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C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant
John J McCabe1, Cathal Walsh1, Sarah Gorey1
1From the Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (J.J.M., C.W., S.G., P.J.K.), Dublin; School of Medicine (J.J.M., S.G., P.J.K.), University College Dublin (UCD); Stroke Service (J.J.M., S.G.), Department of Geriatric Medicine and Department of Neurology (P.J.K.), Mater Misericordiae University Hospital, Dublin; Health Research Institute and Mathematics Applications Consortium for Science and Industry (MACSI) (C.W.), Department of Mathematics and Statistics, University of Limerick, Ireland; George Institute for Global Health (K.H.), University of New South Wales, Sydney, Australia; Neuroimaging and Biotechnology Laboratory (NOBEL) (P.H., R.I.-R.), Clinical Neuroscience Research Laboratory, Health Research Institute of Santiago de Compostela, Spain; Department of Laboratory Medicine (C.J., A.P.), Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg; Department of Clinical Genetics and Genomics (C.J., A.P.), Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden; Wolfson Centre for the Prevention of Stroke and Dementia (L.L., P.M.R.) and Nuffield Department of Population Health (W.N.W.), University of Oxford, United Kingdom; Department of Neurology (N.M., Y.U.), Juntendo University School of Medicine, Tokyo, Japan; Department of Neurology (J.M.), Hospital Universitari Vall d'Hebron, Barcelona; Institute de Biomedicine of Seville (J.M.), IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Neurology; Virgen Macarena Hospital (J.M.), Neurology, Sevilla; Neurovascular Research Laboratory (J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona; Department of Neurology (F.F.P., M.V.-P.), Hospital Universitari Arnau de Vilanova; Department of Clinical Neurosciences (F.F.P., M.V.-P.), Institut Reserca Biomèdica Lleida, University of Lleida, Spain; Centre for Medical Informatics (C.L.S., W.N.W.), Usher Institute of Population Health Sciences and Informatics; Centre for Clinical Brain Sciences (C.L.S.), University of Edinburgh; and George Institute for Global Health (M.W.), Imperial College London, United Kingdom.
Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) are linked to recurrent vascular events after stroke. This finding aids in selecting patients for anti-inflammatory therapy trials in secondary stroke prevention.
Area of Science:
- Neuroscience
- Cardiovascular Medicine
- Immunology
Background:
- Anti-inflammatory therapies are effective for cardiovascular events but their role in stroke recurrence is unclear.
- Identifying specific inflammatory markers associated with stroke recurrence is crucial for targeted secondary prevention strategies.
- Subtype-specific associations are needed to guide patient selection for clinical trials.
Purpose of the Study:
- To analyze the association between inflammatory markers (hs-CRP, IL-6) and vascular recurrence after ischemic stroke or transient ischemic attack.
- To determine if these associations differ based on stroke mechanism.
- To inform patient selection for randomized controlled trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention.
Main Methods:
- Individual participant data (IPD) from 10 studies (8,420 patients) were analyzed.
- Associations between hs-CRP, IL-6, and recurrent major adverse cardiovascular events (MACE) or recurrent stroke were assessed.
- Analyses were stratified by stroke mechanism and adjusted for vascular risk factors and therapies; study-level meta-analysis was also performed.
Main Results:
- Interleukin-6 (IL-6) was associated with increased risk of recurrent MACE in large artery atherosclerosis (LAA), undetermined (UND), and small vessel occlusion (SVO) stroke.
- IL-6 also showed association with recurrent stroke in LAA, SVO, and UND stroke subtypes.
- High-sensitivity C-reactive protein (hs-CRP) was associated with recurrent MACE in UND stroke only.
Conclusions:
- Inflammatory markers, particularly IL-6, are associated with recurrent vascular events in specific ischemic stroke subtypes (LAA, SVO, UND).
- These findings provide evidence for selecting patients based on inflammatory profiles in future RCTs for anti-inflammatory therapies.
- This research supports personalized approaches to secondary stroke prevention.

