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

Natalie J M Chaddock; Charlotte J Harden; Louise Sorensen; Hannah R Mathieson; Michal Zulcinski; Catherine A Lawson; Eoin O'Sullivan; Susan P Mollan; Javier Martin; Sarah L Mackie; Mark M Iles; Ann W Morgan; UK GCA Consortium

doi:10.1136/ard-2024-225515

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

Ann Rheum Dis. 2024 Oct 3:ard-2024-225515. doi: 10.1136/ard-2024-225515. Online ahead of print.

Authors

Natalie J M Chaddock¹, Charlotte J Harden^{1

2}, Louise Sorensen^{1

3}, Hannah R Mathieson^{1

3}, Michal Zulcinski^{1

3}, Catherine A Lawson⁴, Eoin O'Sullivan⁵, Susan P Mollan^{6

7}, Javier Martin⁸, Sarah L Mackie^{1

3}, Mark M Iles^{1

3}, Ann W Morgan^{9

2

3}; UK GCA Consortium

Collaborators

UK GCA Consortium:
Ann W Morgan, Sarah L Mackie, Louise Sorensen, Lubna Haroon Raashid, Steve Martin, James I Robinson

Affiliations

¹ School of Medicine and Leeds Institute for Data Analytics, University of Leeds, Leeds, UK.
² NIHR Leeds Medicines and In Vitro Diagnostics Co-operative, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
³ NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
⁴ Harrogate District Hospital, Harrogate, UK.
⁵ Ophthalmology, King's College Hospital NHS, London, UK.
⁶ Ophthalmology, University Hospitals Birmingham, Birmingham, UK.
⁷ Neurometabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
⁸ Institute of Parasitology and Biomedicine, López-Neyra, IPBLN, CSIC, Granada, Spain.
⁹ School of Medicine and Leeds Institute for Data Analytics, University of Leeds, Leeds, UK a.w.morgan@leeds.ac.uk.

PMID: 39362697
DOI: 10.1136/ard-2024-225515

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; Giant Cell Arteritis; Polymorphism, Genetic.