Identification of an increased lifetime risk of major adverse cardiovascular events in UK Biobank participants with scoliosis

Abstract

Background: Structural changes caused by spinal curvature may impact the organs within the thoracic cage, including the heart. Cardiac abnormalities in idiopathic scoliosis patients are often studied post-corrective surgery or secondary to diseases. To investigate cardiac structure, function, and outcomes in participants with scoliosis, phenotype and imaging data of the UK Biobank (UKB) adult population cohort was analysed. Methods: Hospital episode statistics of 502,324 adults were analysed to identify participants with scoliosis. Summary 2D cardiac phenotypes from 39,559 cardiac magnetic resonance imaging (CMR) scans were analysed alongside a 3D surface-to-surface (S2S) analysis. Results: A total of 4,095 (0.8%, 1 in 120) UKB participants were identified to have all-cause scoliosis. These participants had increased lifetime risk of major adverse cardiac events (MACE) (HR=1.45, P<0.001), driven by heart failure (HR=1.58, P<0.001) and atrial fibrillation (HR=1.54, P<0.001). Increased radial and decreased longitudinal peak diastolic strain rates were identified in participants with scoliosis (+0.29, Padj<0.05; -0.25, Padj<0.05; respectively). Cardiac compression of the top and bottom of the heart and decompression of the sides was observed through S2S analysis. Additionally, associations between scoliosis and older age, female sex, heart failure, valve disease, hypercholesterolemia, hypertension, and decreased enrolment for CMR, were identified. Conclusion: The spinal curvature observed in participants with scoliosis alters the movement of the heart. The association with increased MACE may have clinical implications for whether to undertake surgical correction. This work identifies, in an adult population, evidence for altered cardiac function and increased lifetime risk of MACE in participants with scoliosis. Future genetic analyses would aid to assess causality.

Competing Interest Statement

J.S.W. has consulted for MyoKardia, Inc., Foresite Labs, and Pfizer. D.P.O. has consulted for Bayer. All other authors declare no potential conflict of interest.

Funding Statement

This work was supported by the Wellcome Trust [107469/Z/15/Z; 200990/A/16/Z], Medical Research Council (UK), British Heart Foundation [RG/19/6/34387, RE/18/4/34215], and the NIHR Imperial College Biomedical Research Centre. The views expressed in this work are those of the authors and not necessarily those of the funders.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The UK Biobank (UKB) recruited over 500,000 participants aged 40-69 years across the UK between 2006-2010 (National Research Ethics Service, 11/NW/0382, 21/NW/0157)[13]. This project was conducted under the UK Biobank applications 47602 and 40616. All participants provided written informed consent[14].

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

UK Biobank (https://www.ukbiobank.ac.uk/) population reference datasets are publicly available. All analysis code will be available on GitHub (https://github.com/ImperialCardioGenetics/Scoliosis)

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