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, China.
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, China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Nutr Metab Cardiovasc Dis. 2021 Mar 10;31(3):852-859. doi: 10.1016/j.numecd.2020.11.004. Epub 2020 Nov 12.
High serum netrin-1 levels decrease the risk of ischemic stroke and are negatively associated with outcomes after ischemic stroke. However, it remains unclear whether the association between netrin-1 and ischemic stroke prognosis is modified by lipid component levels.
We measured baseline serum netrin-1 levels in 3065 ischemic stroke patients from China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score≥3) at 3 months after ischemic stroke. Total cholesterol (TC) levels could modify the association between netrin-1 and prognosis of ischemic stroke (P = 0.040). After multivariate adjustment, the odds ratios of the primary outcome associated with the highest quartile of netrin-1 were 0.39 (95%CI, 0.17-0.90; P = 0.004) for the patients with high TC levels and 0.82 (95%CI, 0.61-1.11; P = 0.149) for those with normal TC levels. Adding netrin-1 to conventional risk factors improved risk prediction for the primary outcome in the patients with high TC levels (net reclassification improvement: 26.8%, P = 0.015; integrated discrimination index: 1.6%, P = 0.028) but not in those with normal TC levels.
Elevated netrin-1 is associated with improved prognosis at 3 months after ischemic stroke in the patients with high TC levels but not in those with normal TC levels. Further prospective studies from other populations and randomized clinical trials are needed to verify our findings and clarify the potential mechanisms.
血清 netrin-1 水平升高可降低缺血性脑卒中风险，并与缺血性脑卒中后结局呈负相关。然而，netrin-1 与缺血性脑卒中预后之间的关联是否受脂质成分水平的影响尚不清楚。
我们在中国急性缺血性脑卒中降压试验（CATIS）中测量了 3065 例缺血性脑卒中患者的基线血清 netrin-1 水平。主要结局为缺血性脑卒中后 3 个月时死亡和主要残疾（改良 Rankin 量表评分≥3）的联合终点。总胆固醇（TC）水平可能会改变 netrin-1 与缺血性脑卒中预后之间的关联（P=0.040）。经过多变量调整后，netrin-1 最高四分位数与主要结局相关的比值比（OR）为高 TC 水平患者的 0.39（95%CI，0.17-0.90；P=0.004）和 TC 水平正常患者的 0.82（95%CI，0.61-1.11；P=0.149）。在高 TC 水平患者中，将 netrin-1 添加到常规危险因素中可改善主要结局的风险预测（净重新分类改善：26.8%，P=0.015；综合判别指数：1.6%，P=0.028），但在 TC 水平正常的患者中则不然。
在 TC 水平升高的患者中，升高的 netrin-1 与缺血性脑卒中后 3 个月的预后改善相关，但在 TC 水平正常的患者中则不然。需要来自其他人群的进一步前瞻性研究和随机临床试验来验证我们的发现并阐明潜在机制。
