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

Shiu Lun Ryan Au Yeung, Maria Carolina Borges, Debbie A Lawlor, C Mary Schooling

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Introduction: Observational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be confounded. We conducted a two 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: 260) and forced vital capacity (FVC: 320) from publicly available UK Biobank summary statistics (n=421,986) and applied to GWAS summary statistics for coronary artery disease (CAD) (n=184,305), stroke (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, with various sensitivity analyses. Bi-directional Mendelian randomization was used to assess reverse causation.

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)), and some stroke subtypes. FEV1 and FVC were inversely associated with type 2 diabetes and systolic blood pressure. Sensitivity analyses produced similar findings although the association with CAD was attenuated after adjusting for height (e.g. OR for 1SD FEV1 0.95 (0.75 to 1.19), but not for stroke or type 2 diabetes. There was no strong evidence for reverse causation.

Conclusion: Higher lung function likely protect against CAD and stroke.
Original languageEnglish
JournalThorax
Publication statusAccepted/In press - Apr 2021

Keywords

  • atrial fibrillation
  • coronary artery disease
  • heart failure
  • lung function
  • Mendelian randomization
  • stroke

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