目的  中国脑卒中患者人数呈上升趋势，而环境危险因素对该疾病发展的影响缺乏综合性概述。本研究旨在探讨影响脑卒中的环境危险因素，为决策者制定卫生政策和干预措施提供依据。

方法  检索中国知网、万方、维普、PubMed、Web of Science、Scopus数据库有关中国脑卒中环境危险因素的文献，检索时限为2012年1月至 2022 年 5 月。对环境危险因素的种类、频次进行描述性分析，对脑卒中与环境因素之间的关系进行叙述性分析。

结果  初检共获取文献12 774篇，最终纳入文献215篇，涉及8类43种环境因素。研究最多的因素是气象因素（52.56%），其次是空气污染（47.44%）；最常报告的指标分别是气温（40.47%）和PM_2.5（28.37%）。气象因素中，涉及气温的大部分研究提示其是脑卒中发生的影响因素，并发现脑卒中及其亚型存在季节性，近一半的研究发现较高的气压与较高的脑卒中及其亚型发生风险相关。对于空气污染，研究发现较高水平的PM_2.5、PM₁₀、CO、NO₂、O₃、SO₂与较高的脑卒中发生风险相关。此外，燃料暴露、被动吸烟也与脑卒中风险增加相关。

结论  环境因素对中国人群脑卒中发生风险具有一定程度的影响，需进一步的研究评估这些关联，阐明涉及的具体机制，并探索更多的环境因素对脑卒中的潜在影响。

脑卒中已成为全球日益关注的慢性非传染性疾病。根据全球疾病、伤害和危险因素负担研究（GBD 2019）报告，2019年，有1 220万脑卒中新发病例，1.01亿脑卒中现患病例，1.43亿因脑卒中导致的伤残调整寿命年（DALYs)，655万例脑卒中死亡病例[1]。在全球范围内，脑卒中仍是2019年第二大死亡原因（占总数的11.6%）和第三大死亡及残疾的原因（占总DALYs的5.7%），也是中国患者的主要死亡原因之一[1-2]。中国是世界上最大的发展中国家，人口约占世界总人口数的五分之一。虽然从1990年到2019年，中国脑卒中的发病率和死亡率有所下降，但新发病例数和死亡人数几乎翻了一倍，现患病例人数于2019年居世界首位[1, 3]。脑卒中的年轻化趋势越来越明显，研究表明在70岁以下的人群中，患病率增加了22.0%，发病率增加了15.0%[1]。卒中后在1个月内病死率约为15%，1年内为25%，5年内为50%[4]，对人群的健康构成了巨大威胁，因此有必要控制影响脑卒中发病率的危险因素。除了高血压、糖尿病、高脂血症等传统危险因素外，空气污染、气象因素等环境危险因素也越来越受到研究者的关注[5-7]。作为人群日常生活的载体，环境中的各种因素影响着我们的生活和健康。通过控制环境因素对人体的影响从而降低脑卒中的发病率，是三级预防的手段之一。近年来，中国脑卒中环境危险因素研究呈持续增长趋势[8-13]，但缺乏对脑卒中环境危险因素进行系统地梳理。据此，本文通过综合近十年中国脑卒中环境危险因素研究，了解中国脑卒中环境危险因素的研究现状，确定环境因素与脑卒中之间的关系，为决策者制定卫生政策和干预措施提供参考。

1 资料与方法

1.1 纳入与排除标准

纳入标准：①至少一种环境因素作为主要研究变量，并评估其与脑卒中的相关性；②研究对象为脑卒中患者，脑卒中的病理亚型分为缺血性脑卒中（脑、视网膜和脊髓梗死）与出血性脑卒中（脑内出血和蛛网膜下腔出血）[14]；③研究结局为脑卒中发病、死亡或寿命损失年（YLL）；④研究类型为观察性研究，包括横断面研究、生态学研究、病例对照研究、病例交叉研究或队列研究等 ；⑤研究地点为中国 ；⑥以中文或英文出版。

排除标准：①研究对象为其他特定疾病人群，如在糖尿病人群中的研究；②个案调查、病例报告、会议论文、学位论文、社论/函件、综述、Meta分析；③未经任何统计推断的研究；④重复研究；⑤无法获得全文的研究。

1.2 检索策略

检索数据库包括中国知网（CNKI）、万方数字化期刊全文数据库、维普中文期刊数据库、PubMed、Web of Science 和Scopus。检索文章发表时段为2012年1月至2022 年5月。采用主题词和自由词相结合的检索方式，检索字段为标题、摘要、关键词或主题，根据不同数据库进行调整。中文检索词为卒中、中风、脑血管意外、脑出血、脑梗死、脑梗塞、蛛网膜下腔出血、环境因素、环境污染、空气污染、大气污染、一氧化碳、二氧化硫、二氧化氮、臭氧、颗粒物、PM_2.5、PM₁₀、气象、气候、季节、天气、气温、温度、气压、湿度、风速。英文检索词为stroke、cerebrovascular accident、brain vascular accident、cerebrovascular disease、cerebrovascular disorder、cerebral haemorrhage、cerebral infarction、subarachnoid haemorrhage、environment、environmental、air pollution、air pollutants、carbon monoxide、sulphur dioxide、nitrogen dioxide、ozone、particulate matter、PM_2.5、PM₁₀、meteorology、meteorologic、weather、climate、season、temperature、atmospheric pressure、air pressures、humidity、wind、China。以PubMed为例，具体检索策略见框1。

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  框图1 PubMed检索策略

  Box1.PubMed search strategy

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1.3 文献筛选、资料提取与纳入研究的偏倚风险评价

由2名研究者独立对获得的文献进行筛选、提取资料并交叉核对，如遇分歧，讨论或咨询第三方解决。将检索到的文献导入NoteExpress V3.5.0软件和Endnote X9.1软件，根据标题、摘要排除明显不符合纳入标准的文献，下载并阅读全文后确定最终纳入文献。资料提取内容包括作者、发表年份、研究地点、研究时间、研究设计、统计学方法、环境危险因素、卒中分型、疾病结局、效应估计。2 名研究者采用美国卫生保健质量和研究机构（AHRQ）横断面研究评价量表和纽卡斯尔 - 渥太华量表（NOS）评价纳入研究的偏倚风险，并交叉核对结果。

1.4 统计学分析

应用 Excel 2019建立文献数据库，使用频次、频率对脑卒中类型、环境危险因素、研究设计、统计学方法和效应估计进行描述性分析。对纳入研究的主要结果进行叙述性综合。

2 结果

2.1 文献筛选流程及结果

初检共获得文献12 774篇，经逐层筛选最终纳入文献215篇，其中81篇以中文发表，134篇以英文发表。文献筛选流程见图1。

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  图1 文献筛选流程

  Figure1.Flow chart of study selection

  注：*检索的数据库及检出文献数具体为知网（n=2 884）、万方（n=4 410）、维普（n=3 631）、PubMed（n=307）、Web of Sciense（n=790）、Scopus（n=752）

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2.2 纳入研究的基本特征及偏倚风险评价

研究的疾病类型占比接近，研究最多的疾病结局为发病（67.44%）。在纳入的215项研究中，一共报告了8类43种环境危险因素，其中研究最多的环境因素是气象因素（52.56%），其次是空气污染（47.44%）。在气象因素和空气污染类别下，研究最多的环境因素分别是气温（40.47%）和PM_2.5（28.37%），详见表1。纳入研究的AHRQ量表得分为4~10分，NOS得分为7~9分，纳入研究的基本特征和偏倚风险评价结果详见表2。

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  表格1 脑卒中类型、疾病结局、环境危险因素的研究数量分布情况

  Table1.The number of studies addressing each subtopic of the domains: stroke types, disease outcome and environmental risk factors

  注：#其他包括居住环境、居住海拔、热气候指数（UTCI）、被动吸烟；*气象因素与空气污染为“环境危险因素”的亚组

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  表格2 纳入研究的基本特征

  Table2.Key characteristics of studies included in the systematic review

  注：EF：超额死亡率；API：空气污染指数；NDVI：归一化植被指数；UTCI：热气候指数

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表3总结了脑卒中环境危险因素研究的特点，包括研究设计、统计学方法和效应估计。大多数研究设计为生态学研究（66.05%），广义相加模型（GAM）是使用最多的统计学方法（27.44%），相对危险度（RR）是报告最多的效应估计指标（32.56%）。

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  表格3 研究设计、统计学方法、效应估计指标总结

  Table3.Summary of study design, statistical methods, effect measures

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2.3 脑卒中与环境危险因素的关联

脑卒中及其亚型与环境危险因素之间相关性统计学显著的文献数与相关性统计学（部分）不显著的文献数分布见表4。

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  表格4 脑卒中及其亚型与环境危险因素的关联总结

  Table4.Summary of the relationship between stroke and its subtypes with environmental risk factors

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2.3.1 气象因素

共计113项研究探讨了各种气象因素与脑卒中之间的关联[10-13, 15-123]，其中87项研究涉及气温，且大部分研究均发现了统计学关联。以下就主要的3个气温指标进行叙述。

共有37项研究涉及日均气温。在21项涉及日均气温与缺血性脑卒中的研究中，11项研究发现非线性关联[15, 22, 36, 80-81, 89-90, 108, 110, 113, 120]，1项研究发现正相关[11]，1项研究发现负相关[30]，2项研究发现统计学关联[24, 69]。在21项涉及日均气温与出血性脑卒中的研究中，11项研究发现非线性关联[15, 36, 44, 80-81, 89-90, 108, 110, 113, 124]，7项研究发现负相关[27, 32, 49, 58, 75, 107, 116]，1项研究发现统计学关联[24]。在15项涉及日均气温与脑卒中的研究中，12项研究发现非线性关联[15, 18, 35, 80-81, 88, 96-97, 110, 117-118, 122]，1项研究发现负相关[70]，1项研究发现氮氧化物和温度对脑卒中死亡率有交互作用[85]。

25项研究涉及极端气温，包括寒潮、热浪或各种定义的高温、低温。在13项涉及极端气温与缺血性脑卒中的研究中，1项研究发现非线性关联[103]，4项研究发现高温、低温暴露均是缺血性脑卒中危险因素[26, 80, 90, 110]，4项研究发现高温暴露是缺血性脑卒中危险因素[89, 104, 111, 114]，3项研究发现低温暴露是缺血性脑卒中危险因素[102, 108, 113]。在12项涉及极端气温与出血性脑卒中的研究中，1项研究发现非线性关联[103]，3项研究发现高温、低温暴露均是出血性脑卒中危险因素[44, 90, 110]，1项研究发现高温暴露是出血性脑卒中危险因素[111]，3项研究发现低温暴露是出血性脑卒中危险因素[108, 113-114]，2项研究发现高温暴露、低温暴露分别是出血性脑卒中的保护因素、危险因素[84, 89]。在16项涉及极端气温与脑卒中的研究中，1项研究发现非线性关联[103]，7项研究发现高温、低温暴露均是脑卒中危险因素[25, 35, 83, 110, 112, 117, 122]，6项研究发现高温暴露是脑卒中危险因素[38, 52, 98, 104, 111, 115]，2项研究发现低温暴露是脑卒中危险因素[80, 96]。

24项研究涉及温度变异指标。在11项涉及温度变异相关指标与缺血性脑卒中的研究中，2项研究发现非线性关联[92, 95]，4项研究发现其为缺血性脑卒中危险因素[11, 91, 99, 114]，1项研究发现负相关[33]，1项研究发现统计学关联[24]。在9项涉及温度变异相关指标与出血性脑卒中的研究中，1项研究发现非线性关联[95]，3项研究发现其为出血性脑卒中危险因素[75, 94, 114]，1项研究发现负相关[76]，1项研究发现统计学关联[24]。在11项涉及温度变异相关指标与脑卒中的研究中，5项研究发现非线性关联[12, 82, 87, 95, 101]，4项研究发现其为脑卒中危险因素[86, 105-106, 119]，1项研究发现负相关[57]。

33项研究涉及脑卒中及其亚型的季节性，尽管研究结果不同，但绝大多数研究发现脑卒中及其亚型是存在季节性的。出血性脑卒中的季节性研究中，24项研究存在统计学相关，其中10项研究发现冬季高发[37, 41-42, 47, 59-60, 64, 71, 74, 121]。关于气压，只有不到一半的研究发现了相关性，且绝大部分为正相关。部分研究涉及湿度、风速、降雨和日照时数，但影响证据较低。关于水汽压，1项研究发现脑梗死的发病与同节气的平均水汽压呈正相关，同时前一节气的平均水汽压与脑梗死发病呈正相关[61]，1项研究发现水汽压与缺血性、出血性脑卒中风险均呈正相关[107]。关于风向，1项研究发现脑出血发病在不同风向时分布不均匀[32]。关于蒸发量、舒适度指数对脑卒中及其亚型的影响的研究数量非常有限，但发现了部分统计学关联，而涉及低云量、紫外线强度的研究中未发现关联。

2.3.2 空气污染

102项研究调查了各种空气污染与脑卒中及其亚型风险之间的关联[8-9, 18, 28, 33, 66, 70, 84-85,107,124-215]。对于颗粒物，大部分研究结果发现较高浓度的PM_2.5、PM₁₀、PM₁与较高的缺血性脑卒中和脑卒中风险相关，较高浓度的PM_2.5-10与较高的缺血性脑卒中风险相关，但各有1项研究发现PM₁₀、PM₁浓度与出血性脑卒中风险呈负相关[107, 143]，尚未发现PM_1-2.5对脑卒中及其亚型的影响。

对于气态污染物，本研究也发现较高浓度的NO₂、O₃与较高的脑卒中及其亚型风险相关，但各有1项研究发现NO₂、O₃浓度与出血性脑卒中风险呈负相关[33, 198]。同时，研究还发现较高浓度的SO₂、CO对缺血性脑卒中和脑卒中存在不利影响，仅各有1项研究发现SO₂、CO浓度与缺血性脑卒中风险呈负相关[28, 140]，1项研究发现CO浓度与脑卒中风险呈负相关[211]。关于Ox，1项研究表明大气氧化性污染物暴露可引起脑卒中死亡风险升高，未发现高温与高浓度大气氧化性污染物对脑卒中死亡风险存在交互作用[18]。关于NO的一项研究表明它和温度对卒中死亡率有交互作用[85]。对NOx和区域空气污染的研究有限，有部分证据表明其增加脑卒中及其亚型的发生风险。尚未发现空气污染指数、交通空气污染、空气质量对脑卒中及其亚型的影响。

2.3.3 其他环境因素

极少数研究调查了燃料暴露、城市环境特征、居住环境、居住海拔、热气候指数和被动吸烟。对于燃料暴露，3项研究均发现使用固体燃料与脑卒中风险增加有关[216-218]，1项研究发现使用无烟煤可能与脑卒中的死亡率增加有关[219]。对于城市环境特征，1项研究发现高密度居住环境与脑卒中风险增加有关[220]，1项研究发现高夜间地表温度值和不透水地表比例可能加剧热对脑卒中发病的影响、高归一化植被指数值和水体比例可能缓解热的有害影响[221]，暂未发现开放空间、绿化、白天地表温度值对脑卒中及其亚型的影响[84, 221]。除此之外，1项研究发现出血性脑卒中发病率与热气候指数呈负相关[107]，1项研究发现被动吸烟与各种类型的脑卒中的死亡有关[222]，暂未发现居住环境、居住海拔对脑卒中及其亚型的影响[223]。

3 讨论

本文共纳入215项研究，旨在总结我国研究报告的脑卒中环境危险因素种类、环境因素与脑卒中的关联。研究发现，与中国地区脑卒中相关最常见的环境因素是气象因素和空气污染。

在气象因素中，最常报告的因素是气温。本研究发现气温与脑卒中及其亚型的关联是显著的。关于气温的研究聚焦于日均气温与脑卒中的非线性关联，以及极端气温、温度变异指标对脑卒中的不利影响，并且这些关联大部分是显著的。表明脑卒中风险与气温有紧密的联系，但温度对脑卒中及其亚型的影响不完全一致，这与许多研究的发现是一致的[224-226]。环境温度增加脑卒中风险的机制在冷或热温度暴露中有所不同。在低温暴露下，它主要与交感神经活动增加有关，导致血压升高、外周血管收缩、血小板计数增加和血液黏度增加[227]。高温暴露导致脑卒中风险增加的机制是出汗和皮肤血流量增加、产生脱水、血液黏度增加、血液浓度增加和胆固醇水平升高等[228]。而温度变化导致的脑卒中风险增加可能是不稳定的温度改变心率、血液胆固醇水平、血压、血浆纤维蛋白原浓度、血小板黏度，并增加血液中的炎症因子，而这些变化可能会加剧心脑血管疾病患者的疾病状况[106]。关于季节，绝大多数研究中脑卒中及其亚型的发病和死亡等风险存在季节性，但季节分布的结果并不一致，可能与不同地区的季节变化和不同研究人群的人口学特征有关。实际上，脑卒中风险随季节而变化的机制尚不完全清楚，有研究认为适应天气的生理过程的变化可能会触发脑卒中的发生[229]。此外，寒冷的气候可能会改变人类活动，如室内吸烟、剧烈活动和饮酒量增加，而这些是冬季出血性脑卒中发生风险的常见原因[230]。较高的气压可能是脑卒中及其亚型的危险因素。研究表明，大气压的影响机制可能是通过触发内源性炎症和改变内皮功能直接影响血管壁[231-232]，也可能通过对动脉粥样硬化斑块施加应力导致斑块破裂[233]。

本研究发现，暴露在较高空气污染水平下发生脑卒中的风险较高，尤其是PM_2.5、PM₁₀、CO、NO₂、O₃和SO₂，但这些空气污染暴露对出血性脑卒中的影响较低，这与最近的综述和Meta分析的研究结果相似[234-236]。PM₁、PM_2.5-10与脑卒中的关联有待进一步分析。研究表明，空气污染暴露促进全身血管氧化应激反应，随后内皮细胞功能障碍、单核细胞活化和一些致动脉粥样硬化的脂蛋白改变[237]。此外，由于凝血因子和血小板活化的增加，空气污染更有利于血栓的形成[238]。纵使空气污染的风险很小，鉴于大量人口可能暴露在污染中，受影响的人口可能达到较高的比例，应对空气污染和气象要素等环境因素进行监管和监测，确定缓解措施，有助于避免人口过度暴露于大气中的有害成分和非舒适的环境中。

本研究发现燃料暴露、被动吸烟对脑卒中有危险影响。尽管这些研究的证据很少，鉴于几项研究中一致的相关性，应采取行动减少这些环境危险因素的暴露。生物质（木材、作物残渣）和煤炭是中国某些农村地区经常使用的燃料，这些燃料通常在通风不良的空间内燃烧，而低热的炉灶通常会排放颗粒物（PM）、多环芳烃（PAHs）、重金属和许多其他有机污染物的复杂污染物混合物[217, 239]，这些污染物与环境污染有关，而且颗粒物暴露是脑卒中的危险因素。关于城市环境特征的研究较少，需要更多的研究来了解这些特征与脑卒中之间的关系。

未来仍需开展更多高质量的研究来证实现有证据，并了解环境在脑卒中预防中的作用。此外，评估多个相关的环境决定因素将有助于确定脑卒中预防的关键决定因素，从而为政策决策提供有效的信息。本文纳入的研究中涉及交互作用的研究有限，研究环境特征之间的相互作用是一个可探索的方向。同样，需要更清楚地阐明环境对脑卒中的影响机制。由于脑卒中导致的极大的疾病负担，迫切需要开展的研究关注弱势群体和农村人口。最后，本研究纳入的是在中国进行的研究，将本研究结果与全球其他地区的研究进行比较，可以观察到更多的环境危险因素，从而对脑卒中的其他未研究特征进行更多分析，例如噪声、食品污染、辐射、磁场、光污染等[240-242]。

本研究存在一定局限性。首先，本研究仅对发表文献进行综述，未纳入会议摘要或未发表的文献等，可能存在发表偏倚。其次，由于研究类型的广泛性和这些风险因素的评估和分析方法上存在异质性，本系统评价未进行Meta分析。未来仍需进一步的研究来验证这些环境因素与脑卒中的关系。

本研究是我国最新的关于脑卒中环境危险因素的系统评价。研究表明环境因素对我国地区脑卒中发生风险有一定程度的影响。极端气温、温度变异和较高水平的PM_2.5、PM₁₀、CO、NO₂、O₃、SO₂、燃料暴露、被动吸烟与较高的脑卒中及其亚型发生风险相关，其中有少数空气污染物与出血性脑卒中的关联证据相对较低。冬季可能与较高的出血性脑卒中风险相关。现有的其他气象因素和空气污染、城市环境特征、热气候指数的研究结果参差不齐，且部分环境因素的研究很少。最后，环境影响脑卒中风险的机制尚不清楚。需要进一步的研究来评估这些关联并阐明所涉及的具体机制，并探索更多的环境因素对脑卒中的潜在影响。

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