{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:12:56Z","timestamp":1791061976621,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials. Optimal timing of hsCRP\/IL-6 measurement poststroke is unknown, as early blood levels may be confounded by the inflammatory response to brain infarction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Using individual-participant data from a systematic review, we performed a time-course analysis to investigate the association between hsCRP\/IL-6 and recurrent events stratified by timing of sampling. The prespecified coprimary end points after sample measurement were: (1) recurrent major adverse cardiovascular events (first major coronary event, recurrent stroke, or vascular death) and (2) recurrent stroke (ischemic, hemorrhagic, or unspecified). The poststroke dynamics of IL-6\/hsCRP were analyzed by plotting their median (interquartile interval) concentrations within each tenth of the sampling timeframe. Acute\/postacute phases were defined for each biomarker according to the shape of this relationship.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              There were data for 9798 patients from 11 studies (19\u2005891 person-years follow-up, 10 observational cohorts, and 1 randomized trial). Each marker was measured once. IL-6 was markedly elevated &lt;24 hours poststroke compared with postacute levels (\u226524 hours; 11.6 versus 3.02 pg\/mL;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). HsCRP was elevated for 10 days. IL-6 was associated with recurrent major adverse cardiovascular events in the postacute phase (\u226524 hours; risk ratio, 1.30 [CI, 1.19\u20131.41], per unit log\n              <jats:sub>e<\/jats:sub>\n              IL-6), but not in the acute phase (&lt;24 hours; risk ratio, 1.10 [CI, 0.98\u20131.25];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              =0.03). After adjustment for risk factors\/medication, the association remained for postacute IL-6 when analyzed per log\n              <jats:sub>e<\/jats:sub>\n              unit (risk ratio, 1.16 [CI, 1.05\u20131.66]) and per quarter increase (risk ratio, 1.55 [CI, 1.19\u20132.02]; Q4 versus Q1), but not if measured acutely. Similar findings were observed for recurrent stroke. There was no evidence of time-dependent interaction with hsCRP.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Timing of sample measurement after stroke modifies the association with recurrent major adverse cardiovascular events for IL-6 but not hsCRP. These data inform future randomized controlled trial designs incorporating biomarker-based selection of patients for anti-inflammatory therapies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.047820","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:01:46Z","timestamp":1730365306000},"page":"2825-2834","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data"],"prefix":"10.1161","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-1303","authenticated-orcid":true,"given":"John J.","family":"McCabe","sequence":"first","affiliation":[{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin (J.J.M., C.W., S.G., P.J.K.)."},{"name":"School of Medicine, University College Dublin, Ireland (J.J.M., S.G., P.J.K.)."},{"name":"Stroke Service, Mater Misericordiae University Hospital, Dublin, Ireland (J.J.M., S.G., P.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathal","family":"Walsh","sequence":"additional","affiliation":[{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin (J.J.M., C.W., S.G., P.J.K.)."},{"name":"Department of Biostatistics, Trinity College Dublin, Ireland (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-7969","authenticated-orcid":true,"given":"Sarah","family":"Gorey","sequence":"additional","affiliation":[{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin (J.J.M., C.W., S.G., P.J.K.)."},{"name":"School of Medicine, University College Dublin, Ireland (J.J.M., S.G., P.J.K.)."},{"name":"Stroke Service, Mater Misericordiae University Hospital, Dublin, Ireland (J.J.M., S.G., P.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-2301","authenticated-orcid":true,"given":"Markus","family":"Arnold","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital of Zurich, Switzerland (M.A., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-9780","authenticated-orcid":true,"given":"Gian Marco","family":"DeMarchis","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital Basel, Switzerland (G.M.D., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2444-2869","authenticated-orcid":true,"given":"Katie","family":"Harris","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (K.H., M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-6333","authenticated-orcid":true,"given":"Pablo","family":"Hervella","sequence":"additional","affiliation":[{"name":"Neuroimaging and Biotechnology Laboratory, Health Research Institute of Santiago de Compostela, Spain (P.H., R.I.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Iglesias-Rey","sequence":"additional","affiliation":[{"name":"Neuroimaging and Biotechnology Laboratory, Health Research Institute of Santiago de Compostela, Spain (P.H., R.I.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-2354","authenticated-orcid":true,"given":"Christina","family":"Jern","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Sweden (C.J., T.M.S.)."},{"name":"Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden (C.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-8066","authenticated-orcid":true,"given":"Mira","family":"Katan","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital of Zurich, Switzerland (M.A., M.K.)."},{"name":"Neurology Department, University Hospital Basel, Switzerland (G.M.D., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-8355","authenticated-orcid":true,"given":"Linxin","family":"Li","sequence":"additional","affiliation":[{"name":"Wolfson Centre for the Prevention of Stroke and Dementia (L.L., P.M.R.), University of Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3037-169X","authenticated-orcid":true,"given":"Nobukazu","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Neurology Department, Juntendo University School of Medicine, Tokyo, Japan (N.M., Y.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-2279","authenticated-orcid":true,"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain (J.M.)."},{"name":"Institute de Biomedicine of Seville, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/University of Seville, Spain (J.M.)."},{"name":"Virgen Macarena Hospital, Neurology, Sevilla, Spain (J.M.)."},{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research, Universitat Aut\u00f2noma de Barcelona, Spain (J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-5968","authenticated-orcid":true,"given":"Francisco","family":"Purroy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, Spain (F.P., M.V.-P.)."},{"name":"Department of Clinical Neurosciences, University of Lleida, Spain (F.P., M.V.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-9211","authenticated-orcid":true,"given":"Peter M.","family":"Rothwell","sequence":"additional","affiliation":[{"name":"Wolfson Centre for the Prevention of Stroke and Dementia (L.L., P.M.R.), University of Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-0407","authenticated-orcid":true,"given":"Tara M.","family":"Stanne","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Sweden (C.J., T.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7725-7520","authenticated-orcid":true,"given":"Catherine","family":"Sudlow","sequence":"additional","affiliation":[{"name":"Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics (C.S.), University of Edinburgh, United Kingdom."},{"name":"Centre for Clinical Brain Sciences (C.S., W.W.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8617-3695","authenticated-orcid":true,"given":"Yuji","family":"Ueno","sequence":"additional","affiliation":[{"name":"Neurology Department, Juntendo University School of Medicine, Tokyo, Japan (N.M., Y.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-7853","authenticated-orcid":true,"given":"Mikel","family":"Vicente-Pascual","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, Spain (F.P., M.V.-P.)."},{"name":"Department of Clinical Neurosciences, University of Lleida, Spain (F.P., M.V.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4816-8991","authenticated-orcid":true,"given":"William","family":"Whiteley","sequence":"additional","affiliation":[{"name":"Nuffield Department of Population Health (W.W.), University of Oxford, United Kingdom."},{"name":"Centre for Clinical Brain Sciences (C.S., W.W.), University of Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9800-5296","authenticated-orcid":true,"given":"Mark","family":"Woodward","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (K.H., M.W.)."},{"name":"The George Institute for Global Health, School of Public Health, Imperial College London, United Kingdom (M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-6565","authenticated-orcid":true,"given":"Peter J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin (J.J.M., C.W., S.G., P.J.K.)."},{"name":"School of Medicine, University College Dublin, Ireland (J.J.M., S.G., P.J.K.)."},{"name":"Stroke Service, Mater Misericordiae University Hospital, Dublin, Ireland (J.J.M., S.G., 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Induces Early Recurrent Vascular Events by Inflammasome-Dependent Atherosclerotic Plaque Rupture","author":"Cao J","year":"2023","unstructured":"Cao J, Roth S, Zhang S, Kopczak A, Georgakis MK, Li X, Dutsch A, Liman TG, Endres M, Brough D, et al. Stroke Induces Early Recurrent Vascular Events by Inflammasome-Dependent Atherosclerotic Plaque Rupture. Cold Spring Harbor Laboratory Press; 2023."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00968-1"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy310"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00520-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-018-1387-z"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02467"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.124.047820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T14:53:47Z","timestamp":1748530427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.124.047820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":21,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1161\/STROKEAHA.124.047820"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.124.047820","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-05-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}