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

Camille Lassale, Ioanna Tzoulaki, K. G M Moons, Michael Sweeting, Jolanda Boer, Laura Johnson, Adam S Butterworth

Research output: Contribution to journalArticle (Academic Journal)peer-review

188 Citations (Scopus)
419 Downloads (Pure)


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 median follow-up of 12.2 years, we recorded 7,637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using BMI, and metabolic dysfunction (“unhealthy”) as ≥3 of elevated blood pressure, hypertriglyceridemia, low HDL-cholesterol, hyperglycemia, 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 to 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 to 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.
Original languageEnglish
Article numberehx448
Pages (from-to)397–406
Number of pages12
JournalEuropean Heart Journal
Issue number5
Early online date14 Aug 2017
Publication statusPublished - 1 Feb 2018

Bibliographical note

Other co-authors
José María Huerta7,8, Claudia Agnoli9, Heinz Freisling10, Elisabete Weiderpass11-14, Patrik Wennberg15, Daphne van der A5, Larraitz Arriola16, Vassiliki Benetou17,18, Heiner Boeing19, Fabrice Bonnet20,21 Sandra M. Colorado-Yohar7,22, Gunnar Engström23, Anne K Eriksen24, Pietro Ferrari10, Sara Grioni9, Matthias Johansson10, Rudolf Kaaks25, Michail Katsoulis18, Verena Katzke25, Timothy J Key26, Giuseppe Matullo27,28 Olle Melander23, Elena Molina-Portillo8,29, Concepción Moreno-Iribas30, Margareta Norberg31, Kim Overvad32,33, Salvatore Panico34, J. Ramón Quirós35, Calogero Saieva36, Guri Skeie37, Annika Steffen19, Magdalena Stepien10, Anne Tjønneland24, Antonia Trichopoulou17,18, Rosario Tumino38, Yvonne T. van der Schouw3, W.M.Monique Verschuren3,5, Claudia Langenberg39, Emanuele Di Angelantonio4, Elio Riboli2, Nicholas J Wareham39, John Danesh4


  • Coronary Heart Disease
  • Adiposity
  • Obesity
  • Metabolic syndrome
  • Epidemiology


Dive into the research topics of 'Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis'. Together they form a unique fingerprint.

Cite this