Chaddock, N.J.M., Harden, C.J., Sorensen, L. et al. (10 more authors) (2025) Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis. Annals of the Rheumatic Diseases, 84 (2). pp. 329-340. ISSN 0003-4967
Abstract
Objectives
This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits.
Methods
1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested. A model for cranial ischaemic complications was optimised using an elastic net approach. Positional gene mapping of associated PRS was performed to improve biological understanding.
Results
In a sample of 1946 GCA patients (median age=71, 68.7% female), 17% had cranial ischaemic complications at presentation. In univariable analyses, 10 variables were associated with complications (likelihood-ratio test p≤0.05). In multivariable analysis, the two variables with the strongest effects, with or without PRS in the model, were anticoagulant therapy (adjusted OR (95% CI)=0.21 (0.05 to 0.62), p=4.95×10‾³) and age (adjusted OR (95% CI)=1.60 (0.73 to 3.66), p=2.52×10‾³, for ≥80 years versus <60 years). In sensitivity analyses omitting anticoagulant therapy from multivariable analysis, age and hypertension were associated with cranial ischaemic complications at presentation (hypertension: adjusted OR (95% CI)=1.35 (1.03 to 1.75), p=0.03). Positional gene mapping of an associated transient ischaemic attack PRS identified TEK, CD96 and MROH9 loci.
Conclusion
Age and hypertension were risk factors for cranial ischaemic complications at GCA presentation, but in this dataset, anticoagulation appeared protective. Positional gene mapping suggested a role for immune and coagulation-related pathways in the pathogenesis of complications. Further studies are needed before implementation in clinical practice.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). Published by Elsevier B.V. on behalf of European Alliance of Associations for Rheumatology (EULAR). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | Giant Cell Arteritis, Cardiovascular Disease, Polymorphism, Genetics |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Funding Information: | Funder Grant number NIHR National Inst Health Research Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Jun 2025 09:21 |
Last Modified: | 04 Jun 2025 09:23 |
Published Version: | https://www.sciencedirect.com/science/article/pii/... |
Status: | Published |
Publisher: | BMJ |
Identification Number: | 10.1136/ard-2024-225515 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:227377 |