Lung function and cardiovascular disease: a two-sample Mendelian randomisation study.

Area of Science:

• Genetics
• Epidemiology
• Cardiology

Background:

• Observational studies link reduced lung function to increased coronary artery disease (CAD) and ischemic stroke risk.
• This association persists independently of shared risk factors like smoking.
• Causal links between lung function and cardiovascular disease (CVD) require robust investigation.

Purpose of the Study:

• To determine if impaired lung function causally increases the risk of cardiovascular disease.
• To differentiate the causal roles of specific lung function measures (FVC, FEV1) in CVD.
• To address potential biases in previous observational findings.

Main Methods:

• Employed Mendelian randomization (MR) using genetic variants as instrumental variables.
• Utilized two-sample MR in preliminary analysis.
• Applied multivariable MR in the main analysis, conditioning for height, BMI, and smoking to avoid collider bias.

Main Results:

• Strong evidence indicates reduced forced vital capacity (FVC) causally increases coronary artery disease risk (OR 1.32).
• Reduced forced expiratory volume in 1s (FEV1) shows no significant causal association with CAD after adjusting for covariates.
• Weak evidence suggests reduced lung function may increase ischemic stroke risk.

Conclusions:

• Reduced FVC is independently and causally linked to coronary artery disease.
• FVC may be a valuable marker for cardiovascular risk assessment and a potential therapeutic target.
• FEV1 and airflow obstruction do not appear to causally increase CVD events; prior associations may be due to confounding or collider bias.