Understanding the bidirectional relationship between chronic respiratory disease and cardiovascular disease using genetic evidence.

BACKGROUND

Chronic respiratory diseases (CRDs) and cardiovascular diseases (CVDs) are leading global health burdens. Despite being common, CRD and CVD comorbidity is often underestimated due to overlapping symptoms and risk factors. Consequently, their relationship remains unclear.

AIMS AND

OBJECTIVES

To determine the bidirectional genetic relationship between CRD and CVD and explore smoking and inflammation as potentially shared joint risk factors.

METHODS

We conducted bidirectional Mendelian randomisation (MR) to explore CRD-CVD relationships. Summary statistics from genome-wide association studies were retrieved for chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), myocardial infarction (MI), heart failure, atrial fibrillation (AF) and ischaemic stroke (IS). We performed additional analysis including univariable MR for smoking, multivariable MR adjusting for smoking and cis-MR to investigate the role of inflammatory markers.

RESULTS

Our MR analysis found limited genetic evidence of relationships between CRD and CVD, and vice versa. However, a nominally significant genetic association was observed between asthma and an increased risk of AF (OR inverse-variance weighted (ORIVW) 1.036, 95% CI 1.003 to 1.070), remaining weakly significant after adjusting for smoking (ORIVW 1.040, 95% CI 1.008 to 1.074). Genetically predicted lifetime smoking strongly increased all CRD and CVD risk. Additionally, genetically proxied IL6R concentration associated with increased asthma risk and decreased CAD, MI, AF and IS risk, while IL1RN decreased COPD risk but increased CAD and MI risk.

CONCLUSIONS

While we found limited genetic evidence linking CRD and CVD, smoking and inflammatory markers commonly affect both. These findings highlight the complexity of CRD-CVD comorbidities, whose pathophysiology likely does not involve direct causation of each other.