Asthma and incident coronary heart disease: an observational and Mendelian randomisation study
Carlos A. Valencia-Hernández, Fabiola Del Greco M, Varun Sundaram, Laura Portas, Cosetta Minelli, Chloe I. Bloom
European Respiratory Journal 2023; DOI: 10.1183/13993003.01788-2023
Abstract
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a “triangulation approach”, where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.
First, we conducted an observational study using U.K. medical records to match asthma patients, by age, sex and GP practice, 1:1 to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian Randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium, and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium. Using 64 asthma SNPs, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.
In our observational study (N=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR=1.06, 95%CI=1.01–1.13), after accounting for healthcare behaviour, we found no association (model 2: HR=0.99, 95% CI=0.94–1.05). Asthma severity did not modify the association, but sex did (females: HR=1.11, 95%CI=1.01–1.21; males: HR=0.91, 95%CI=0.84–0.98). Our MR study (N=589 875) found no association between asthma and CHD (OR=1.01; 95%CI=0.98–1.04) and no modification by sex.
Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: CVH, FDG, LP, VS, CM have no COI to disclose. CIB reports awards and grants from National Institute for Health and Care Research and Asthma+Lung UK, outside the submitted work.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received September 1, 2023.
- Accepted October 23, 2023.
- Copyright ©The authors 2023.
