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Original research
Impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bidirectional Mendelian randomisation study
  1. Shiu Lun Au Yeung1,
  2. Maria Carolina Borges2,3,
  3. Debbie A Lawlor2,3,4,
  4. C Mary Schooling1,5
  1. 1School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Adminstrative Region, China
  2. 2MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
  3. 3Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  4. 4National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK
  5. 5School of Public Health and Health Policy, City University of New York, New York, New York, USA
  1. Correspondence to Dr Shiu Lun Au Yeung, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; ayslryan{at}hku.hk

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 randomisation 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 s (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. Bidirectional Mendelian randomisation was used to assess reverse causation.

Results FEV1 and FVC were inversely associated with CAD (OR per SD increase, 0.72 (95% 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 (95% CI 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 (eg, OR for 1SD FEV10.95 (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.

  • not applicable

Data availability statement

Data are available in a public, open access repository. All data used to generate the results can be found in the URLs given in the acknowledgement, online supplemental tables and references.

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Data availability statement

Data are available in a public, open access repository. All data used to generate the results can be found in the URLs given in the acknowledgement, online supplemental tables and references.

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Footnotes

  • Contributors SLAY designed the study, wrote the analysis plan and interpreted the results. SLAY undertook analyses with feedback from MCB, DAL and CMS. SLAY wrote the first draft of the manuscript with critical feedback and revisions from MCB, DAL and CMS. All authors gave final approval of the version to be published. SLAY had primary responsibility for final content.

  • Funding MCB is supported by MRC Skills Development Fellowship (MR/P014054/1). MCB and DAL’s contribution to this study is supported by the British Heart Foundation (AA/18/7/34219) and MCB and DAL work in a Unit receives funding from the University of Bristol and UK Medical Research Council (MRC) (MC_UU_00011/6).

  • Competing interests DAL receives support from several national and international government and charitable research funders, as well as from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. All other authors declared they have no conflict of interest, financial or otherwise.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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