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二氧化氮长期暴露与缺血性脑卒中患者死亡的关联及绿地暴露的效应修饰研究

赵珂 胡杨 张珮瑶 刘超 刘成榕 师春香 韦晶 张丙银 鹿子龙 郭晓雷 薛付忠 贾贤杰 芈静

赵珂, 胡杨, 张珮瑶, 刘超, 刘成榕, 师春香, 韦晶, 张丙银, 鹿子龙, 郭晓雷, 薛付忠, 贾贤杰, 芈静. 二氧化氮长期暴露与缺血性脑卒中患者死亡的关联及绿地暴露的效应修饰研究[J]. 中华疾病控制杂志, 2024, 28(5): 554-560. doi: 10.16462/j.cnki.zhjbkz.2024.05.010
引用本文: 赵珂, 胡杨, 张珮瑶, 刘超, 刘成榕, 师春香, 韦晶, 张丙银, 鹿子龙, 郭晓雷, 薛付忠, 贾贤杰, 芈静. 二氧化氮长期暴露与缺血性脑卒中患者死亡的关联及绿地暴露的效应修饰研究[J]. 中华疾病控制杂志, 2024, 28(5): 554-560. doi: 10.16462/j.cnki.zhjbkz.2024.05.010
ZHAO Ke, HU Yang, ZHANG Peiyao, LIU Chao, LIU Chengrong, SHI Chunxiang, WEI Jing, ZHANG Bingyin, LU Zilong, GUO Xiaolei, XUE Fuzhong, JIA Xianjie, MI Jing. Association of long-term nitrogen dioxide exposure with death in ischemic stroke patients and effect modification of greenness[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2024, 28(5): 554-560. doi: 10.16462/j.cnki.zhjbkz.2024.05.010
Citation: ZHAO Ke, HU Yang, ZHANG Peiyao, LIU Chao, LIU Chengrong, SHI Chunxiang, WEI Jing, ZHANG Bingyin, LU Zilong, GUO Xiaolei, XUE Fuzhong, JIA Xianjie, MI Jing. Association of long-term nitrogen dioxide exposure with death in ischemic stroke patients and effect modification of greenness[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2024, 28(5): 554-560. doi: 10.16462/j.cnki.zhjbkz.2024.05.010

二氧化氮长期暴露与缺血性脑卒中患者死亡的关联及绿地暴露的效应修饰研究

doi: 10.16462/j.cnki.zhjbkz.2024.05.010
基金项目: 

安徽高校自然科学研究项目 KJ2021A0710

研究生创新计划项目 Byycx22072

详细信息
    通讯作者:

    芈静,E-mail: mijing@bbmc.edu.cn

  • 中图分类号: R181

Association of long-term nitrogen dioxide exposure with death in ischemic stroke patients and effect modification of greenness

Funds: 

Natural Science Research Projects in Anhui Universities KJ2021A0710

Graduate Student Innovation Program Projects Byycx22072

More Information
  • 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。
  • 图  1  NO2长期暴露与IS患者死亡风险的暴露-反应关系

    NO2:二氧化氮;IS:缺血性脑卒中。

    Figure  1.  Exposure-response relationship between long-term exposure to NO2 and risk of death in patients with ischemic stroke

    NO2: nitrogen dioxide; IS: ischemic stroke.

    图  2  不同特征人群中NDVI对二氧化氮与缺血性脑卒中患者死亡关联的修饰效应

    NDVI: 归一化差异植被指数。

    Figure  2.  Modifying effects of NDVI on the association between nitrogen dioxide and death in ischemic stroke patients in different characteristic populations

    NDVI: normalized difference vegetation index.

    表  1  NO2暴露水平三分位数组人群基线特征的比较

    Table  1.   Comparison of baseline characteristics of populations in three quartiles of NO2 exposure levels

    变量 Variable NO2暴露水平 NO2 exposure levels H/χ2
    value
    P
    value
    T1组group (n=15 262) T2组group (n=15 725) T3组group (n=15 265)
    年龄/岁Age/years 67(60~74) 67(60~74) 67(59~74) 3.76 0.152
    性别Gender 22.36 <0.001
      男Male 8 386(54.95) 8 372(53.24) 7 981(52.28)
      女Female 6 876(45.05) 7 353(46.76) 7 284(47.72)
    城乡Urban and rural 2 677.60 <0.001
      城市Urban 4 697(30.78) 6 069(38.59) 9 026(59.13)
      农村Rural 10 565(69.22) 9 656(61.41) 6 239(40.87)
    人口密度/(人·千米-2) Population density/(persons·km-2) 482.88(339.59~826.77) 486.17(336.31~894.44) 655.14(348.77~1 188.61) 520.69 <0.001
    道路密度/(km·km-2) Road density/(km·km-2) 1.88(1.30~3.04) 2.27(1.35~3.81) 2.57(1.66~5.58) 2 056.50 <0.001
    平均温度/℃ Average temperature/℃ 15.67(15.56~15.86) 15.44(15.27~15.62) 15.33(15.17~15.38) 17 707.00 <0.001
    相对湿度/% Relative humidity /% 65.73(64.24~67.91) 68.88(65.71~69.50) 68.54(68.01~69.04) 8 321.10 <0.001
    降水量/mm Rainfall/mm 0.71(0.65~0.79) 0.87(0.75~0.93) 1.00(0.89~1.17) 19 167.00 <0.001
    病床数/1 000人-1 Number of hospital beds/1 000 persons-1 3.55(2.99~3.55) 2.99(2.71~3.55) 2.71(2.71~2.71) 15 741.00 <0.001
    初等教育人数/1 000人-1 Number of primary education/1 000 persons-1 73.60(69.21~73.60) 69.21(61.34~73.60) 61.34(61.34~61.34) 15 741.00 <0.001
    人年均GDP/元Annual GDP per capita/yuan 48 589.88(36 326.80~48 589.88) 72 456.57(48 589.88~76 539.74) 76 539.74(76 539.74~76 539.74) 18 012.00 <0.001
    NDVI水平NDVI levels 7 458.50 <0.001
      低Low 1 253(8.21) 3 817(24.27) 5 360(35.11)
      中Middle 6 895(45.18) 6 436(40.93) 8 923(58.45)
      高High 7 114(46.61) 5 472(34.80) 982(6.44)
    注:NO2,二氧化氮;NDVI,归一化差异植被指数;GDP,国内生产总值。
    ①以人数(占比/%)或M(P25P75)表示;② NO2暴露水平按照三分位数分为3组:T1组(≤40.16 μg/m3),T2组(>40.16~<41.96 μg/m3),T3组(≥41.96 μg/m3)。
    Note: NO2, nitrogen dioxide; NDVI, normalized difference vegetation index; GDP, gross domestic product.
    ① Number of people (proportion/%) or M(P25P75); ② NO2 exposure levels were divided into 3 groups according to tertiles : T1 group(≤40.16 μg/m3), T2 group(>40.16-<41.96 μg/m3), T3 group(≥41.96 μg/m3).
    下载: 导出CSV

    表  2  2013―2019年NO2暴露水平的时间变化

    Table  2.   Temporal changes in NO2 exposure levels from 2013-2019

    年份
    Year
    NO2暴露水平最小值/(μg·m-3)
    Minimum value of NO2 exposure levels/(μg·m-3)
    NO2暴露水平四分位数/(μg·m-3)
    Quartile of NO2 exposure levels/(μg·m-3)
    NO2暴露水平最大值/(μg·m-3)
    Maximum values of NO2 exposure levels/(μg·m-3)
    NO2暴露水平/ (μg·m-3), x±s
    NO2 exposure levels/(μg·m-3), x±s
    P25 P50 P75
    2013 43.05 48.41 50.62 51.34 56.92 49.77±2.75
    2014 41.14 45.91 46.53 48.23 54.14 46.84±2.38
    2015 38.84 41.44 42.99 44.52 48.54 43.15±2.04
    2016 35.74 38.75 40.79 42.83 44.74 40.70±2.39
    2017 39.19 40.38 40.94 41.93 44.63 41.25±1.34
    2018 37.70 39.06 39.59 40.19 41.97 39.65±0.85
    2019 37.77 39.74 40.86 44.17 45.33 41.70±2.40
    均值Mean 40.29 42.44 43.38 43.74 47.85 43.30±1.32
    注:NO2,二氧化氮。
    Note: NO2, nitrogen dioxide.
    下载: 导出CSV

    表  3  NO2长期暴露与IS患者死亡风险的关联及与NDVI的修饰作用

    Table  3.   Association of long-term NO2 exposure with the risk of death in patients with ischemic stroke and the modifying effect with NDVI

    模型Models 总体Total NDVI水平 NDVI levels P
    value
    低Low
    (<0.38)
    中等Middle
    (0.38~0.56)
    高High
    (>0.56)
    死亡人数Number of deaths 3 729 838 1 879 1 012
    人年数Person-years 105 423.80 26 284.30 53 534.63 25 604.83
    单因素模型Single-factor model 1.07(1.02~1.11) 1.08(1.04~1.13) 1.10(1.05~1.15) 1.11(1.06~1.16) <0.001
    多因素模型Multifactorial model 1.22(1.15~1.29) 1.23(1.17~1.30) 1.21(1.15~1.28) 1.19(1.12~1.26) <0.001
    敏感性分析 Sensitivity analysis 1.02(0.97~1.07) 1.03(0.98~1.08) 1.01(0.96~1.07) 0.99(0.94~1.04) <0.001
    敏感性分析 Sensitivity analysis 1.12(1.04~1.20) 1.12(1.04~1.20) 1.09(1.02~1.18) 1.07(1.00~1.16) <0.001
    敏感性分析 Sensitivity analysis 1.07(1.02~1.11) 1.08(1.03~1.12) 1.06(1.01~1.11) 1.03(0.99~1.08) <0.001
    注:1. NO2,二氧化氮;IS,缺血性脑卒中;NDVI, 归一化差异植被指数。
    2. 模型均以NO2每增加IQR形式纳入,IQR=3.77 μg/m3。单因素模型无调整;多因素模型调整人口密度、道路密度、病床数、初等教育人口数、人均GDP、年平均温度、相对湿度、降水量和城乡;模型均按性别和年龄组联合分层。
    ① NO2暴露匹配使用滞后一年的移动平均值暴露;②在多因素模型的基础上进一步调整了PM2.5和O3; ③以全因死亡作为研究关注的结局事件。
    Note: 1. NO2, nitrogen dioxide; IS, ischemic stroke; NDVI, normalized difference vegetation index.
    2. Models were included in the form of IQR per increase in NO2, IQR=3.77 μg/m3. No adjustments to the single-factor mode; multifactorial model adjusted for population density、road density、number of hospital beds、number of primary education、GDP per capital、average temperature、relative humidity、rainfall and urban/rural; models were all stratified by sex and age group.
    ① NO2 exposure matching used moving average exposures lagged by one year; ② further adjustment of PM2.5 and O3 based on multifactor model; ③ all-cause mortality as the outcome event of interest for the study.
    下载: 导出CSV
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  • 收稿日期:  2023-06-28
  • 修回日期:  2023-10-30
  • 网络出版日期:  2024-06-05
  • 刊出日期:  2024-05-10

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