The impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bi-directional Mendelian randomization study

The impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bi-directional Mendelian randomization study

Publication date: Jun 02, 2020

Background: Observational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be susceptible to residual confounding. We conducted a 2 sample Mendelian randomization study using summary statistics from genome wide association studies (GWAS) to clarify the role of lung function in CVD and its risk factors, and conversely the role of CVD in lung function. Methods: We obtained genetic instruments for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from publicly available UK Biobank summary statistics (n=421,986). We applied these genetic instruments for FEV1 (260) and FVC (320) to publicly available GWAS summary statistics for coronary artery disease (CAD) (n=184,305), stroke and its subtypes (n=446,696), atrial fibrillation (n=1,030,836), and heart failure (n=977,320) and cardiovascular risk factors. Inverse variance weighting was used to assess the impact of lung function on these outcomes. Sensitivity analyses included MR-Egger, weighted median, MR-PRESSO, and multivariable Mendelian randomization. We also conducted bi-directional Mendelian randomization to assess whether CVD affects lung function. Results: FEV1 and FVC were inversely associated with CAD (odds ratio (OR) per standard deviation (SD) increase, 0.72 (95% confidence interval (CI) 0.63 to 0.82) and 0.70 (95%CI 0.62 to 0.78)), overall stroke (0.87 (95%CI 0.77 to 0.97), 0.90 (0.82 to 1.00)), ischemic stroke (0.87 (95%CI 0.77 to 0.99), 0.90 (95%CI 0.80 to 1.00)), small vessel stroke (0.78, (95%CI 0.61 to 1.00), 0.74 (95%CI 0.61 to 0.92)), and large artery stroke (0.69 (95%CI 0.54 to 0.89), 0.72 (95%CI 0.57 to 0.91)). FEV1 and FVC were inversely associated with type 2 diabetes (0.75 (95%CI 0.62 to 0.90), 0.67 (95%CI 0.58 to 0.79)) and systolic blood pressure. Sensitivity analyses produced similar direction for most outcomes although the magnitude sometimes differed. Adjusting for height attenuated results for CAD (e.g. OR for 1SD FEV1 0.95 (0.76 to 1.20), but this may reflect weak instrument bias. This adjustment did not attenuate effects for stroke or type 2 diabetes. No strong evidence was observed for CVD affecting lung function. Conclusion: Higher lung function likely protect against CAD and stroke.


Concepts Keywords
Alcohol Respiratory physiology
Anthropometric Respiratory therapy
Artery Medicine
Atrial Fibrillation Pulmonology
BMI Genetic epidemiology
Body Mass Branches of biology
Bristol RTT
CAD Cardiovascular diseases
Cardiovascular CI ischemic stroke
Cardiovascular Diseases Coronary artery disease
China Stroke diabetes
Cholesterol CI stroke
Confidence Interval Diseases
Coronary Artery Heart failure
Coronary Artery Disease Small vessel stroke
Diabetes CAD stroke
Diastolic Blood Pressure Trained healthcare staff
FEV1 Pulmonary function testing
Forced Expiratory Volume Mendelian randomization
Forced Vital Capacity Spirometry
Genetic Cardiovascular disease
Genetic Predisposition Genome-wide association study
Genome Genotyping
Glucose CVD
Glycated Hemoglobin CAD
Heart Failure
Hong Kong
Ischemic Stroke
Lung Function
Observational Studies
Odds Ratio
Patrick Manson
Physical Activity
Reverse Causation
Standard Deviation
Summary Statistics
Systolic Blood Pressure


Type Source Name
disease MESH cardiovascular diseases
disease MESH risk factors
disease MESH coronary artery disease
disease MESH stroke
disease MESH atrial fibrillation
disease MESH heart failure
drug DRUGBANK Sulodexide
disease MESH type 2 diabetes
disease MESH lifestyle
disease MESH fasting
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Ethanol
drug DRUGBANK Etoperidone
disease MESH Maids

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