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We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A<jats:sub>2<\/jats:sub> mass (Lp-PLA<jats:sub>2<\/jats:sub>) and activity (Lp-PLA<jats:sub>2<\/jats:sub>-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2\u20136 within 1\u00a0year.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1\u00a0year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13\u20131.64; <jats:italic>P<\/jats:italic>\u2009=\u20090.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17\u20131.69; <jats:italic>P<\/jats:italic>\u2009=\u20090.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06\u20131.56; <jats:italic>P<\/jats:italic>\u2009=\u20090.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64\u20132.27; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37\u20131.87; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37\u20131.86; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03\u20131.42; <jats:italic>P<\/jats:italic>\u2009=\u20090.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19\u20131.52; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001; YKL-40: OR, 1.01; 95% CI 1.01\u20131.03; <jats:italic>P<\/jats:italic>\u2009=\u20090.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46\u20131.93; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001; YKL-40: OR, 1.02; 95% CI 1.01\u20131.03; <jats:italic>P<\/jats:italic>\u2009=\u20090.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) and Totaled Health Risks in Vascular Events Score (0.07, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), and yielded continuous net reclassification improvement (19.0%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001; 33.0, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-022-02467-1","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T06:03:13Z","timestamp":1656309793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study"],"prefix":"10.1186","volume":"19","author":[{"given":"Jiejie","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuesong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingquan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqiang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CNSR-III Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"2467_CR1","doi-asserted-by":"crossref","unstructured":"Boulanger M, Bejot Y, Rothwell PM, Touze E. 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