Liu Zhuohang, Chu Min, Zhang Zengyu, Zhao Jing
Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China.
Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, China.
Int J Med Sci. 2025 Jul 25;22(13):3464-3476. doi: 10.7150/ijms.108310. eCollection 2025.
Total bile acids (TBAs) are emerging as potential prognostic biomarkers in acute ischemic stroke (AIS). This study aimed to evaluate the association between TBA levels and long-term outcomes in AIS patients receiving intravenous thrombolysis (IVT). A total of 231 AIS patients treated with IVT were prospectively enrolled. TBA levels were measured on admission. The primary outcome was the 3-month modified Rankin Scale (mRS) score. Logistic regression, restricted cubic splines (RCS), and decision curve analysis (DCA) were used to assess associations. Machine learning (ML) models were employed to validate predictive performance. High TBA (> 5 μmol/L) patients showed significantly better functional outcomes (91.2% vs 60.2%, P < 0.001). Multivariate analysis confirmed higher TBA independently predicted favorable outcomes (adjusted OR = 0.74, 95%CI:0.59-0.93), with TBA-integrated models showing superior discrimination (AUC = 0.970 vs ≤ 0.64 for NIHSS/TOAST). Restricted cubic spline analysis revealed a J-shaped non-linear relationship between TBA levels and outcome probability. Critically, a predictive model combining TBA with clinical factors demonstrated superior discriminative ability (AUC = 0.970), significantly outperforming traditional scores (NIHSS AUC = 0.64; TOAST AUC = 0.55). Decision curve analysis confirmed the model's clinical utility. Machine learning validation, particularly using Random Forest (accuracy: 93.8%, AUC: 93.14%, Brier score: 0.072), further substantiated TBA's predictive value. Feature importance analysis identified TBA (25.85) and hemoglobin (24.34) as the primary predictors, substantially exceeding others (e.g., NT-proBNP:3.60; admission NIHSS: 3.41; eGFR-EPI: 3.28). TBA is independently associated with functional outcomes after IVT and may serve as a novel prognostic biomarker in AIS.
总胆汁酸(TBAs)正逐渐成为急性缺血性卒中(AIS)潜在的预后生物标志物。本研究旨在评估接受静脉溶栓(IVT)的AIS患者中TBA水平与长期预后之间的关联。前瞻性纳入了总共231例接受IVT治疗的AIS患者。入院时测量TBA水平。主要结局为3个月改良Rankin量表(mRS)评分。采用逻辑回归、限制性立方样条(RCS)和决策曲线分析(DCA)来评估关联。使用机器学习(ML)模型验证预测性能。高TBA(>5 μmol/L)患者显示出显著更好的功能结局(91.2% 对60.2%,P < 0.001)。多变量分析证实较高的TBA独立预测良好结局(校正OR = 0.74,95%CI:0.59 - 0.93),TBA整合模型显示出更好的辨别力(AUC = 0.970,而NIHSS/TOAST的AUC≤0.64)。限制性立方样条分析显示TBA水平与结局概率之间呈J形非线性关系。关键的是,一个将TBA与临床因素相结合的预测模型显示出卓越的辨别能力(AUC = 0.970),显著优于传统评分(NIHSS的AUC = 0.64;TOAST的AUC = 0.55)。决策曲线分析证实了该模型的临床实用性。机器学习验证,特别是使用随机森林(准确率:93.8%,AUC:93.14%,Brier评分:0.072),进一步证实了TBA的预测价值。特征重要性分析确定TBA(25.85)和血红蛋白(24.34)为主要预测因素,大大超过其他因素(例如,NT - proBNP:3.60;入院时NIHSS:3.41;eGFR - EPI:3.28)。TBA与IVT后的功能结局独立相关,可能作为AIS中的一种新型预后生物标志物。