Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis
Chaddock, Natalie J M Harden, Charlotte J Sorensen, Louise Mathieson, Hannah R Zulcinski, Michal Lawson, Catherine A O'Sullivan, Eoin Mollan, Susan P Martin, Javier Mackie, Sarah L
Chaddock, Natalie J M
Harden, Charlotte J
Sorensen, Louise
Mathieson, Hannah R
Zulcinski, Michal
Lawson, Catherine A
O'Sullivan, Eoin
Mollan, Susan P
Martin, Javier
Mackie, Sarah L
Abstract
OObjectives: 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.
MIDER Authors
Affiliations
University of Leeds; Leeds Teaching Hospitals NHS Trust; Harrogate and District NHS Foundation Trust; King’s College Hospitals NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Institute of Parasitology and Biomedicine Granada
Date
2025-01-02
Type
Article
Collections
Citation
Chaddock NJM, Harden CJ, Sorensen L, Mathieson HR, Zulcinski M, Lawson CA, O'Sullivan E, Mollan SP, Martin J, Mackie SL, Iles MM, Morgan AW; UK GCA Consortium. Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis. Ann Rheum Dis. 2025 Feb;84(2):329-340. doi: 10.1136/ard-2024-225515. Epub 2025 Jan 2.