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

doi:10.16462/j.cnki.zhjbkz.2024.05.010

文章导航 > 中华疾病控制杂志 > 2024 > 28(5): 554-560

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:

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

引用本文:

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

赵珂¹,
胡杨¹,
张珮瑶¹,
刘超¹,
刘成榕¹,
师春香²,
韦晶³,
张丙银⁴,
鹿子龙⁴,
郭晓雷⁴,
薛付忠^{5, 6},
贾贤杰^{1, 5, 6},
芈静^1, ,

1.
蚌埠医学院公共卫生学院流行病与卫生统计学教研室，蚌埠 233030
2.
国家气象信息中心，北京 100081
3.
马里兰大学大气与海洋科学系地球系统科学交叉研究中心，美国大学公园市 20742
4.
山东省疾病预防控制中心慢性非传染性疾病防制所，济南 250014
5.
山东大学齐鲁医学院公共卫生学院生物统计学系，济南 250012
6.
国家健康医疗大数据研究院，济南 250003

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
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- 被引次数: 0
出版历程
- 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

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

1.
Department of Epidemiology and Statistics, School of Public Health, Bengbu Medical University, Bengbu 233030, China
2.
National Meteorological Information Center, Beijing 100081, China
3.
Department of Atmospheric and Oceanic Sciences, Earth System Sciences Interdisciplinary Center, University of Maryland, City of College Park 20742, U.S.A
4.
Department for Chronic and Non-communicable Diseases Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan 250014, China
5.
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
6.
National Institute of Health Data Science of China, Jinan 250003, China

Funds:

Natural Science Research Projects in Anhui Universities KJ2021A0710

Graduate Student Innovation Program Projects Byycx22072

More Information

Corresponding author: MI Jing, E-mail: mijing@bbmc.edu.cn

摘要

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。
- 缺血性脑卒中 /
- 二氧化氮 /
- 绿地暴露 /
- 纵向研究
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 NO₂ concentrations 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 its 95% CI for stroke-related death in IS patients per IQR increase in NO₂. The exposure-response relationship between long-term NO₂ exposure 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 NO₂ and 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 NO₂ in 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 each IQR increase in NO₂. The exposure-response relationship showed a non-linear relationship between long-term NO₂ exposure and the risk of IS patient mortality. The results of the interaction were found to be statistically significant (P_nolinear=0.005) with HRs of 1.23 (1.17-1.30), 1.21 (1.15-1.28), and 1.19 (1.12-1.26) for each IQR of NO₂ rise in patients with IS at the low, middle, and high levels of exposure to the greenness, respectively. Interaction effects between long-term NO₂ exposure and greenness exposure was found across different gender and age groups, as well as in rural areas (all P < 0.05). Conclusions Long-term exposure to NO₂ is considered a risk factor for mortality in IS patients, while greenness may potentially mitigate this detrimental effect.
- Ischemic stroke /
- Nitrogen dioxide /
- Greenness /
- Longitudinal study

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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.

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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.

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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^① Variable^①	NO₂暴露水平 ^② NO₂ exposure levels ^②			H/χ²值 value	P值 value
变量^① Variable^①	T1组group (n=15 262)	T2组group (n=15 725)	T3组group (n=15 265)	H/χ²值 value	P值 value
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(P₂₅，P₇₅)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(P₂₅，P₇₅); 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).

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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
年份 Year		P₂₅	P₅₀	P₇₅		NO₂暴露水平/ (μg·m^-3), x±s NO₂ exposure levels/(μg·m^-3), x±s
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.

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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 ^④ NDVI levels ^④			P值 value
模型Models	总体Total	低Low (＜0.38)	中等Middle (0.38~0.56)	高High (＞0.56)	P值 value
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 ^① Sensitivity analysis ^①	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 ^② Sensitivity analysis ^②	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 ^③ Sensitivity analysis ^③	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PM_2.5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 PM_2.5 and O₃ based on multifactor model; ③ all-cause mortality as the outcome event of interest for the study.

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