Zhang Lanyue, Antabi Mohamad Ali, Mattar Jana, Bounkari Omar El, Fang Rong, Waegemann Karin, Bode Felix J, Stösser Sebastian, Hermann Peter, Liman Thomas G, Nolte Christian H, Ikenberg Benno, Bernkopf Kathleen, Glanz Wenzel, Janowitz Daniel, Spottke Annika, Görtler Michael Wolfgang, Wunderlich Silke, Zerr Inga, Petzold Gabor C, Endres Matthias, Bernhagen Jürgen, Dichgans Martin, Georgakis Marios K
Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Eur Stroke J. 2025 Aug 11:23969873251360145. doi: 10.1177/23969873251360145.
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.
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.
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).
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.
抗炎疗法在二级卒中预防的随机试验中进行了测试。检测可预测血管性复发的炎症生物标志物可优化这些试验的患者选择。
在一项多中心前瞻性队列研究中，我们测量了486例急性卒中患者（474例缺血性卒中和12例脑出血；中位年龄68岁，34%为女性，卒中发病后中位3天）血浆中22种炎症细胞因子的水平。通过电话和面对面访谈对患者进行了5年多的随访，以记录以下结局的发生情况：（1）复发性卒中或短暂性脑缺血发作（TIA；主要结局）；（2）复发性血管事件的复合结局（卒中、TIA、急性冠状动脉综合征、因心力衰竭住院和死亡；次要结局）。使用针对人口统计学和血管危险因素进行调整的Cox比例风险模型分析细胞因子水平与这些结局之间的关联。
在5年随访期内，59例患者（12.1%）发生了复发性卒中或TIA，118例患者（24.3%）发生了复发性血管事件。在对人口统计学和血管危险因素进行调整并校正多重比较后，卒中急性期较高的血浆CD62E水平（调整后风险比（aHR）/标准差增量：1.63，95%置信区间1.22 - 2.20）和MIF水平（aHR：1.56，95%置信区间1.18 - 2.06）与复发性卒中或TIA风险增加在统计学上显著相关。这些关联在CD62E和MIF水平的四分位数中呈剂量反应模式。将基线CD62E和MIF水平添加到包括年龄、性别、血管危险因素和基线C反应蛋白（CRP）水平的模型中，可显著改善对复发性卒中或TIA 5年风险的预测（ΔC指数0.030 - 0.050）。
在卒中患者中，较高的基线CD62E和MIF水平在血管危险因素和CRP水平之上，改善了对复发性卒中或TIA 5年风险的预测。这些细胞因子的评估是否可改善抗炎治疗二级预防试验的患者选择，应在未来研究中进行探索。
