Causal Relationship between Pulmonary Hypertension and Atrial Fibrillation and Flutter:a Two-sample Mendelian Randomization Study

ZHOU Ruiling; ZHANG Qiong; WANG Peili; ZHANG Jie; ZHANG He

doi:10.12102/j.issn.1672-1349.2025.23.002

Abstract：Objective:To investigate causal relationship between pulmonary hypertension and atrial fibrillation/flutter by two-sample Mendelian randomization(MR)analysis.Methods:Two-way two-sample MR analyses were performed using publicly available genome-wide association study(GWAS)pooled datasets with inverse variance weighting(IVW),weighted median,MR-Egger regression,simple mode,and weighted mode,with IVW as the primary method of analysis.MR-Egger regression was used for horizontal multivariate testing.Cochran's Q statistic was used to quantify the heterogeneity of instrumental variables,and sensitivity analysis was performed using the leave-one-out method(LOM).Results:The results of the outcome MR analysis showed that there were causal relationship between pulmonary hypertension and increased risk of atrial fibrillation/flutter(IVW:OR=0.999,P=0.974),however,it was noteworthy that atrial fibrillation/flutter was causally associated with an increased risk of PH in reverse MR(IVW:OR=1.506,P=0.001;weighted median:OR=1.612,P=0.026).In the bidirectional MR analysis of pulmonary arterial hypertension and atrial fibrillation/atrial flutter,there was no horizontal pleiotropy or heterogeneity in the instrumental variables.Sensitivity analysis using the leave-one-out method revealed that the MR analysis results were robust.Conclusion:Although some observational studies have suggested a possible association between pulmonary arterial hypertension and atrial fibrillation/atrial flutter,the results of this MR analysis shows that pulmonary arterial hypertension may affect atrial fibrillation/flutter.However,the reverse MR provides evidence that atrial fibrillation/flutter may influence PH.Therefore,not more research is needed to continue exploring the causal relationship between pulmonary arterial hypertension and atrial fibrillation/flutter.