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Lookup NU author(s): Professor John IsaacsORCiD, Dr Alice Lorenzi, Dr Gary Reynolds, Ross Farley, Helain Hinchcliffe-Hume, Dr Ismael Atchia
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.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.
Author(s): 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, Raashid LH, Martin S, Robinson JI, Morgan A, Mackie S, Wordsworth O, Whitwell I, Brock J, Douglas V, Hettiarachchi C, Bartholomew J, Jarrett S, Smithson G, Green M, Brown PC, Lawson C, Gordon E, Lane S, Francis R, Dasgupta B, Masunda B, Calver J, Patel Y, Thompson C, Gregory L, Levy S, Menon A, Thompson A, Dyche L, Martin M, Li C, Laxminarayan R, Wilcox L, de Guzman R, Isaacs J, Lorenzi A, Reynolds G, Farley R, Hinchcliffe-Hume H, Bejarano V, Hope S, Nandi P, Stockham L, Wilde C, Durrant D, Lloyd M, Ye C-S, Stevens R, Jilani A, Collins D, Pegler S, Rivett A, Price L, McHugh N, Skeoch S, O'Kane D, Kirkwood S, Vadivelu S, Pugmire S, Sultan S, Dooks E, Armstrong L, Sadik H, Nandagudi A, Abioye T, Ramos A, Gumus S, Sofat N, Harrison A, Seward A, Mollan S, Rahan R, Hawkins H, Emsley H, Bhargava A, Fleming V, Hare M, Raj S, George E, Allen N, Hunter K, O'Sullivan E, Bird G, Magliano M, Manzo K, Sanghera B, Hutchinson D, Hammonds F, Sharma P, Cooper R, McLintock G, Al-Saffar ZS, Green M, Elliott K, Neale T, Mallinson J, Lanyon P, Pradere M-J, Jordan N, Htut EP, Mushapaidzi T, Abercrombie D, Wright S, Rowlands J, Mukhtyar C, Kennedy J, Makkuni D, Wilhelmsen E, Kouroupis M, Bhagat S, John L, Hughes R, Walsh M, Buckley M, Mackay K, Camden-Woodley T, Redome J, Pearce K, Marianayagam T, Cruz C, Warner E, Atchia I, Walker C, Black K, Duffy S, Bukhari M, Fothergill L, Jefferey R, Toomey J, Dillon CR, Pothecary C, Green L, Toms T, Maher L, Davis D, Sayan A, Thankachen M, Abusalameh M, Record J, Khan A, Stafford S, Hussein A, Williams C, Fletcher A, Johson L, Burnett R, Moots R, Frankland H, Dale J, Moar K, Hollas C, Parker B, Ridings D, Eapen S, John S, Robson J, Guthrie LB, Fyfe R, Tait M, Marks J, Gunter E, Hernandez R, Bhat S, Johnston P, Khurshid M, Barclay C, Kapur D, Jeffrey H, Hughes A, Slack L, Thomas E, Royon A, Hall A, King J, Nyathi S, Morris V, Castelino M, Hawkins E, Tomson L, Singh A, Nunag A, O'Connor S, Rushby N, Hewitson N, O'Sunmboye K, Lewszuk A, Boyles L, Perry M, Williams E, Graver C, Defever E, Kamanth S, Kay D, Ogor J, Winter L, Horton S, Welch G, Hollinshead K, Peters J, Labao J, Dmello A, Dawson J, Graham D, De Lord D, Deery J, Hazelton T
Publication type: Article
Publication status: Published
Journal: Annals of the Rheumatic Diseases
Year: 2024
Pages: epub ahead of print
Online publication date: 03/10/2024
Acceptance date: 28/08/2024
Date deposited: 28/10/2024
ISSN (print): 0003-4967
ISSN (electronic): 1468-2060
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/ard-2024-225515
DOI: 10.1136/ard-2024-225515
Data Access Statement: Data are available on reasonable request. Data access requests should be directed to the corresponding author. UK Biobank data may be accessed by completing an application at https://www.ukbiobank.ac.uk/. Generated PRS is available on request.
PubMed id: 39362697
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