The Association Between Ambient Air Pollution And Stroke

Backgrounds and objectivesAir pollution,as an important risk factor for non-communicable diseases,has become a serious public health problem worldwide and could lead to 7 million premature deaths every year.Previous studies have shown that air pollution has a significant adverse health effect on total mortality,respiratory and cardiovascular diseases.Compared with developed countries and regions with lower exposure levels of air pollution,China suffered a greater burden of disease from air pollution.However,the effect of air pollution is not consistent in China and we still lack of data on the adverse health effects of air pollution in different regions and different populations.Stroke is a disorder in which insufficient blood flow to the brain or impaired blood circulation to the brain tissue results in a loss of local neurological function.In addition to its serious sequelae,stroke also brings a huge burden of disease to the patients with their families and the society.Stroke has become the disease with the highest annual loss of disability-adjusted life years（DALYs）in China.Previous studies have suggested that compared with hypertension,the risk of stroke in low-and middle-income countries may be more attributed to air pollution.And from the perspective of public health,air pollution is also one of the most common and modified risk factors for stroke.However,current epidemiological studies on the association between air pollution and stroke still have some limitations.Firstly,a large number of studies have only focused on the effect of particulate matter（PM）on stroke.Secondly,the estimates of air pollution exposure were limited to population levels,not to individual levels.Finally,the impacts of lifestyles,such as body mass index（BMI）,smoking,drinking,diets and sedentary,on the association between air pollution and stroke have not been fully studied.Herein,we performed a series of studies to provide robust estimates of the adverse effects of both short-term and long-term exposure to air pollution including sulfur dioxide（SO₂）,Nitrogen dioxide（NO₂）,carbon monoxide（CO）,ozone（O₃）,particulate matter less than 2.5μm(PM_2.5)and particulate matter less than 10μm(PM₁₀)on stroke in Yinzhou,China,and to provide more real-world evidence on the heterogeneity of the effects of air pollution among different subgroups.Materials and methodsOur study was divided into three parts,namely time-series study,time-stratified case-crossover study and prospective cohort study,to explore the association between both short-term and long-term exposure to air pollution and stroke.In the time-series study,we conducted an ecological study to examine the association between short-term exposure to air pollution and daily hospital visits for stroke in Yinzhou district,Ningbo,China during 2013-2019.Daily hospital visits for stroke were obtained from the Yinzhou Health Information System（YHIS）,a high-efficiency health information system originated from all health service institutions in Yinzhou.And air pollution and meteorological data including temperature（℃）and relative humidity（%）was obtained from the fixed-site air quality monitoring stations in Ningbo.We used the distributed lag nonlinear models（DLNMs）to explore the nonlinear exposure-response association between air pollution and daily hospital visits for stroke.Since hospital visits for stroke were commonly considered as rare events,we constructed generalized additive models（GAMs）extended quasi-Poisson regression to estimate the effects of air pollution.Then we conducted a time-stratified case-crossover study to explore the acute adverse health effect of short-term exposure to air pollution on stroke onset in Yinzhou.In this time-stratified case-crossover study,stroke onset cases were selected from our study cohort and air pollution data was obtained from the fixed-site air quality monitoring stations in Zhejiang Province.We used an inverse distance weighted（IDW）method to calculate individual levels of short-term exposure to air pollution for all the cases according to their residential addresses and the distances to the fixed-site air quality monitoring stations.The time-stratified case-crossover desigh was used to control the confounding effects and conditional logistic regression models were used to estimate the relationship between short-term exposure to air pollution and risk of stroke onset.Finally,we performed a prospective cohort study to explore long-term effects of exposure to air pollution and risk of stroke incidence.Subjects with a history of stroke were excluded in this study.We also used the IDW method to calculate individual levels of long-term exposure to air pollution for all subjects in our cohort and used the Cox regression models to estimate the association between air pollution and risk of stroke incidence.The impact of lifestyle factors including BMI,smoking,drinking and physical activityon such association was further explored in subgroup analyses.ResultsA total of 341,059 hospital visits admitted for stroke from YHIS during the 7-year study period were finally included in the analyses after excluding repeated visits from January,2013 to December,2019.We found that short-term exposure to O₃ and PM₁₀was significantly associated with increased cumulative risk of hospital visits for stroke,and the maximum corresponding cumulative risk ratios（CRRs）were 1.15（95%CI:1.06-1.26）and 1.44（95%CI:1.01-2.04）,respectively.The results also suggested that SO₂,NO₂,CO,O₃ and PM₁₀had positive exposure-lag-response effects on hospital visits for stroke on different lag days.The adverse effects of O₃ and PM₁₀were robust in multi-pollutant models and short-term exposure to PM_2.5was also significantly associated with increased hospital visits for stroke in multi-pollutant models.In subgroup analyses,significant associations between O₃ and hospital visits for stroke were observed both for the young and the elderly,and no difference was observed among different age groups.Significant association was observed for PM₁₀among the young.Short-term exposure to air pollution had a stronger impact on hospital visits for stroke among women,and PM_2.5 was also significantly associated with stroke among women.Stronger cumulative risks of air pollution were observed for NO₂,PM_2.5and PM₁₀ and hospital visits for stroke in spring.We also observed significant associations for NO₂ and in auntunm and for CO in winter.However,no significant association was observed in summer.In the time-stratified case-crossover study,a total of 3,791 subjects diagnosed with stroke onset were included in the final analyses with an average age of 67.8 years.In this study,we found that short-term exposure to NO₂ was significantly associated with an increased risk of stroke onset.Significant associations were observed between NO₂ and risk of stroke onset from lag1-lag4 with the corresponding odds ratios（ORs）were 1.10 per Interquartile range（IQR）increase（all P-values<0.05）.And the strongest associations were observed between the 5-day and 7-day moving average concentrations of NO₂ and risk of stroke onset（ORs:1.27,95%CI:1.12-1.45and 1.10-1.47,respectively,per IQR increase）.However,exposure to O₃ seemed to have a protective effect on risk of stroke onset,the ORs were 0.91（95%CI:0.83-0.99）at lag04 and 0.90（95%CI:0.82-0.99）at lag06,respectively.In subgroup analyses,we found that there were no significant differences among different age and sex groups.Short-term exposure to NO₂ had an adverse effect on storke onset in spring and the effect peaked in autumn.Short-term exposure to CO also had an adverse effect on storke onset in autumn while O₃ seemed to have a protective effect on storke onset at the same time.Notably,we found that subjects who were underweight,ever smokers and ever alcohol drinkers suffered a higher risk of stroke onset when short-term exposure to air pollution.And for physical activity,significant association was observed for NO₂and risk of stroke onset among subjects who hardly exercise per week.In the prospective cohort study,a total of 32,585 residents（including 13,398 men and 19,187 women）aged over 18 years were finally included in final analyses based on the YHIS.During 114,217.9 person-years of follow-up,we finally identified 3,655new cases for stroke,including 279 for ischemic stroke,25 for hemorrhagic stroke and3,351 for unspecified stroke.We found that long-term exposure to NO₂,CO,PM_2.5 and PM₁₀was significantly associated with risk of stroke incidence after adjustment for sex,age,marital status,education,annual household income,history of chronic disease（including hypertension and diabetes）and lifestyle factors（including BMI,smoking,drinking and physical activity）,the highest HRs were 1.22（95%CI:1.04-1.42）for NO₂,1.22（95%CI:1.06-1.41）for CO,1.14（95%CI:1.01-1.28）for PM_2.5 and1.14（95%CI:1.01-1.28）for PM₁₀.However,O₃ had a protective effect on stroke,the corresponding HR was 0.87（95%CI:0.77-0.98）.Compared with ischemic stroke,the adverse effect of air pollution was stronger for unspecified stroke.The highest exposure level of PM_2.5 had a significant adverse effect on unspecified stroke,and the corresponding HR was 1.16（95%CI:1.04-1.30）.The effects of long-term exposure to air pollution on the risk of stroke were heterogeneous among different subgroups.Stronger associations were observed for long-term exposure to air pollution(SO₂,NO₂,CO,PM_2.5 and PM₁₀)and risk of stroke incidence among the elderly.However,results were inconsistent between men and women.In subgroup analyses stratified by lifestyle factors,we found that underweight subjects suffered a higher risk of stroke from long-term exposure to air pollution,while no associations were observed for normal weight or overweight/obese subjects.Notably,subjects who were nonsmokers or nondrinkers suffered a higher risk of stroke than those who were currently smoking and drinking.And for physical activity,long-term exposure to air pollution was associated with a higher risk of stroke incidence among subjects who hardly exercise per week.ConclusionsIn summary,we found positive associations of both short-term and long-term exposure to air pollution with risk of stroke.Our results suggested that the effects of air pollution on stroke observed in Yinzhou were quite different from those in other countries and districts,which may be due to the differences in overall exposure levels of air pollution,susceptibility,demographic characteristics and socioeconomic factors of subjects.Our study contributed to the limited knowledge of the effects of air pollution on stroke in China.Further prospective studies with a large sample size and appropriate design are necessary in the future.