Evaluation of a bidirectional causal association between cardiovascular diseases and pneumonia: a Mendelian randomization study

Abstract Aims Observational evidence suggests a bidirectional relationship between cardiovascular diseases (CVDs) and pneumonia. However, the causality between CVDs and pneumonia remains undetermined. Therefore, in this study, we aim to investigate the bidirectional causality between CVDs and pneumonia using a Mendelian randomization (MR) analysis. Methods and results A global genetic correlation analysis and a bidirectional two-sample MR analysis were performed to infer the genetic correlation and causality between CVDs and pneumonia by using genome-wide association study (GWAS) summary data from a GWAS meta-analysis study and the FinnGen or UK Biobank consortium. Post hoc power calculation was conducted to assess the power for detecting the causality. The linkage disequilibrium score regression analysis suggested a significant positive genetic correlation between CVDs and pneumonia. In the MR analysis, it was found that only genetically predicted ischaemic stroke was causally associated with any pneumonia [odds ratio (OR): 1.119, 95% confidence interval (CI): 1.031–1.393], bacterial pneumonia (OR: 1.251, 95% CI: 1.032–1.516), and pneumococcal pneumonia (OR: 1.308, 95% CI: 1.093–1.565), but the causality was attenuated to non-significance after adjusting for deep venous thrombosis. However, the causal effects of pneumonia on CVDs were not detected. Post hoc power calculations supported a strong power (>80%) to detect the causality. Conclusion Ischaemic stroke is causally associated with an increased risk of pneumonia, but there is no evidence for the causal effect of pneumonia on CVDs. Our findings have important implications, as they provide further support for thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischaemic stroke.