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. 2025 Feb;84(2):329-340.
doi: 10.1136/ard-2024-225515. Epub 2025 Jan 2.

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

Natalie J M Chaddock  1 , Charlotte J Harden  2 , Louise Sorensen  3 , Hannah R Mathieson  3 , Michal Zulcinski  3 , Catherine A Lawson  4 , Eoin O'Sullivan  5 , Susan P Mollan  6 , Javier Martin  7 , Sarah L Mackie  8 , Mark M Iles  3 , Ann W Morgan  9 ; UK GCA Consortium
Collaborators, Affiliations
Free article

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

Natalie J M Chaddock et al. Ann Rheum Dis. 2025 Feb.
Free article

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.

Keywords: Cardiovascular Disease; Genetics; Giant Cell Arteritis; Polymorphism.

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