Increased Serum Netrin-1 Is Associated With Improved Prognosis of Ischemic Stroke

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 trend =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 linearity =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.