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

Yeshen Zhang; Haobin Liu; Yining Dai; Fei Ye; Wenzhi Luo; Shan Tu; Weikun Chen; Siyu Kong; Yu He; Ning Tan; Zhihui Zhang; Pengcheng He; Yuanhui Liu

doi:10.1093/eurjpc/zwae060

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

Eur J Prev Cardiol. 2024 Feb 13:zwae060. doi: 10.1093/eurjpc/zwae060. Online ahead of print.

Authors

Yeshen Zhang^{1

2}, Haobin Liu¹, Yining Dai¹, Fei Ye², Wenzhi Luo², Shan Tu², Weikun Chen¹, Siyu Kong¹, Yu He¹, Ning Tan¹, Zhihui Zhang², Pengcheng He¹, Yuanhui Liu¹

Affiliations

¹ Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
² Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.

PMID: 38349335
DOI: 10.1093/eurjpc/zwae060

Abstract

Aims: Observational evidence suggests a bidirectional relationship between cardiovascular diseases (CVDs) and pneumonia. However, the causality between CVDs and pneumonia remains undetermined. Thus, we aimed to investigate the bidirectional causality between CVDs and pneumonia using Mendelian randomization (MR) analysis.

Methods: Global genetic correlation analysis and 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 GWAS meta-analysis study, FinnGen or UK Biobank consortium. Post-hoc power calculation was conducted to assess the power for detecting the causality.

Results: The linkage disequilibrium score regression analysis suggested a positive significant genetic correlation between CVDs and pneumonia. In the MR analysis, only genetically predicted ischemic 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 strong power (more than 80%) to detect the causality.

Conclusions: Ischemic 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 the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.

Keywords: Mendelian randomization; cardiovascular diseases; pneumonia.

Plain language summary

This Mendelian randomization analysis aimed to investigate the bidirectional causality between cardiovascular diseases and pneumonia. Our findings support the causal association of ischemic stroke on pneumonia, but indicate no evidence for the causal effects of pneumonia on cardiovascular diseases. The causal association of ischemic stroke on pneumonia was revealed to rely on deep venous thrombosis, which provided further support for the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.