Shen Tong, Fan Junfen, Zheng Yangmin, Luo Yumin, Liu Ping
Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China.
Mol Neurobiol. 2025 Apr;62(4):4292-4300. doi: 10.1007/s12035-024-04556-z. Epub 2024 Oct 23.
Complete blood cell count (CBC) is the most common and readily available laboratory test in clinical practice. The relationships of some CBC indices with ischemic stroke have been reported in observational studies; however, the causal direction is not specified. This study aimed to explore the causal relationships between CBC indices and the modified Rankin Scale (mRS) score at 3 months after ischemic stroke. Genetic associations of 22 blood cell traits were obtained from the UK Biobank database (n = 350,475). The outcome data for ischemic stroke were obtained from the Genetic Ischemic Stroke Functional Outcome (GISCOME) network (n = 6021). We implemented two-sample Mendelian randomization (TSMR) and several complementary analyses to assess the causal association between blood traits and unfavorable outcome (3-month mRS > 2). The clinical cohort was validated based on the results of the MR analysis. TSMR result indicated causal association between genetically determined platelet distribution width (PDW) and adverse functional outcome after ischemic stroke (OR 1.48; 95% CI 1.13-1.95; p = 0.005). Complementary analyses showed negligible causal effect of genetic variants on stroke subtypes. In cohort study (n = 351), higher level of PDW was observed in the unfavorable outcome group. However, the multivariable logistic regression analysis failed to identify the improvement in predictive performance of stroke outcomes by adding PDW to the prediction model. Further correlation analysis revealed that PDW is positively correlated with serum glucose levels, and the level of PDW in the non-thrombolysed group was significantly higher than that in the thrombolysis group, indicating that PDW may be involved in stroke prognosis in an indirect way.
全血细胞计数(CBC)是临床实践中最常见且最容易获得的实验室检查。在观察性研究中已报道了一些CBC指标与缺血性卒中的关系;然而,因果方向并不明确。本研究旨在探讨缺血性卒中后3个月时CBC指标与改良Rankin量表(mRS)评分之间的因果关系。从英国生物银行数据库(n = 350475)中获取了22种血细胞特征的遗传关联数据。缺血性卒中的结局数据来自遗传缺血性卒中功能结局(GISCOME)网络(n = 6021)。我们实施了两样本孟德尔随机化(TSMR)和多项补充分析,以评估血液特征与不良结局(3个月mRS>2)之间的因果关联。基于MR分析结果对临床队列进行了验证。TSMR结果表明,遗传决定的血小板分布宽度(PDW)与缺血性卒中后的不良功能结局之间存在因果关联(OR 1.48;95%CI 1.13 - 1.95;p = 0.005)。补充分析显示,基因变异对卒中亚型的因果效应可忽略不计。在队列研究(n = 351)中,不良结局组中观察到较高水平的PDW。然而,多变量逻辑回归分析未能通过将PDW添加到预测模型中来识别卒中结局预测性能的改善。进一步的相关性分析显示,PDW与血清葡萄糖水平呈正相关,且未溶栓组的PDW水平显著高于溶栓组,表明PDW可能以间接方式参与卒中预后。