Air Pollution and Surrounding Greenness in Relation to Ischemic Stroke: A Population-Based Cohort Study

Background: Evidence for the association between environmental exposures and ischemic stroke (IS) is limited and inconsistent. We aimed to assess the relationship between long-term exposure to air pollutants, residential surrounding greenness, and incident IS, and to identify population subgroups particularly vulnerable to these exposures. Methods: We used data from administrative health registries of the public healthcare system in Catalonia, Spain to construct a cohort of individuals aged 18 years and older without a previous stroke diagnosis at 1 st January, 2016 (n=3 521 274). We collected data on sociodemographic characteristics and cerebrovascular risk factors, and derived exposure at the participant’s residence to ambient levels of fine particulate matter (PM 2.5 ), black carbon (BC), nitrogen dioxide (NO 2 ), and Normalized Difference Vegetation Index (NDVI) in 300m buffer as an indicator of greenness. The primary outcome was IS diagnosis at any point during the follow-up. We used Cox proportional hazards models to estimate associations between environmental exposures and incident IS and stratified analyses to investigate effect modification. Findings: Between 1 st January, 2016 and 31st December, 2017, 10 865 individuals were admitted to public hospitals with an IS diagnosis. Individuals with a high residential exposure to air pollution were at greater risk of IS: HR 1·04 (95% CI:0·99-1·10) per 5µg/m 3 of PM 2.5 ; HR 1·05 (95% CI:1·00-1·10) per 1µg/m 3 of BC; HR 1·04 (95% CI:1·03-1·06) per 10µg/m 3 of NO 2 . Conversely, those individuals with higher residential surrounding green space (NDVI), had lower risk of IS (HR 0·84; CI 95%:0·7-1·0). There was no evidence of effect modification by individual characteristics. Interpretation: Higher incidence of IS was observed in relation to long-term exposures to PM 2.5 , BC and NO 2 in a region that meets European health-based air quality standards. Residential surrounding greenness was associated with lower incidence of IS.Funding: Spanish Ministries of Health, Science and Innovation and Economy and Competitiveness. Funding: The study was funded by the Spanish Ministry of Economy through the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF, PI18/00056). This project was also funded in part by the following sources: INVICTUS PLUS. FEDER, RD16/0019/0002 and the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018- 000806-S). Carla Avellaneda-Gomez was funded by a Rio Hortega fellowship (CM18/00040) awarded by the Spanish Ministry of Science and Innovation. Cathryn Tonne is funded by a Ramon y Cajal fellowship (RYC-2015-17402) awarded by the Spanish Ministry of Economy and Competitiveness. Declaration of Interest: None to declare. Ethical Approval: We received approval from our local ethics committee (code 2018/7917/I).