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Eur Heart J. 2018 Feb 1;39(5):397-406. doi: 10.1093/eurheartj/ehx448.

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis.

Author information

Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 7HB, UK.
Department of Hygiene and Epidemiology, University of Ioannina, 45110, Ioannina, Greece.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 Utrecht, The Netherlands.
Department of Public Health and Primary Care, MRC/BHF Cardiovascular Epidemiology Unit, University of Cambridge, 2 Worts' Causeway, Cambridge CB1 8RN, UK.
National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands.
Centre for Exercise, Nutrition and Health Sciences, School for Policy Studies, University of Bristol, Senate House, Tyndall Ave, Bristol BS8 1TH, UK.
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Ronda de Levante, 11, 30008, Murcia, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, 28029 Madrid, Spain.
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy.
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, 69008 Lyon, France.
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway.
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Ullernchausseen 64, 0379 Oslo, Norway.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solnavägen 1, 171 77 Solna Stockholm, Sweden.
Genetic Epidemiology Group, Folkhälsan Research Center, Topeliuksenkatu 20, 00250 Helsinki, Finland.
Department of Public Health and Clinical Medicine, Family medicine, Umeå University, 901 87 Umeå, Sweden.
Public Health Division of Gipuzkoa, Instituto Bio-Donostia, Basque Government, Calle Doctor Begiristain, 20014 Donostia/Gipuzkoa, Spain.
Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, School of Medicine, National and Kapodistrian University of Athens, Athens 157 72, Greece.
Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, 115 27, Athens, Greece.
Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114, 14558 Nuthetal, Germany.
Université de Rennes 1, CHU de Rennes, Hôpital Sud 16 bd Bulgarie, 35203 Rennes, France.
Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP), U1018, 16 Avenue Paul Vaillant Couturier, 94800 Villejuif, France.
National School of Public Health, Research Group on Demography and Health, University of Antioquia, Cl. 67 #53 - 108 Medellín, Colombia.
Department of Clinical Sciences Malmö, Lund University, Bergsgatan 31 B, 214 45 Malmö, Sweden.
Diet, Genes and Environment, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.
Human Genetics Foundation, Via Nizza 52 10126 Turin, Italy.
Department of Medical Sciences, University of Turin, Via Giuseppe Verdi, 8, 10124 Turin, Italy.
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Av. del Hospicio, s/n, 18010 Granada, Spain.
Public Health Institute of Navarra, IdiSNA, Calle de Irunlarrea, 3, 31008 Pamplona, Spain.
Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, 901 87 Umeå, Sweden.
Department of Public Health, Section for Epidemiology, Aarhus University, Nordre Ringgade 1, 8000 Aarhus, Denmark.
Department of Cardiology, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark.
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Corso Umberto I, 40, 80138 Naples, Italy.
Public Health Directorate, Asturias, General Elorza 32, 33001 Oviedo, Spain.
Cancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Via Cosimo Il Vecchio, 2, 50139 Florence, Italy.
Department of Community Medicine, University of Tromsø-the Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway.
Cancer Registry and Histopathology Unit, Civic-M.P. Arezzo Hospital, ASP Contrada Rito, 97100 Ragusa, Italy.
Medical Research Council Epidemiology Unit, University of Cambridge, 2 Worts' Causeway, Cambridge CB1 8RN, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Trinity Ln, Cambridge CB2 1TN, UK.
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.



The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study.

Methods and results:

We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses.


Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity.


Adiposity ; Coronary heart disease ; Epidemiology; Metabolic syndrome ; Obesity

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