【摘要】 目的 探讨二氧化氮（nitrogen dioxide,NO₂）长期暴露与缺血性脑卒中（ischemic stroke,IS）患者死亡风险之间的关联以及绿地暴露的效应修饰作用。方法 选取山东省NO₂浓度相对较高的西北地区4个区（县）2013―2019年的IS病例进行了纵向研究，患者被随访至2019年12月31日或死亡日期。采用时间依赖Cox比例风险回归模型，评估NO₂每增加1个IQR,IS患者因脑卒中死亡的HR及其95%CI。利用限制性三次立方样条函数拟合NO₂长期暴露与IS患者死亡风险的暴露-反应关系。通过纳入NO₂与归一化差异植被指数水平的交互项探究绿地暴露的效应修饰作用。最后进行了一系列敏感性分析，并基于不同性别、年龄组以及城乡进行了亚组分析。结果 研究共包含46 252名IS患者，4个区（县）2013―2019年NO₂的年平均浓度为（43.30±1.32）μg/m³。研究显示，NO₂每升高1个IQR,IS患者死亡的HR值（95%CI）为1.22（1.15～1.29）。暴露-反应关系显示NO₂长期暴露与IS患者的死亡风险呈非线性关系(P_非线性<0.001)。交互作用结果发现NO₂与绿地暴露之间存在交互作用(P_非线性=0.005)，且NO₂对IS患者死亡的影响在绿地暴露程度较高的地区最弱（HR=1.19,95%CI:1.12～1.26,P<0.001）。不同性别、不同年龄组以及农村地区，同样发现NO₂长期暴露与绿地暴露存在交互作用（均P<0.05）。结论 NO₂长期暴露是IS患者死亡风险的危险因素，且绿地暴露可能缓解这种危害效应。更多还原

【Abstract】 Objective This study aimed to investigate the association between long-term nitrogen dioxide （NO₂） exposure and the risk of death in ischemic stroke （ischemic stroke,IS） patients,as well as the modification of greenness on this association.Methods We conducted a longitudinal study on IS cases in 4 districts/counties in the northwest region of Shandong Province with relatively high NO₂concentrations from 2013 to 2019.Participants were followed up until December 31,2019,or the date of death.A time-dependent Cox proportional risk model was used to assess the hazard ratio （HR） and its95%CIfor stroke-related death in IS patients perIQRincrease in NO₂.The exposure-response relationship between long-term NO₂exposure and the risk of IS patient mortality was fitted using a restricted cubic spline function.We then explored the effect modification role of greenness exposure by incorporating an interaction term between NO₂and normalized difference vegetation index （NDVI） levels.Finally,we conducted a series of sensitivity analyses and subgroup analyses based on different genders,age groups,and urban/rural areas.Results A total of 46 252 IS patients were included in the study and the annual mean concentration of NO₂in the 4 districts/counties from 2013 to 2019 was （43.30±1.32）μg/m³.The results showed that the HR of death in IS patients were 1.22 （1.15-1.29） for eachIQRincrease in NO₂.The exposure-response relationship showed a non-linear relationship between long-term NO₂exposure and the risk of IS patient mortality.The results of the interaction were found to be statistically significant (P_nolinear=0.005) withHRsof 1.23 （1.17-1.30）,1.21 （1.15-1.28）,and 1.19 （1.12-1.26） for eachIQRof NO₂rise in patients with IS at the low,middle,and high levels of exposure to the greenness,respectively.Interaction effects between long-term NO₂exposure and greenness exposure was found across different gender and age groups,as well as in rural areas （allP<0.05）.Conclusions Long-term exposure to NO₂is considered a risk factor for mortality in IS patients,while greenness may potentially mitigate this detrimental effect.更多还原