Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies

John J McCabe; Cathal Walsh; Sarah Gorey; Katie Harris; Pablo Hervella; Ramon Iglesias-Rey; Christina Jern; Linxin Li; Nobukazu Miyamoto; Joan Montaner; Annie Pedersen; Francisco Purroy; Peter M Rothwell; Catherine Sudlow; Yuji Ueno; Mikel Vicente-Pascual; William Whiteley; Mark Woodward; Peter J Kelly

doi:10.1177/23969873241246489

Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies

Eur Stroke J. 2024 Apr 10:23969873241246489. doi: 10.1177/23969873241246489. Online ahead of print.

Authors

John J McCabe^{1

2

3}, Cathal Walsh^{1

4}, Sarah Gorey^{1

2

3}, Katie Harris⁵, Pablo Hervella⁶, Ramon Iglesias-Rey⁶, Christina Jern^{7

8}, Linxin Li⁹, Nobukazu Miyamoto¹⁰, Joan Montaner^{11

12

13

14}, Annie Pedersen^{7

8}, Francisco Purroy^{15

16}, Peter M Rothwell⁹, Catherine Sudlow^{17

18}, Yuji Ueno¹⁰, Mikel Vicente-Pascual^{15

16}, William Whiteley^{18

19}, Mark Woodward^{5

20}, Peter J Kelly^{1

2

3}

Affiliations

¹ Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland.
² School of Medicine, University College Dublin (UCD), Ireland.
³ Stroke Service, Department of Geriatric Medicine and Neurology, Mater Misericordiae University Hospital, Dublin, Ireland.
⁴ Department of Biostatistics, Trinity College Dublin, Ireland.
⁵ George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
⁶ Neuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neuroscience Research Laboratory, Health Research Institute of Santiago de Compostela, Santiago De Compostela, Spain.
⁷ Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Department of Laboratory Medicine, Gothenburg, Sweden.
⁸ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
⁹ Wolfson Centre for the Prevention of Stroke and Dementia, University of Oxford, Oxford, UK.
¹⁰ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
¹¹ Department of Neurology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
¹² Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Neurology, Seville, Spain.
¹³ Department of Neurology, Virgen Macarena Hospital, Sevilla, Spain.
¹⁴ Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁵ Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, Spain.
¹⁶ Department of Clinical Neurosciences, Institut Reserca Biomèdica Lleida, University of Lleida, Spain.
¹⁷ Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹⁸ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
¹⁹ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
²⁰ George Institute for Global Health, Imperial College London, London, UK.

PMID: 38600679
DOI: 10.1177/23969873241246489

Abstract

Introduction: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear.

Materials and methods: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event.

Results: Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17-1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06-1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03-1.39), but not after adjustment (RR 1.11, 95% CI 0.94-1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16-1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82-1.18) (P_interaction = 0.01). Similar associations were observed for recurrent stroke.

Discussion and conclusion: Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.

Keywords: Fibrinogen; inflammation; prognosis; recurrence; stroke.