Evidence for a Causal Relationship between Heart Failure and Cerebral Infarction: A Bidirectional Two-Sample Mendelian Randomization Study

Previous studies have shown a potential correlation between heart failure (HF) and cerebral infarction (CI), but its genetic basis is still unclear. This study aim to explore the genetic correlation and potential causal relationships between HF and CI. To analyse the risk relationship between heart failure and cerebral infarction by two-sample bidirectional Mendelian randomization (MR) method using human genome-wide association data analysis (GWAS). Pooled data extracted from GWAS were analyzed to explore the correlation between HF and CI risk in a European population using a two-sample bidirectional MR method. Single nucleotide polymorphisms (SNPs) strongly associated with HF but not with CI were selected as genetic instrumental variables and analyzed using inverse variance weighted (IVW) analysis, weighted median analysis, simple mode, weighted mode and MR-Egger regression to investigate the causal relationship between HF and CI risk. Simultaneously, the stability and accuracy of the results were evaluated through horizontal pleiotropy, heterogeneity testing and exclusion sensitivity testing. IVW analysis showed a causal relationship between the two diseases, with HF being a risk factor for CI (OR = 1.0062, 95% CI 1.0000–1.0125, P = 0.0000), and there was no horizontal pleiotropy (Egger interval = –3.21E-04, P = 0.179) and heterogeneity (P = 0.5613, P = 0.4618). Other statistical methods, such as sensitivity analysis, did not find genetic pleiotropy biasing the results. In contrast, reverse MR results showed no significant causal relationship between CI and HF (OR = 1.89, 95% CI = 0.02–2.84, P = 0.788), and CI was not a risk factor for the development of HF. In a European population, HF may have a unidirectional causal association with CI, but no direct effect independent of HF on CI.