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Long-term Exposure to Air Pollution and Cardiovascular Mortality: An Analysis of 22 European Cohorts

Beelen, Roba; Stafoggia, Massimob; Raaschou-Nielsen, Olec; Andersen, Zorana Jovanovicc,d; Xun, Wei W.e,f; Katsouyanni, Kleag; Dimakopoulou, Konstantinag; Brunekreef, Berta,h; Weinmayr, Gudruni,j; Hoffmann, Barbaraj; Wolf, Kathrink; Samoli, Evangeliag; Houthuijs, Dannyl; Nieuwenhuijsen, Markm,n; Oudin, Annao; Forsberg, Bertilo; Olsson, Davido; Salomaa, Veikkop; Lanki, Timop; Yli-Tuomi, Tarjap; Oftedal, Benteq; Aamodt, Geirq; Nafstad, Perq,r; De Faire, Ulfs; Pedersen, Nancy L.t; Östenson, Claes-Göranu; Fratiglioni, Laurav; Penell, Johannas; Korek, Michals; Pyko, Andreis; Eriksen, Kirsten Thorupc; Tjønneland, Annec; Becker, Thomasw; Eeftens, Marloesa; Bots, Michielh; Meliefste, Keesa; Wang, Menga; Bueno-de-Mesquita, Basl; Sugiri, Dorotheaj; Krämer, Ursulaj; Heinrich, Joachimx; de Hoogh, Keese; Key, Timothyy; Peters, Annettek; Cyrys, Josefk,z; Concin, Hansaa; Nagel, Gabrielei,aa; Ineichen, Alexbb,cc; Schaffner, Emmanuelbb,cc; Probst-Hensch, Nicolebb,cc; Dratva, Juliabb,cc; Ducret-Stich, Reginabb,cc; Vilier, Alicedd,ee,ff; Clavel-Chapelon, Françoisedd,ee,ff; Stempfelet, Morganegg; Grioni, Sarahh; Krogh, Vittoriohh; Tsai, Ming-Yibb,cc,ii; Marcon, Alessandrojj; Ricceri, Fulviokk; Sacerdote, Carlottall; Galassi, Claudiall; Migliore, Enricall; Ranzi, Andreamm; Cesaroni, Giuliab; Badaloni, Chiarab; Forastiere, Francescob; Tamayo, Ibonn,nn; Amiano, Pilarn,nn; Dorronsoro, Mirenn,nn; Katsoulis, Michailoo; Trichopoulou, Antoniaoo; Vineis, Paoloe; Hoek, Gerarda

doi: 10.1097/EDE.0000000000000076
Air Pollution

Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death.

Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area–specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and 10 μm to 2.5 μm (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates.

Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87–1.69) per 5 μg/m3 and for PM10, 1.22 (0.91–1.63) per 10 μg/m3.

Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.

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From the aInstitute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; bDepartment of Epidemiology, Lazio Regional Health Service, Rome, Italy; cDanish Cancer Society Research Center, Copenhagen, Denmark; dCenter for Epidemiology and Screening, Department of Public Health, University of Copenhagen, CSS, København K, Denmark; eMRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, London, United Kingdom; fUniversity College London, CeLSIUS, London, United Kingdom; gDepartment of Hygiene, Epidemiology, and Medical Statistics, Medical School, University of Athens, Athens, Greece; hJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; iInstitute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; jIUF–Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany, and Medical Faculty, University of Düsseldorf, Düsseldorf, Germany; kInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; lNational Institute for Public Health and the Environment, Bilthoven, The Netherlands; mCentre for Research in Environmental Epidemiology (CREAL), Barcelona, and Parc de Recerca Biomèdica de Barcelona–PRBB (office 183.05) C. Doctor Aiguader, Barcelona, Spain; nConsortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Melchor Fernández Almagro 3-5, Madrid, Spain; oDivision of Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; pNational Institute for Health and Welfare, Kuopio, Finland; qNorwegian Institute of Public Health, Oslo, Norway; rInstitute of Health and Society, University of Oslo, Oslo, Norway; sInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; tDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; uDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; vAging Research Center, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; wDepartment of Environmental Science, Aarhus University, Roskilde, Denmark; xInstitute of Epidemiology I, Helmholtz Zentrum München, German Research Center of Environmental Health, Neuherberg, Germany; yCancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; zEnvironmental Science Center, University of Augsburg, Augsburg, Germany; aaAgency for Preventive and Social Medicine, Bregenz, Austria; bbSwiss Tropical and Public Health Institute, Basel, Switzerland; ccUniversity of Basel, Basel, Switzerland; ddInserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women’s Health Team, Villejuif, France; eeUniversity Paris Sud, UMRS 1018, Villejuif, France; ff IGR, Villejuif, France; ggFrench Institute for Public Health Surveillance (InVS) 12, Saint-Maurice, France; hhEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; iiDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA; jjUnit of Epidemiology and Medical Statistics, Department of Public Health and Community Medicine, University of Verona, Verona, Italy; kkHuman Genetics Foundation–HuGeF, Turin, Italy; llUnit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza—University of Turin and Center for Cancer Prevention, Turin, Italy; mmEnvironmental Health Reference Centre, Regional Agency for Environmental Prevention of Emilia-Romagna, Modena, Italy; nnPublic Health Division of Gipuzkoa, Basque Government, Gipuzkoa, Spain; and ooHellenic Health Foundation, Athens, Greece.

Supported by the European Community’s Seventh Framework Program (FP7/2007–2011 [grant agreement number: 211250]). For the Finnish part, additional funding received from the Academy of Finland (project number: 129317). For HUBRO, the data collection was conducted as part of the Oslo Health Study 2000–2001 and financed by the Norwegian Institute of Public Health, the University of Oslo, and the Municipality of Oslo. Financial support for the combined work with the Stockholm studies was received from the Swedish Environmental Protection Agency, the Swedish Heart-Lung Foundation, and the Swedish Council for Working Life and Social Research. The Swedish Ministry for Higher Education financially supports the Swedish Twin Register. SALT was supported by the Swedish Council for Working Life and Social Research and a grant from the NIH (grant number: AG-08724). TwinGene was supported by the Swedish Research Council (grant number: M-2005-1112), GenomEUtwin (grant numbers: EU/QLRT-2001-01254, QLG2-CT-2002-01254, NIH DK U01-066134). The Swedish Foundation for Strategic Research (SSF), and the Heart and Lung Foundation (grant number: 20070481). The EPIC-MORGEN and EPIC-PROSPECT cohorts were supported by the Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), and Statistics Netherlands. The baseline study and the mortality follow-up of SALIA were funded by the Ministry of the Environment of North-Rhine-Westfalia (Germany). The KORA research platform and the MONICA Augsburg studies were initiated and financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The VHM&PP is supported by the State of Vorarlberg, Austria. SAPALDIA received funds from the The Swiss National Science Foundation (grants numbers: 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247–065896, 3100–059302, 3200–052720, 3200–042532, 4026–028099), the Federal Office for Forest, Environment, and Landscape and several Federal and Cantonal authorities. SAPALDIA received support in mortality record linkage from the Swiss National Cohort Study (grant numbers: 108806 and 134273).

The authors report no conflicts of interest.

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Correspondence: Rob Beelen, Institute for Risk Assessment Sciences, Utrecht University PO Box 80178, 3508 TD Utrecht, The Netherlands. E-mail:

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