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Journal of Epidemiology & Community Health Confidential: For Review Only Determinants of social inequalities in stroke incidence across Europe: a collaborative analysis of 126 635 individuals from 48 cohort studies Journal: Journal of Epidemiology & Community Health Manuscript ID jech-2017-209728.R1 Article Type: Research report Date Submitted by the Author: n/a Complete List of Authors: Ferrario, Marco; Università degli Studi dell'Insubria, Centro Ricerche EPIMED - Epidemiologia e Prevenzione Veronesi, Giovanni; Università degli Studi dell'Insubria, Centro Ricerche EPIMED - Epidemiologia e Prevenzione Kee, Frank; Queen's University Belfast, Centre for Statistical Science and Operational Research (CenSSOR) Chambless, Lloyd; University of North Carolina at Chapel Hill, Biostatistics Kuulasmaa, Kari; National Institute for Health and Welfare, Department of Chronic Disease Prevention Jørgensen, Torben; Glostrup University Hospital, Research Centre for Prevention and Health; University of Copenhagen, Faculty of Health Sciences Amouyel, Philippe; Institut Pasteur de Lille, The Lille MONICA project; INSERM, U744 Arveiler, Dominique ; University of Strasbourg, Epidemiology and Public Health Bobak, Martin; University College London, Epidemiology and Public Health Cesana, Giancarlo; Università di Milano – Bicocca, Dipartimento di Medicina Clinica e Preventiva Drygas, Wojciech ; National Institute of Cardiology, Epidemiology, CVD Prevention and Health Promotion Ferrieres, Jean; Département d’Epidémiologie, Université Paul Sabatier, The Toulouse MONICA Project, INSERM, U558 Giampaoli, Simona; Istituto Superiore di Sanita, Cardiovascular Dysmetabolic and Ageing –Associated DiseasesCardiovascular Dysmetabolic and Ageing –Associated Diseases Iacoviello, Licia; NEUROMED, Epidemiology and Prevention Nikitin, Yuri; Institute of Internal and Preventive Medicine Pajak, Andrzej; Institute of Public Health, Department of Epidemiology and Population Sciences Peters, Annette; Helmholtz-Zentrum München, Institute of Epidemiology II Salomaa, Veikko; National Institute for Health and Welfare, Department of Chronic Disease Prevention Soderberg, Stefan; Umeå University, Public Health and Clinical Medicine, Cardiology and Heart Centre Tamosiunas, Abdonas ; Lithuanian University of Health Sciences, Institute https://mc.manuscriptcentral.com/jech Page 1 of 34 Journal of Epidemiology & Community Health 1 2 3 4 of Cardiology 5 Wilsgaard, Tom; UiT The Arctic University of Norway, Department of Community Medicine 6 Tunstall-Pedoe, Hugh; University of Dundee, Ninewells Hospital, Dundee 7 DD1 9SY, UK; , Cardiovascular Epidemiology Unit, Instit 8 Confidential: For Review Only 9 Keywords: STROKE, SOCIAL INEQUALITIES, SOCIAL EPIDEMIOLOGY, Cohort studies 10 11 12 13 14 15 16 17 18 19 20 This article has been accepted for publication in Journal of Epidemiology and Community Health 21 following peer review. The definitive copyedited, typeset version Ferrario MM, Veronesi G, Kee F on 22 behalf of the MORGAM Project, et al Determinants of social inequalities in stroke incidence across 23 Europe: a collaborative analysis of 126635 individuals from 48 cohort studies J Epidemiol Community 24 25 Health 2017;71:1210-1216. is available online at: http://jech.bmj.com/content/71/12/1210 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/jech Journal of Epidemiology & Community Health Page 2 of 34 1 2 3 4 Determinants of social inequalities in stroke incidence across Europe: a collaborative 5 analysis of 126 635 individuals from 48 cohort studies 6 7 Ferrario MM 1*, Veronesi G1*, Kee F2, Chambless LE 3, Kuulasmaa K4, Jørgensen T5,6,7 , Amouyel P8, 8 Confidential:Arveiler D9, Bobak M10 , Cesana G11 , Drygas For W12 , Ferrieres Review J13 , Giampaoli S14 , Iacoviello Only L1,15, Nikitin 9 Y16 , Pajak A17 , Peters A18 , Salomaa V4, Soderberg S19 , Tamosiunas A20 , Wilsgaard T21 , Tunstall- 10 Pedoe H22 ; on behalf of the MORGAM Project. 11 12 *: These authors contributed equally to the paper. 13 1 Centro Ricerche EPIMED – Epidemiologia e Medicina Preventiva, Università degli Studi 14 dell'Insubria, Varese, Italy 15 2 UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast, UK. 16 3 Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 17 4 THL-National Institute for Health and Welfare, Helsinki, Finland 18 5 Research Centre for Prevention and Health, Capital Region of Denmark, Denmark 19 6 Department of Public Health, Faculty of Medical Science, University of Copenhagen, Denmark 20 7 Faculty of Medicine, Aalborg University, Denmark 21 8 Department of Epidemiology & Public Health, Pasteur Institute of Lille, Lille, France 22 9 Department of Epidemiology and Public Health, EA 3430, FMTS, University of Strasbourg, 23 Strasbourg, France 24 10 Research Department of Epidemiology and Public Health, University College London, London, 25 UK 26 27 11 Centro Studi e Ricerche in Sanità Pubblica, Università degli Studi di Milano-Bicocca, Monza, Italy 28 12 Department of Epidemiology, CVD Prevention and Health Promotion, National Institute of 29 Cardiology, Warsaw, Poland 30 13 Department of Cardiology, Toulouse University School of Medicine, Toulouse, France 31 14 Department of Cardiovascular Dysmetabolic and Ageing –Associated Diseases, Istituto Superiore 32 di Sanità, Rome, Italy 33 15 Department of Epidemiology and Prevention. IRCCS Istituto Neurologico Mediterraneo 34 Neuromed, Pozzilli (IS), Italy 35 16 The Institute of Internal and Preventive Medicine, Novosibirsk, Russian Federation 36 17 Department of Epidemiology and Population Studies, Faculty of Health Sciences, Jagiellonian 37 University Medical College, Kraków, Poland 38 18 Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, 39 Germany 40 19 Department of Public Health and Clinical Medicine, Cardiology and Heart Centre, Umeå 41 University, Umeå, Sweden 42 20 Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania. 43 21 Department of Community Medicine, UiT The Arctic University of Norway, Tromsø 44 Norway 45 22 Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, 46 Dundee, UK. 47 Corresponding author: 48 Professor Marco M Ferrario 49 Centro Ricerche EPIMED – Epidemiologia e Medicina Preventiva. Università degli studi 50 51 dell'Insubria. 52 Via O. Rossi, 9 21100 Varese, Italy. Phone: +39 0332 270 696; Fax: +39 0332 270698 53 http://epimed.uninsubria.eu 54 [email protected] 55 Keywords : educational class, inequalities, stroke, incidence, Europe, social determinants 56 Word count: 3636 . Reference count: 29 57 58 59 60 https://mc.manuscriptcentral.com/jech 1 Page 3 of 34 Journal of Epidemiology & Community Health 1 2 3 4 Abstract (word count 273) 5 6 7 Background. Knowledge on the origins of the social gradient in stroke incidence in different 8 Confidential: For Review Only 9 populations is limited. This study aims to estimate the burden of educational class inequalities 10 11 in stroke incidence and to assess the contribution of risk factors in determining these 12 13 14 inequalities across Europe. 15 16 Methods. The MORGAM Study comprises 48 cohorts recruited mostly in the 1980s and 17 18 1990s in 4 European regions using standardized procedures for baseline risk factor 19 20 assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. 21 22 Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, 23 24 25 generating 3788 first stroke events during a median follow-up of 10 years, we estimated 26 27 differences in stroke rates and hazard ratios for the least vs. the most educated individuals. 28 29 Results. Compared to their most educated counterparts, the overall age-adjusted excess 30 31 hazard for stroke was 1.54 (95%CI: 1.25-1.91) and 1.41 (1.16-1.71) in least educated men 32 33 34 and women, respectively, with little heterogeneity across populations. Educational class 35 36 inequalities accounted for 86-413 and 78-156 additional stroke events per 100,000 person- 37 38 years in the least compared to most educated men and women, respectively. The additional 39 40 events were equivalent to 47%-130% and to 40%-89% of the average incidence rates. 41 42 Inequalities in risk factors accounted for 45%-70% of the social gap in incidence in the 43 44 45 Nordic Countries, the UK and Lithuania-Kaunas (men); but for no more than 17% in Central 46 47 and South Europe. The major contributors were cigarette smoking, alcohol intake and body 48 49 mass index. 50 51 Conclusions . Social inequalities in stroke incidence contribute substantially to the disease 52 53 54 rates in Europe. Healthier life-styles in the most disadvantaged individuals should have a 55 56 prominent impact in reducing both inequalities and the stroke burden. 57 58 59 60 https://mc.manuscriptcentral.com/jech 2 Journal of Epidemiology & Community Health Page 4 of 34 1 2 3 4 What is already known on this subject 5 6 7 - Two recent reviews and one meta-analysis highlighted the increased risk of stroke among 8 Confidential:lower socio-economic classes. For Review Only 9 10 - However, current knowledge on the origins of social inequalities in stroke across Europe 11 12 hinder the possibility to prioritize interventions that might help close the social gap in 13 14 different populations 15 16 What this study adds 17 18 - Our collaborative