Yuhan Zang1, Daoxia Guo2, Lihua Chen1, Pinni Yang1, Zhengbao Zhu2, Xiaoqing Bu3, Tian Xu4, Chongke Zhong1, Aili Wang1, Hao Peng1, Tan Xu1, Jing Chen5, Yonghong Zhang6, Jiang He5. 1. 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. 2. 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. 3. 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, Chongqing Medical University, Chongqing, China. 4. 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 Neurology, Affiliated Hospital of Nantong University, Nantong, China. 5. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. 6. 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. Electronic address: yhzhang@suda.edu.cn.
Abstract
BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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 (Pinteraction = 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; Ptrend = 0.004) for the patients with high TC levels and 0.82 (95%CI, 0.61-1.11; Ptrend = 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS AND RESULTS: We measured baseline serum netrin-1 levels in 3065 ischemic strokepatients 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 (Pinteraction = 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; Ptrend = 0.004) for the patients with high TC levels and 0.82 (95%CI, 0.61-1.11; Ptrend = 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. CONCLUSIONS: 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.