Kathrin Wolf1, Barbara Hoffmann2, Zorana J Andersen3, Richard W Atkinson4, Mariska Bauwelinck5, Tom Bellander6, Jørgen Brandt7, Bert Brunekreef8, Giulia Cesaroni9, Jie Chen8, Ulf de Faire10, Kees de Hoogh11, Daniela Fecht12, Francesco Forastiere13, John Gulliver14, Ole Hertel15, Ulla Arthur Hvidtfeldt16, Nicole A H Janssen17, Jeanette T Jørgensen3, Klea Katsouyanni18, Matthias Ketzel19, Jochem O Klompmaker20, Anton Lager21, Shuo Liu3, Conor J MacDonald22, Patrik K E Magnusson23, Amar J Mehta24, Gabriele Nagel25, Bente Oftedal26, Nancy L Pedersen23, Göran Pershagen6, Ole Raaschou-Nielsen27, Matteo Renzi9, Debora Rizzuto28, Sophia Rodopoulou29, Evangelia Samoli29, Yvonne T van der Schouw30, Sara Schramm31, Per Schwarze32, Torben Sigsgaard33, Mette Sørensen34, Massimo Stafoggia35, Maciek Strak36, Anne Tjønneland16, W M Monique Verschuren37, Danielle Vienneau11, Gudrun Weinmayr25, Gerard Hoek8, Annette Peters38, Petter L S Ljungman39. 1. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany. Electronic address: kathrin.wolf@helmholtz-muenchen.de. 2. Institute for Occupational, Social and Environmental Medicine, Centre for Health and Society, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 3. Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 4. Population Health Research Institute, St George's, University of London, London, UK. 5. Interface Demography, Department of Sociology, Vrije Universiteit Brussel, Brussels, Belgium. 6. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden. 7. Department of Environmental Science, Aarhus University, Roskilde, Denmark; iClimate, Interdisciplinary Centre for Climate Change, Aarhus University, Denmark. 8. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands. 9. Department of Epidemiology-Lazio Regional Health Service, ASL Roma 1, Rome, Italy. 10. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 11. Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. 12. School of Public Health, Faculty of Medicine, Imperial College London, London, UK. 13. Department of Epidemiology-Lazio Regional Health Service, ASL Roma 1, Rome, Italy; School of Public Health, Faculty of Medicine, Imperial College London, London, UK. 14. School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Centre for Environmental Health and Sustainability, University of Leicester, Leicester, UK; School of Geography, Geology and the Environment, University of Leicester, Leicester, UK. 15. Department of Bioscience, Aarhus University, Roskilde, Denmark. 16. Danish Cancer Society Research Center, Copenhagen, Denmark. 17. National Institute for Public Health and the Environment, Bilthoven, Netherlands. 18. School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 19. Department of Environmental Science, Aarhus University, Roskilde, Denmark; Global Centre for Clean Air Research, University of Surrey, Surrey, UK. 20. National Institute for Public Health and the Environment, Bilthoven, Netherlands; Harvard T H Chan School of Public Health, Boston, MA, USA. 21. Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden. 22. INSERM U1018, CESP, Institut Gustave Roussy, Université Paris-Saclay, Université Paris-Sud, Villejuif, France. 23. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 24. Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 25. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. 26. Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. 27. Department of Environmental Science, Aarhus University, Roskilde, Denmark; Danish Cancer Society Research Center, Copenhagen, Denmark. 28. Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden. 29. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 30. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. 31. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 32. Global Health Cluster, Norwegian Institute of Public Health, Oslo, Norway. 33. Department of Public Health, Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark. 34. Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Natural Science and Environment, Roskilde University, Roskilde, Denmark. 35. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology-Lazio Regional Health Service, ASL Roma 1, Rome, Italy. 36. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands; National Institute for Public Health and the Environment, Bilthoven, Netherlands. 37. National Institute for Public Health and the Environment, Bilthoven, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. 38. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany; Ludwig Maximilians Universität München, Munich, Germany. 39. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 μg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 μg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 μg/m3 for PM2·5 and 40 μg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.
BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 μg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 μg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 μg/m3 for PM2·5 and 40 μg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.
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