Lanyue Zhang, Mohamad Ali Antabi, Jana Mattar, Omar El Bounkari, Rong Fang, Karin Waegemann, Felix J Bode, Sebastian Stösser, Peter Hermann, Thomas G Liman, Christian H Nolte, Benno Ikenberg, Kathleen Bernkopf, Wenzel Glanz, Daniel Janowitz, Annika Spottke, Michael Wolfgang Görtler, Silke Wunderlich, Inga Zerr, Gabor C Petzold, Matthias Endres, Jürgen Bernhagen, Martin Dichgans, Marios K Georgakis
{"title":"循环细胞因子水平与卒中后5年血管复发：一项多中心前瞻性队列研究。","authors":"Lanyue Zhang, Mohamad Ali Antabi, Jana Mattar, Omar El Bounkari, Rong Fang, Karin Waegemann, Felix J Bode, Sebastian Stösser, Peter Hermann, Thomas G Liman, Christian H Nolte, Benno Ikenberg, Kathleen Bernkopf, Wenzel Glanz, Daniel Janowitz, Annika Spottke, Michael Wolfgang Görtler, Silke Wunderlich, Inga Zerr, Gabor C Petzold, Matthias Endres, Jürgen Bernhagen, Martin Dichgans, Marios K Georgakis","doi":"10.1177/23969873251360145","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-inflammatory therapies are tested in randomized trials for secondary stroke prevention. Detecting inflammatory biomarkers that predict vascular recurrence could optimize patient selection for these trials.</p><p><strong>Methods: </strong>In a multicenter prospective cohort study, we measured plasma levels of 22 inflammatory cytokines in 486 acute stroke patients (474 ischemic strokes and 12 intracerebral hemorrhages; median age 68 years, 34% female, median 3 days post-stroke onset). Patients were followed for over 5 years through telephone and in-person interviews to record the occurrence of the following outcomes: (1) recurrent stroke or transient ischemic attack (TIA; primary outcome); (2) a composite of recurrent vascular events (stroke, TIA, acute coronary syndrome, hospital admission due to heart failure, and death; secondary outcome). Associations between cytokine levels and these outcomes were analyzed using Cox proportional hazards models adjusted for demographic and vascular risk factors.</p><p><strong>Results: </strong>During the 5-year follow-up period, 59 patients (12.1%) experienced recurrent stroke or TIA, and 118 (24.3%) experienced recurrent vascular events. After adjustments for demographic and vascular risk factors, and correction for multiple comparisons, higher plasma levels of CD62E (adjusted Hazard Ratio (aHR)/SD increment: 1.63, 95%CI 1.22-2.20) and MIF (aHR: 1.56, 95%CI 1.18-2.06) in the acute phase after stroke were statistically significantly associated with increased risk of recurrent stroke or TIA. The associations followed a dose-response pattern across quartiles of CD62E and MIF levels. Adding baseline CD62E and MIF levels to models including age, sex, vascular risk factors, and baseline C-reactive protein (CRP) levels led to significant improvements in the prediction of 5-year risk of recurrent stroke or TIA (ΔC-index 0.030-0.050).</p><p><strong>Conclusion: </strong>Among stroke patients, higher baseline levels of CD62E and MIF improved prediction of 5-year risk of recurrent stroke or TIA on top of vascular risk factors and CRP levels. Whether assessment of these cytokines could improve patient selection for secondary prevention trials of anti-inflammatory treatments, should be explored in future studies.</p>","PeriodicalId":46821,"journal":{"name":"European Stroke Journal","volume":" ","pages":"23969873251360145"},"PeriodicalIF":4.5000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343552/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating cytokine levels and 5-year vascular recurrence after stroke: A multicenter prospective cohort study.\",\"authors\":\"Lanyue Zhang, Mohamad Ali Antabi, Jana Mattar, Omar El Bounkari, Rong Fang, Karin Waegemann, Felix J Bode, Sebastian Stösser, Peter Hermann, Thomas G Liman, Christian H Nolte, Benno Ikenberg, Kathleen Bernkopf, Wenzel Glanz, Daniel Janowitz, Annika Spottke, Michael Wolfgang Görtler, Silke Wunderlich, Inga Zerr, Gabor C Petzold, Matthias Endres, Jürgen Bernhagen, Martin Dichgans, Marios K Georgakis\",\"doi\":\"10.1177/23969873251360145\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Anti-inflammatory therapies are tested in randomized trials for secondary stroke prevention. Detecting inflammatory biomarkers that predict vascular recurrence could optimize patient selection for these trials.</p><p><strong>Methods: </strong>In a multicenter prospective cohort study, we measured plasma levels of 22 inflammatory cytokines in 486 acute stroke patients (474 ischemic strokes and 12 intracerebral hemorrhages; median age 68 years, 34% female, median 3 days post-stroke onset). Patients were followed for over 5 years through telephone and in-person interviews to record the occurrence of the following outcomes: (1) recurrent stroke or transient ischemic attack (TIA; primary outcome); (2) a composite of recurrent vascular events (stroke, TIA, acute coronary syndrome, hospital admission due to heart failure, and death; secondary outcome). Associations between cytokine levels and these outcomes were analyzed using Cox proportional hazards models adjusted for demographic and vascular risk factors.</p><p><strong>Results: </strong>During the 5-year follow-up period, 59 patients (12.1%) experienced recurrent stroke or TIA, and 118 (24.3%) experienced recurrent vascular events. After adjustments for demographic and vascular risk factors, and correction for multiple comparisons, higher plasma levels of CD62E (adjusted Hazard Ratio (aHR)/SD increment: 1.63, 95%CI 1.22-2.20) and MIF (aHR: 1.56, 95%CI 1.18-2.06) in the acute phase after stroke were statistically significantly associated with increased risk of recurrent stroke or TIA. The associations followed a dose-response pattern across quartiles of CD62E and MIF levels. Adding baseline CD62E and MIF levels to models including age, sex, vascular risk factors, and baseline C-reactive protein (CRP) levels led to significant improvements in the prediction of 5-year risk of recurrent stroke or TIA (ΔC-index 0.030-0.050).</p><p><strong>Conclusion: </strong>Among stroke patients, higher baseline levels of CD62E and MIF improved prediction of 5-year risk of recurrent stroke or TIA on top of vascular risk factors and CRP levels. Whether assessment of these cytokines could improve patient selection for secondary prevention trials of anti-inflammatory treatments, should be explored in future studies.</p>\",\"PeriodicalId\":46821,\"journal\":{\"name\":\"European Stroke Journal\",\"volume\":\" \",\"pages\":\"23969873251360145\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343552/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Stroke Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/23969873251360145\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Stroke Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/23969873251360145","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Circulating cytokine levels and 5-year vascular recurrence after stroke: A multicenter prospective cohort study.
Background and objectives: Anti-inflammatory therapies are tested in randomized trials for secondary stroke prevention. Detecting inflammatory biomarkers that predict vascular recurrence could optimize patient selection for these trials.
Methods: In a multicenter prospective cohort study, we measured plasma levels of 22 inflammatory cytokines in 486 acute stroke patients (474 ischemic strokes and 12 intracerebral hemorrhages; median age 68 years, 34% female, median 3 days post-stroke onset). Patients were followed for over 5 years through telephone and in-person interviews to record the occurrence of the following outcomes: (1) recurrent stroke or transient ischemic attack (TIA; primary outcome); (2) a composite of recurrent vascular events (stroke, TIA, acute coronary syndrome, hospital admission due to heart failure, and death; secondary outcome). Associations between cytokine levels and these outcomes were analyzed using Cox proportional hazards models adjusted for demographic and vascular risk factors.
Results: During the 5-year follow-up period, 59 patients (12.1%) experienced recurrent stroke or TIA, and 118 (24.3%) experienced recurrent vascular events. After adjustments for demographic and vascular risk factors, and correction for multiple comparisons, higher plasma levels of CD62E (adjusted Hazard Ratio (aHR)/SD increment: 1.63, 95%CI 1.22-2.20) and MIF (aHR: 1.56, 95%CI 1.18-2.06) in the acute phase after stroke were statistically significantly associated with increased risk of recurrent stroke or TIA. The associations followed a dose-response pattern across quartiles of CD62E and MIF levels. Adding baseline CD62E and MIF levels to models including age, sex, vascular risk factors, and baseline C-reactive protein (CRP) levels led to significant improvements in the prediction of 5-year risk of recurrent stroke or TIA (ΔC-index 0.030-0.050).
Conclusion: Among stroke patients, higher baseline levels of CD62E and MIF improved prediction of 5-year risk of recurrent stroke or TIA on top of vascular risk factors and CRP levels. Whether assessment of these cytokines could improve patient selection for secondary prevention trials of anti-inflammatory treatments, should be explored in future studies.
期刊介绍：
Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.
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