{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:40:54Z","timestamp":1788316854832,"version":"build-2803163510"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Uncertainty remains whether inflammation is implicated in poststroke recurrence in patients without atherosclerosis. We evaluated the contribution of atherosclerosis status to the association between inflammatory markers and major adverse cardiovascular events (MACE) poststroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We performed an individual-participant data meta-analysis of 11 prospective cohorts (12 countries, 1995\u20132017). Studies included patients with ischemic stroke\/transient ischemic attack and measured IL (interleukin)-6\/hsCRP (high-sensitivity C-reactive protein) postevent. We analyzed the association between IL-6\/hsCRP and recurrent stroke\/MACE using multivariable Cox regression analyses (conditional logistic regression for 1 study). Analyses were stratified by the presence\/absence of atherosclerosis (definition: prior history of coronary disease, peripheral artery disease, or large artery atherosclerotic stroke) and adjusted for cardiovascular risk factors\/preventative medication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Overall 10\u2009148 patients (3448 [34.0%] had atherosclerosis) with 21\u2009177 years of follow-up were included (1707 MACE outcomes\/1353 recurrent strokes). In patients with atherosclerosis, IL-6 was independently associated with MACE (risk ratio [RR], 1.22 [95% CI, 1.08\u20131.37]; per log\n                      <jats:sub>e<\/jats:sub>\n                      unit increase) and recurrent stroke (RR, 1.23 [95% CI, 1.08\u20131.41]). Compared with patients in the bottom quarter, those in the top quarter of IL-6 levels had double the risk of MACE (RR, 2.05 [95% CI, 1.37\u20133.08]) and stroke (RR, 1.97 [95% CI, 1.28\u20133.05]). IL-6 was also associated with MACE (RR, 1.11 [95% CI, 1.01\u20131.23]) but not stroke (RR, 1.08 [95% CI, 0.98\u20131.20]; per log\n                      <jats:sub>e<\/jats:sub>\n                      unit) in patients without atherosclerosis. However, there was no evidence of statistical interaction between IL-6 levels and atherosclerosis status for either outcome (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.25 and 0.13 for MACE\/recurrent stroke, respectively). hsCRP was associated with MACE in patients with (RR, 1.12 [95% CI, 1.05\u20131.21]; per log\n                      <jats:sub>e<\/jats:sub>\n                      unit) and without atherosclerosis (RR, 1.07 [95% CI, 1.01\u20131.14];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.28). No association with recurrent stroke was observed for hsCRP with (RR, 1.06 [95% CI, 0.98\u20131.14]) or without atherosclerosis (RR, 0.97 [95% CI, 0.91\u20131.04];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.18).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>IL-6\/hsCRP were associated with poststroke recurrence irrespective of atherosclerosis. These data support the inclusion of patients in trials of anti-inflammatory therapies after stroke with elevated IL-6 or hsCRP, including those without prior atherosclerotic events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.052091","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T09:00:27Z","timestamp":1752829227000},"page":"2588-2596","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-6, C-Reactive Protein, and Vascular Recurrence After Stroke With and Without Atherosclerosis"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-1303","authenticated-orcid":true,"given":"John J.","family":"McCabe","sequence":"first","affiliation":[{"name":"Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (J.J.M., C.W., S.G., P.J.K.)."},{"name":"School of Medicine, University College Dublin (UCD), 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\/0000-0003-2444-2869","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"}]},{"given":"Cathal","family":"Walsh","sequence":"additional","affiliation":[{"name":"Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (J.J.M., C.W., S.G., P.J.K.)."},{"name":"Department of Biostatistics, Trinity College Dublin, Ireland (C.W., M.K.)."}],"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 (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (J.J.M., C.W., S.G., P.J.K.)."},{"name":"School of Medicine, University College Dublin (UCD), 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":"De Marchis","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital Basel, Switzerland (G.M.D.M.)."},{"name":"Neurology Clinic and Stroke Center, University Teaching and Research Hospital St. Gallen, Switzerland (G.M.D.M.)."}],"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 (NOBEL), 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 (NOBEL), 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":"Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden (C.J., T.M.S.)."},{"name":"Department of Clinical Genetics and Genomics, Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Gothenburg, Sweden (C.J., T.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-8066","authenticated-orcid":true,"given":"Mira","family":"Katan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Trinity College Dublin, Ireland (C.W., M.K.)."},{"name":"Neurology Department, University Hospital of Zurich, Switzerland (M.A., 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IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/University of Seville, Spain (J.M.)."},{"name":"Neurology, Virgen Macarena Hospital, 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":"Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden (C.J., T.M.S.)."},{"name":"Department of Clinical Genetics and Genomics, Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Gothenburg, Sweden (C.J., T.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7725-7520","authenticated-orcid":true,"given":"Cathie","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 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