Bidirectional Causality Between Cardiovascular Diseases and Pneumonia via Mendelian Randomization
Overview
This study used Mendelian randomization to investigate the causal relationship between cardiovascular diseases (CVDs) and pneumonia. Results showed a significant causal effect of ischaemic stroke on increased pneumonia risk, mediated by deep venous thrombosis, but no evidence supported pneumonia causing CVDs.
Background
Cardiovascular diseases remain the leading cause of mortality worldwide, with increasing evidence linking them to pneumonia, which worsens outcomes and mortality. Observational studies suggest a bidirectional association, but causality remains unclear due to confounding factors. Mendelian randomization offers a genetic approach to infer causality, avoiding reverse causation bias. This study aimed to clarify the causal links between CVDs and pneumonia using genome-wide association study data.
Data Highlights
Condition
Odds Ratio (OR)
95% Confidence Interval (CI)
Association
Ischaemic stroke → Any pneumonia
1.119
1.031–1.393
Significant causal association
Ischaemic stroke → Bacterial pneumonia
1.251
1.032–1.516
Significant causal association
Ischaemic stroke → Pneumococcal pneumonia
1.308
1.093–1.565
Significant causal association
After adjusting for deep venous thrombosis
Not significant
–
Association attenuated
Pneumonia → CVDs
Not detected
–
No causal effect found
Key Findings
Linkage disequilibrium score regression revealed a significant positive genetic correlation between CVDs and pneumonia.
Mendelian randomization showed ischaemic stroke causally increases risk of various pneumonia types.
The causal effect of ischaemic stroke on pneumonia was attenuated after adjusting for deep venous thrombosis, indicating mediation.
No evidence was found for pneumonia causing cardiovascular diseases in the reverse MR analysis.
Post hoc power calculations confirmed strong statistical power (>80%) to detect causal effects.
Clinical Implications
These findings highlight the importance of thrombosis risk screening in patients with ischaemic stroke to potentially reduce pneumonia incidence. Clinicians should be aware of the increased pneumonia risk following stroke and consider preventive strategies. The lack of causal effect from pneumonia to CVDs suggests focusing interventions on stroke-related mechanisms rather than pneumonia as a direct cause of CVD.
Conclusion
Ischaemic stroke is causally associated with an increased risk of pneumonia, mediated by deep venous thrombosis, while pneumonia does not causally increase cardiovascular disease risk. This supports targeted thrombosis screening to mitigate pneumonia risk post-stroke.
References
Investigation of the Bidirectional Causal Link Between Cardiovascular Diseases and Pneumonia Through Mendelian Randomization Analysis
