中性粒细胞与淋巴细胞比值对急性缺血性卒中静脉溶栓患者预后的预测价值：基于3项随机对照试验的个体患者数据分析

doi:10.3969/j.issn.1673-5765.2026.01.004

中国卒中杂志 ›› 2026, Vol. 21 ›› Issue (1): 38-47.DOI: 10.3969/j.issn.1673-5765.2026.01.004

中性粒细胞与淋巴细胞比值对急性缺血性卒中静脉溶栓患者预后的预测价值：基于3项随机对照试验的个体患者数据分析

何丹丹^1，2，冯宝玉¹，刘改芬^3，4，谷鸿秋³，李姝雅^1，3，4

1北京 100070 首都医科大学附属北京天坛医院临床试验中心
2北京 100070 首都医科大学临床流行病学与临床试验学系
3北京 100070 首都医科大学附属北京天坛医院神经系统疾病国家临床医学研究中心
4北京 100070 首都医科大学附属北京天坛医院神经病学中心

收稿日期:2025-10-28 修回日期:2026-01-09 接受日期:2026-01-15 出版日期:2026-01-20 发布日期:2026-01-20
通讯作者: 李姝雅 shuyali85@163.com
基金资助:
国家自然科学基金青年科学基金项目（B类）（82522025）

Predictive Value of the Neutrophil-to-Lymphocyte Ratio for Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis: An Individual Patient Data Analysis Based on Three Randomized Controlled Trials

HE Dandan^1,2, FENG Baoyu¹, LIU Gaifen^3,4, GU Hongqiu³, LI Shuya^1,3,4

1 Department of Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China 2 Department of Clinical Epidemiology and Clinical Trial, Capital Medical University, Beijing 100070, China 3 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China 4 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2025-10-28 Revised:2026-01-09 Accepted:2026-01-15 Online:2026-01-20 Published:2026-01-20
Contact: LI Shuya, E-mail: shuyali85@163.com

摘要/Abstract

摘要： 目的分析发病4.5 h内急性缺血性卒中（acute ischemic stroke，AIS）患者静脉溶栓前、静脉溶栓后24 h和静脉溶栓后7 d中性粒细胞与淋巴细胞比值（neutrophil-to-lymphocyte ratio，NLR）与90 d预后不良的关系。
方法本研究整合了2021年3月—2024年3月在中国开展的3项Ⅲ期临床研究（TRACE-Ⅱ、RAISE、PROST-2）中发病4.5 h内接受静脉溶栓治疗的AIS患者数据。根据静脉溶栓后90 d mRS评分，将患者分为预后良好（mRS评分为0～1分）组与预后不良（mRS评分为2～6分）组。收集两组患者的年龄、性别、既往病史等基线特征，以及静脉溶栓前、静脉溶栓后24 h和静脉溶栓后7 d的炎症指标（包括白细胞计数、淋巴细胞计数、中性粒细胞计数、NLR、系统性免疫炎症指数、血小板与淋巴细胞比值、血小板与中性粒细胞比值）。通过ROC曲线的AUC评估各项炎症指标对AIS患者静脉溶栓后90 d预后不良的预测价值。通过多因素logistic回归分析和限制性立方样条模型，分析NLR与AIS患者静脉溶栓后90 d预后不良之间的关联。
结果共纳入4273例AIS患者。在不同时间点检测的7项炎症指标中，静脉溶栓后24 h NLR对90 d预后不良的预测效能最佳（AUC 0.69）。多因素logistic回归分析显示，NLR升高与90 d预后不良风险增加相关（OR 1.17，95%CI 1.14～1.21，P<0.001）。在校正潜在混杂因素后，NLR≥3.21的患者较NLR<3.21的患者90 d预后不良风险增加1.55倍（OR 2.55，95%CI 2.19～2.97，P<0.001）。限制性立方样条分析显示，AIS患者静脉溶栓后24 h NLR与90 d预后不良风险之间存在正向非线性关联（P<0.001）。
结论在标准时间窗内接受静脉溶栓治疗的AIS患者中，以NLR＝3.21作为截断值可识别预后不良的高风险人群，为临床进行个体化干预提供了简便、客观的参考依据。

文章导读： 本研究在多种静脉溶栓药物（阿替普酶、替奈普酶、瑞替普酶、尿激酶原）中，验证了中性粒细胞与淋巴细胞比值对标准时间窗内接受静脉溶栓治疗的AIS患者90 d预后不良的预测价值。其中静脉溶栓后24 h中性粒细胞与淋巴细胞比值≥3.21可用于预测预后不良的高风险人群。该指标检测便捷、成本低廉，为临床AIS患者的个体化干预及抗炎治疗获益人群筛选提供了可靠参考，具有重要的临床推广价值。

关键词: 急性缺血性卒中; 炎症指标; 静脉溶栓; 个体患者数据分析; 中性粒细胞与淋巴细胞比值

Abstract: Objective To analyze the association between the neutrophil-to-lymphocyte ratio (NLR) before intravenous thrombolysis, at 24 hours and 7 days after intravenous thrombolysis and poor prognosis at 90 days in patients with acute ischemic stroke (AIS) within 4.5 hours of onset.
Methods This study integrated data of AIS patients who received intravenous thrombolysis within 4.5 hours of onset from three phase Ⅲ clinical trials (TRACE-Ⅱ, RAISE, PROST-2) conducted in China between March 2021 and March 2024. According to the mRS score at 90 days after intravenous thrombolysis, patients were divided into a favorable prognosis (mRS score 0-1) group and a poor prognosis (mRS score 2-6) group. Baseline characteristics including age, gender, and past medical history, as well as inflammatory indicators before intravenous thrombolysis, at 24 hours and 7 days after intravenous thrombolysis were collected for both groups. The inflammatory indicators included white blood cell count, lymphocyte count, neutrophil count, NLR, systemic immune inflammation index, platelet-to-lymphocyte ratio, and platelet-to-neutrophil ratio. The AUC was used to evaluate the predictive value of each inflammatory indicator for poor prognosis at 90 days in AIS patients after intravenous thrombolysis. Multivariate logistic regression analysis and restricted cubic spline model were applied to analyze the association between NLR and poor prognosis at 90 days in AIS patients after intravenous thrombolysis.
Results A total of 4273 AIS patients were enrolled. Among the seven inflammatory indicators measured at different time points, NLR at 24 hours after intravenous thrombolysis showed the best predictive efficacy for poor prognosis at 90 days (AUC 0.69). Multivariate logistic regression analysis indicated that elevated NLR was associated with an increased risk of poor prognosis at 90 days (OR 1.17, 95%CI 1.14-1.21, P<0.001). After adjusting for potential confounding factors, patients with NLR≥3.21 had a 1.55-fold higher risk of poor prognosis at 90 days compared to those with NLR<3.21 (OR 2.55, 95%CI 2.19-2.97, P<0.001). Restricted cubic spline analysis revealed a positive nonlinear relationship between NLR at 24 hours after intravenous thrombolysis and the risk of poor prognosis at 90 days in AIS patients (P<0.001).
Conclusions For AIS patients receiving intravenous thrombolysis within the standard time window, an NLR cutoff value of 3.21 can identify high risk populations with poor prognosis, providing a simple and objective reference for individualized clinical intervention.

Key words: Acute ischemic stroke; Inflammatory indicator; Intravenous thrombolysis; Individual patient data analysis; Neutrophil-to-lymphocyte ratio

中图分类号:

何丹丹, 冯宝玉, 刘改芬, 谷鸿秋, 李姝雅. 中性粒细胞与淋巴细胞比值对急性缺血性卒中静脉溶栓患者预后的预测价值：基于3项随机对照试验的个体患者数据分析[J]. 中国卒中杂志, 2026, 21(1): 38-47.

HE Dandan, FENG Baoyu, LIU Gaifen, GU Hongqiu, LI Shuya. Predictive Value of the Neutrophil-to-Lymphocyte Ratio for Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis: An Individual Patient Data Analysis Based on Three Randomized Controlled Trials[J]. Chinese Journal of Stroke, 2026, 21(1): 38-47.

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中性粒细胞与淋巴细胞比值对急性缺血性卒中静脉溶栓患者预后的预测价值：基于3项随机对照试验的个体患者数据分析

Predictive Value of the Neutrophil-to-Lymphocyte Ratio for Prognosis in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis: An Individual Patient Data Analysis Based on Three Randomized Controlled Trials

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