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Olle Melander

Principal investigator

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


  • Camille Lassale
  • Ioanna Tzoulaki
  • Karel G.M. Moons
  • Michael Sweeting
  • Jolanda Boer
  • Laura Johnson
  • José María Huerta
  • Claudia Agnoli
  • Heinz Freisling
  • Elisabete Weiderpass
  • Patrik Wennberg
  • Daphne L. Van Der A
  • Larraitz Arriola
  • Vassiliki Benetou
  • Heiner Boeing
  • Fabrice Bonnet
  • Sandra M. Colorado-Yohar
  • Gunnar Engström
  • Anne K. Eriksen
  • Pietro Ferrari
  • Sara Grioni
  • Matthias Johansson
  • Rudolf Kaaks
  • Michail Katsoulis
  • Verena Katzke
  • Timothy J. Key
  • Giuseppe Matullo
  • Olle Melander
  • Elena Molina-Portillo
  • Concepcion Moreno-Iribas
  • Margareta Norberg
  • Kim Overvad
  • Salvatore Panico
  • J. Ramón Quiros
  • Calogero Saieva
  • Guri Skeie
  • Annika Steffen
  • Magdalena Stepien
  • Anne Tjønneland
  • Antonia Trichopoulou
  • Rosario Tumino
  • Yvonne T. Van Der Schouw
  • W. M.Monique Verschuren
  • Claudia Langenberg
  • Emanuele Di Angelantonio
  • Elio Riboli
  • Nicholas J. Wareham
  • John Danesh
  • Adam S. Butterworth

Summary, in English

Aims: 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. Conclusion: 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.


  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







European Heart Journal





Document type

Journal article


Oxford University Press


  • Cardiac and Cardiovascular Systems


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



Research group

  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension


  • ISSN: 0195-668X