusive evidence establishing a causal relationship between the two or a clear mechanism explaining this association. Methods: We performed a thorough bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal connection between Asthma-related pneumonia and Heart failure. Our study employed five MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. To ensure the reliability of our findings, we conducted sensitivity analyses using different models and testing methods to evaluate the potential effects of heterogeneity and pleiotropy on the outcomes. Our results were consistently robust through these rigorous evaluations. Results: According to the results of IVW analysis, there is a causal relationship between Asthma-related pneumonia and Heart failure risk (OR=1.113, 95%CI: 1.027~1.206, P=0.009). On the other hand, osteoporosis was not found to have a causal effect on PBC risk based on IVW analysis (OR=1.018, 95%CI: 0.780~1.328, P=0.893). The IVs used in all MR analyses showed no heterogeneity or horizontal pleiotropy. Moreover, the leave-one-out analysis revealed that no single SNP disproportionately influenced the results, further confirming the credibility of the bidirectional MR findings. Conclusion: Through this study, it has been established that there is a causal relationship between pneumonia related to Asthma and the risk of heart failure. However, no definitive causal link has been found from heart failure to Asthma-related pneumonia. These insightful findings provide guidance for effectively managing the health of Asthma-related pneumonia with heart failure.