Long-term exposure to air pollution and cerebrovascular disease: findings from Beijing Health Management Cohort study

Highlights

● This study explored the long-term association by double robust additive models.

● Individual exposure concentrations were assessed by integrating GAM, LUR and BPNN.

● PM_2.5, SO₂ and NO₂ are positively associated with cerebrovascular disease.

● CO could reduce the risk of cerebrovascular disease with the highest robustness.

● The elderly, women and people with normal BMI are at higher risk for air pollution.

Abstract

The relationship between air pollution and cerebrovascular disease has become a popular topic, yet research findings are highly heterogeneous. This study aims to investigate this association based on detailed individual health data and a precise evaluation of their exposure levels. The integrated models of generalized additive model, land use regression model and back propagation neural network were used to evaluate the exposure concentrations. And doubly robust additive model was conducted to explore the association between cerebrovascular disease and air pollution after adjusted for demographic characteristics, physical examination, disease information, geographic and socioeconomic status. A total of 25097 subjects were included in the Beijing Health Management Cohort from 2013 to 2018. With a 1 μg/m³ increase in the concentrations of PM_2.5, SO₂ and NO₂, the incidence risk of cerebrovascular disease increased by 1.02 (95% CI: 1.008–1.034), 1.06 (95% CI: 1.034–1.095) and 1.02 (95% CI: 1.010–1.029) respectively. Whereas CO exposure could decrease the risk, with an odds ratio of 0.38 (95% CI: 0.212–0.626). In the subgroup analysis, individuals under the age of 50 with normal BMI were at higher risk caused by PM_2.5, and SO₂ was considered more hazardous to women. Meanwhile, the protective effect of CO on women and those with normal BMI was stronger. Successful reduction of long-term exposure to PM_2.5, SO₂ and NO₂ would lead to substantial benefits for decrease the risk of cerebrovascular disease especially for the health of the susceptible individuals.

Graphical abstract

Keywords

Air pollution / Cerebrovascular disease / Incidence / Long-term exposure / Doubly robust additive model

References

[1] Alimohammadi H , Fakhri S , Derakhshanfar H , Hosseini-Zijoud S M , Safari S , Hatamabadi H R . (2016). The effects of air pollution on ischemic stroke admission rate. Chonnam Medical Journal, 52(1): 53–58

[2] Amini H , Dehlendorff C , Lim Y H , Mehta A , Jørgensen J T , Mortensen L H , Westendorp R , Hoffmann B , Loft S , Cole-Hunter T . . (2020). Long-term exposure to air pollution and stroke incidence: a Danish Nurse Cohort study. Environment International, 142: 105891

[3] Atkinson R W , Carey I M , Kent A J , van Staa T P , Anderson H R , Cook D G . (2013). Long-term exposure to outdoor air pollution and incidence of cardiovascular diseases. Epidemiology (Cambridge, Mass.), 24(1): 44–53

[4] Beelen R , Stafoggia M , Raaschou-Nielsen O , Andersen Z J , Xun W W , Katsouyanni K , Dimakopoulou K , Brunekreef B , Weinmayr G , Hoffmann B . . (2014). Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts. Epidemiology (Cambridge, Mass.), 25(3): 368–378

[5] Beristain-Montiel E , Villalobos-Pietrini R , Arias-Loaiza G E , Gómez-Arroyo S L , Amador-Muñoz O . (2016). An innovative ultrasound assisted extraction micro-scale cell combined with gas chromatography/mass spectrometry in negative chemical ionization to determine persistent organic pollutants in air particulate matter. Journal of Chromatography A, 1477: 100–107

[6] Brüne B , Ullrich V . (1987). Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Molecular Pharmacology, 32: 497–504

[7] Brzecka A , Ejma M . (2015). Obesity paradox in the course of cerebrovascular diseases. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, 24: 379–383

[8] Cohen A J , Brauer M , Burnett R , Anderson H R , Frostad J , Estep K , Balakrishnan K , Brunekreef B , Dandona L , Dandona R . . (2017). Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet, 389(10082): 1907–1918

[9] Danesh Yazdi M , Wang Y , Di Q , Wei Y , Requia W J , Shi L , Sabath M B , Dominici F , Coull B A , Evans J S . . (2021). Long-term association of air pollution and hospital admissions among medicare participants using a doubly robust additive model. Circulation, 143(16): 1584–1596

[10] Di Q , Amini H , Shi L , Kloog I , Silvern R , Kelly J , Sabath M B , Choirat C , Koutrakis P , Lyapustin A . . (2019). An ensemble-based model of PM_2.5 concentrations across the contiguous United States with high spatiotemporal resolution. Environment International, 130: 104909

[11] Di Q , Amini H , Shi L , Kloog I , Silvern R , Kelly J , Sabath M B , Choirat C , Koutrakis P , Lyapustin A . . (2020). Assessing NO₂ concentrations and model uncertainty with high spatiotemporal resolution across the contiguous United States using ensemble model averaging. Environmental Science & Technology, 54(3): 1372–1384

[12] Dirnagl U , Simon R P , Hallenbeck J M . (2003). Ischemic tolerance and endogenous neuroprotection. Trends in Neurosciences, 26(5): 248–254

[13] Donaldson K , Duffin R , Langrish J P , Miller M R , Mills N L , Poland C A , Raftis J , Shah A , Shaw C A , Newby D E . (2013). Nanoparticles and the cardiovascular system: a critical review. Nanomedicine (London), 8(3): 403–423

[14] Dong H , Yu Y , Yao S , Lu Y , Chen Z , Li G , Yao Y , Yao X , Wang S L , Zhang Z . (2018). Acute effects of air pollution on ischaemic stroke onset and deaths: a time-series study in Changzhou, China. BMJ Open, 8(7): e20425

[15] Funk M J , Westreich D , Wiesen C , Stürmer T , Brookhart M A , Davidian M . (2011). Doubly robust estimation of causal effects. American Journal of Epidemiology, 173(7): 761–767

[16] Garcia J M , Teodoro F , Cerdeira R , Coelho L M , Kumar P , Carvalho M G . (2016). Developing a methodology to predict PM₁₀ concentrations in urban areas using generalized linear models. Environmental Technology, 37(18): 2316–2325

[17] GBD 2015 DALYs , HALE Collaborators . (2016). Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet, 388(10053): 1603–1658

[18] Gu J , Shi Y , Chen N , Wang H , Chen T . (2020). Ambient fine particulate matter and hospital admissions for ischemic and hemorrhagic strokes and transient ischemic attack in 248 Chinese cities. Science of the Total Environment, 715: 136896

[19] Hanafy K A , Oh J , Otterbein L E . (2013). Carbon Monoxide and the brain: time to rethink the dogma. Current Pharmaceutical Design, 19(15): 2771–2775

[20] Hayes R B , Lim C , Zhang Y , Cromar K , Shao Y , Reynolds H R , Silverman D T , Jones R R , Park Y , Jerrett M , Ahn J , Thurston G D . (2020). PM_2.5 air pollution and cause-specific cardiovascular disease mortality. International Journal of Epidemiology, 49(1): 25–35

[21] Hong N S , Kim K S , Lee I K , Lind P M , Lind L , Jacobs D R , Lee D H . (2012). The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox. International Journal of Obesity, 36(9): 1170–1175

[22] Huang K , Liang F , Yang X , Liu F , Li J , Xiao Q , Chen J , Liu X , Cao J , Shen C . . (2019). Long term exposure to ambient fine particulate matter and incidence of stroke: Prospective cohort study from the China-PAR project. BMJ (Clinical Research Ed.), 367: l6720

[23] Johnson M , Brook J R , Brook R D , Oiamo T H , Luginaah I , Peters P A , Spence J D . (2020). Traffic-related air pollution and carotid plaque burden in a Canadian city with low-level ambient pollution. Journal of the American Heart Association, 9(7): e013400

[24] Kim H , Kim J , Kim S , Kang S H , Kim H J , Kim H , Heo J , Yi S M , Kim K , Youn T J . . (2017). Cardiovascular effects of long-term exposure to air pollution: a population-based study with 900845 person-years of follow up. Journal of the American Heart Association, 6(11): e007170

[25] Lavie C J , Osman A F , Milani R V , Mehra M R . (2003). Body composition and prognosis in chronic systolic heart failure: the obesity paradox. American Journal of Cardiology, 91(7): 891–894

[26] Le Y , Hu X , Zhu J , Wang C , Yang Z , Lu D . (2019). Ambient fine particulate matter induces inflammatory responses of vascular endothelial cells through activating TLR-mediated pathway. Toxicology and Industrial Health, 35(10): 670–678

[27] Liang F , Liu F , Huang K , Yang X , Li J , Xiao Q , Chen J , Liu X , Cao J , Shen C . . (2020). Long-term exposure to fine particulate matter and cardiovascular disease in China. Journal of the American College of Cardiology, 75(7): 707–717

[28] Liu B , Guo X , Lai M , Wang Q . (2020a). Air pollutant concentrations forecasting using long short-term memory based on wavelet transform and information gain: a case study of Beijing. Computational Intelligence and Neuroscience, 2020: 8834699

[29] Liu C , Yin P , Chen R , Meng X , Wang L , Niu Y , Lin Z , Liu Y , Liu J , Qi J . . (2018). Ambient carbon monoxide and cardiovascular mortality: a nationwide time-series analysis in 272 cities in China. Lancet. Planetary Health, 2(1): e12–e18

[30] Liu G , Sun B , Yu L , Chen J , Han B , Li Y , Chen J . (2020b). The gender-based differences in vulnerability to ambient air pollution and cerebrovascular disease mortality: Evidences based on 26781 deaths. Global Heart, 15(1): 46

[31] Maheswaran R , Pearson T , Smeeton N C , Beevers S D , Campbell M J , Wolfe C D . (2010). Impact of outdoor air pollution on survival after stroke. Stroke, 41(5): 869–877

[32] Miller K A , Siscovick D S , Sheppard L , Shepherd K , Sullivan J H , Anderson G L , Kaufman J D . (2007). Long-term exposure to air pollution and incidence of cardiovascular events in women. New England Journal of Medicine, 356(5): 447–458

[33] Montresor-López J A , Yanosky J D , Mittleman M A , Sapkota A , He X , Hibbert J D , Wirth M D , Puett R C . (2016). Short-term exposure to ambient ozone and stroke hospital admission: a case-crossover analysis. Journal of Exposure Science & Environmental Epidemiology, 26(2): 162–166

[34] National Bureau of Statistics of China (2021). China Statistical Yearbook 2021. Beijing, China: China Statistics Press (in Chinese)

[35] O'Donnell M J , Fang J , Mittleman M A , Kapral M K , Wellenius G A , the Investigators of the Registry of Canadian Stroke Network . (2011). Fine particulate air pollution (PM_2.5) and the risk of acute ischemic stroke. Epidemiology (Cambridge, Mass.), 22(3): 422–431

[36] Oudin A , Strömberg U , Jakobsson K , Stroh E , Björk J . (2010). Estimation of short-term effects of air pollution on stroke hospital admissions in southern Sweden. Neuroepidemiology, 34(3): 131–142

[37] Power M C , Lamichhane A P , Liao D , Xu X , Jack C R , Gottesman R F , Mosley T , Stewart J D , Yanosky J D , Whitsel E A . (2018). The association of long-term Exposure to particulate matter air pollution with brain MRI findings: the ARIC Study. Environmental Health Perspectives, 126(2): 027009

[38] Qin X D , Qian Z , Vaughn M G , Trevathan E , Emo B , Paul G , Ren W H , Hao Y T , Dong G H . (2015). Gender-specific differences of interaction between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study. Science of the Total Environment, 529: 243–248

[39] Qiu H , Sun S , Tsang H , Wong C M , Lee R S , Schooling C M , Tian L . (2017). Fine particulate matter exposure and incidence of stroke. Neurology, 88(18): 1709–1717

[40] Raub J A , Benignus V A . (2002). Carbon monoxide and the nervous system. Neuroscience and Biobehavioral Reviews, 26(8): 925–940

[41] Requia W J , Di Q , Silvern R , Kelly J T , Koutrakis P , Mickley L J , Sulprizio M P , Amini H , Shi L , Schwartz J . (2020). An ensemble learning approach for estimating high spatiotemporal resolution of Ground-Level ozone in the contiguous United States. Environmental Science & Technology, 54(18): 11037–11047

[42] Rodins V , Lucht S , Ohlwein S , Hennig F , Soppa V , Erbel R , Jöckel K H , Weimar C , Hermann D M , Schramm S . . (2020). Long-term exposure to ambient source-specific particulate matter and its components and incidence of cardiovascular events: the Heinz Nixdorf Recall study. Environment International, 142: 105854

[43] Samoli E , Stafoggia M , Rodopoulou S , Ostro B , Declercq C , Alessandrini E , Díaz J , Karanasiou A , Kelessis A G , Le Tertre A , . MED-PARTICLES Study Group . . (2013). Associations between fine and coarse particles and mortality in Mediterranean cities: Results from the MED-PARTICLES project. Environmental Health Perspectives, 121(8): 932–938

[44] Sang N , Yun Y , Li H , Hou L , Han M , Li G . (2010). SO₂ inhalation contributes to the development and progression of ischemic stroke in the brain. Toxicological Sciences, 114(2): 226–236

[45] Shin J , Choi J , Kim K J . (2019). Association between long-term exposure of ambient air pollutants and cardiometabolic diseases: a 2012 Korean community health survey. Nutrition, Metabolism, and Cardiovascular Diseases, 29(2): 144–151

[46] Stafoggia M , Cesaroni G , Peters A , Andersen Z J , Badaloni C , Beelen R , Caracciolo B , Cyrys J , De Faire U , De Hoogh K . . (2014). Long-term exposure to ambient air pollution and incidence of cerebrovascular events: Results from 11 European cohorts within the ESCAPE project. Environmental Health Perspectives, 122(9): 919–925

[47] Tian L , Qiu H , Pun V C , Ho K F , Chan C S , Yu I T . (2015). Carbon monoxide and stroke: A time series study of ambient air pollution and emergency hospitalizations. International Journal of Cardiology, 201: 4–9

[48] Tian Y , Liu H , Zhao Z , Xiang X , Li M , Juan J , Song J , Cao Y , Wang X , Chen L . . (2018). Association between ambient air pollution and daily hospital admissions for ischemic stroke: a nationwide time-series analysis. PLoS Medicine, 15(10): e1002668

[49] United States Environmental Protection Agency (2010). Integrated science assessment for carbon monoxide (Full report). Washington DC: USEPA

[50] VanderWeele T J , Ding P . (2017). Sensitivity analysis in observational research: introducing the E-value. Annals of Internal Medicine, 167(4): 268–274

[51] Wagner C T , Durante W , Christodoulides N , Hellums J D , Schafer A I . (1997). Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. Journal of Clinical Investigation, 100(3): 589–596

[52] Wang L , Liu C , Meng X , Niu Y , Lin Z , Liu Y , Liu J , Qi J , You J , Tse L A . . (2018). Associations between short-term exposure to ambient sulfur dioxide and increased cause-specific mortality in 272 Chinese cities. Environment International, 117: 33–39

[53] Wolf K , Hoffmann B , Andersen Z J , Atkinson R W , Bauwelinck M , Bellander T , Brandt J , Brunekreef B , Cesaroni G , Chen J . . (2021). Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project. Lancet. Planetary Health, 5(9): e620–e632

[54] Xiao F , Yang M , Fan H , Fan G , Al-Qaness M A A . (2020). An improved deep learning model for predicting daily PM_2.5 concentrations. Scientific Reports, 10(1): 20988

[55] Yitshak Sade M , Novack V , Ifergane G , Horev A , Kloog I . (2015). Air pollution and ischemic stroke among young adults. Stroke, 46(12): 3348–3353

[56] Yu Y , Dong H , Yao S , Ji M , Yao X , Zhang Z . (2017). Protective effects of ambient ozone on incidence and outcomes of ischemic stroke in Changzhou, China: a time-series study. International Journal of Environmental Research and Public Health, 14(12): 1610

[57] Yuan K , Chen J , Xu P , Zhang X , Gong X , Wu M , Xie Y , Wang H , Xu G , Liu X . (2020). A nomogram for predicting stroke recurrence among young adults. Stroke, 51(6): 1865–1867

[58] Zhang L , An J , Liu M , Li Z , Liu Y , Tao L , Liu X , Zhang F , Zheng D , Gao Q . . (2020). Spatiotemporal variations and influencing factors of PM_2.5 concentrations in Beijing, China. Environmental Pollution (Barking, Essex: 1987), 262: 114276

[59] Zhang P , Dong G , Sun B , Zhang L , Chen X , Ma N , Yu F , Guo H , Huang H , Lee Y L . . (2011). Long-term exposure to ambient air pollution and mortality due to cardiovascular disease and cerebrovascular disease in Shenyang, China. PLoS One, 6(6): e20827

[60] Zhang Z , Wang J , Chen L , Chen X , Sun G , Zhong N , Kan H , Lu W . (2014). Impact of haze and air pollution-related hazards on hospital admissions in Guangzhou, China. Environmental Science and Pollution Research International, 21(6): 4236–4244

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81773512). The funding source had no role in the design of the study; in the collection, analysis, and interpretation of data; or in the writing of the manuscript.

Declaration of Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11783-023-1684-2 and is accessible for authorized users.

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