From the Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, Jiangsu, China (D.G., Z.Z., C.Z., H.P., A.W., Y.Z., Tan Xu, Y.Z.).
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (Z.Z., C.Z., C.-S.C., J.C., J.H.).
Stroke. 2019 Apr;50(4):845-852. doi: 10.1161/STROKEAHA.118.024631.
Background and Purpose- Previous experimental studies suggested that serum netrin-1 was associated with the progression of ischemic stroke. Knowledge about netrin-1 among ischemic stroke patients may provide new ideas for the prognostic assessment of ischemic stroke. The aim of this study was to investigate the association between serum netrin-1 and prognosis of ischemic stroke. Methods- Serum netrin-1 levels at baseline were measured for 3346 ischemic stroke patients from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke), and all patients were followed up at 3 months after stroke onset. The primary outcome was a combination of death and major disability (modified Rankin Scale score of ≥3) within 3 months after stroke onset. Results- Up to 3 months after stroke onset, 845 patients (25.25%) experienced death or major disability. After adjustment for baseline National Institutes of Health Stroke Scale score and other potential confounders, elevated serum netrin-1 was associated with a decreased risk of primary outcome (odds ratio, 0.65; 95% CI, 0.47-0.88; P=0.002) when 2 extreme quartiles were compared. Each SD increase of log-transformed netrin-1 was associated with 17% (95% CI, 7%-26%) decreased risk of primary outcome. Multivariable-adjusted spline regression models showed a negative linear dose-response relationship between serum netrin-1 and the risk of primary outcome ( P=0.003). Adding netrin-1 quartile to a model containing conventional risk factors improved risk prediction for primary outcome (net reclassification improvement index =14.74%; P=0.002; integrated discrimination improvement =0.40%; P=0.005). Conclusions- Elevated serum netrin-1 levels were associated with improved prognosis at 3 months after ischemic stroke, suggesting that serum netrin-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of ischemic stroke patients are needed to replicate our findings and to clarify the potential mechanisms. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01840072.
背景与目的- 先前的实验研究表明，血清 netrin-1 与缺血性脑卒中的进展有关。了解缺血性脑卒中患者的 netrin-1 可能为缺血性脑卒中的预后评估提供新的思路。本研究旨在探讨血清 netrin-1 与缺血性脑卒中预后的关系。方法- 从 CATIS（中国急性缺血性脑卒中抗高血压试验）中纳入 3346 例缺血性脑卒中患者，于基线时测量血清 netrin-1 水平，所有患者均在脑卒中发病后 3 个月进行随访。主要结局为脑卒中发病后 3 个月内死亡和主要残疾（改良 Rankin 量表评分≥3）的组合。结果- 脑卒中发病后 3 个月内，845 例患者（25.25%）发生死亡或主要残疾。在校正基线国立卫生研究院脑卒中量表评分和其他潜在混杂因素后，与 2 个极值四分位相比，升高的血清 netrin-1 与主要结局风险降低相关（比值比，0.65；95%置信区间，0.47-0.88；P=0.002）。log 转换后 netrin-1 的每个 SD 增加与主要结局风险降低 17%（95%置信区间，7%-26%）相关。多变量调整的样条回归模型显示血清 netrin-1 与主要结局风险之间存在负线性剂量-反应关系（P=0.003）。将 netrin-1 四分位数添加到包含常规危险因素的模型中可改善主要结局的风险预测（净重新分类改善指数=14.74%；P=0.002；综合判别改善=0.40%；P=0.005）。结论- 缺血性脑卒中后 3 个月，升高的血清 netrin-1 水平与预后改善相关，提示血清 netrin-1 可能是缺血性脑卒中的潜在预后生物标志物。需要来自其他缺血性脑卒中患者样本的进一步研究来复制我们的发现并阐明潜在机制。临床试验注册- URL：https://www.clinicaltrials.gov。独特标识符：NCT01840072。
