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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, Concepción Moreno-Iribas, Margareta Norberg, Kim Overvad, Salvatore Panico, J Ramón Quirós, 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, Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis, European Heart Journal, Volume 39, Issue 5, 01 February 2018, Pages 397–406, https://doi.org/10.1093/eurheartj/ehx448
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Abstract
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.
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.
Comments
We read with interest the report by Lassale and colleagues that irrespective of metabolic health, overweight and obese people have higher coronary heart disease (CHD) risk than lean people. Recently, we happen to be preforming a meta-analysis of prospective cohort studies to evaluate whether metabolically healthy obese patients carry an elevated risk of cardiovascular disease (CVD) and all-cause mortality. We include the prospective cohort studies with six mutually exclusive groups including: 1) metabolically healthy and normal weight (MHN), 2) metabolically healthy and overweight (MH-OW), 3) metabolically healthy obese (MHO), 4) metabolically unhealthy normal weight (MU-NW), 5) metabolically unhealthy overweight (MU-OW), and 6) metabolically unhealthy obese (MUO).
Nine studies are included in the meta-analysis. In agreement with the results of the Lassale et al, the results of meta-analysis based on nine studies find that both overweight and obese people with metabolic health confer a significant increased risk of CVD [MHN: Referent; MH-OW: HR = 1.19, 95% CI: 1.08, 1.29; MHO: HR = 1.27, 95% CI: 1.06, 1.47; MU-NW: HR = 1.73, 95% CI: 1.50, 1.97; MU-OW: HR = 1.72, 95% CI: 1.41, 2.03; MUO: HR = 2.07, 95% CI: 1.66, 2.49]. Absolutely, MH-OW and MHO phenotypes are associated with lower risk than the metabolically unhealthy overweight and obese. However, the results of meta-analysis based on three studies find MHO phenotype did not confer a higher for all-cause mortality [MHN: Referent; MH-OW: HR = 1.36, 95% CI: 1.05, 1.66; MHO: HR = 1.05, 95% CI: 0.85, 1.24; MU-NW: HR = 1.32, 95% CI: 1.11, 1.54; MU-OW: HR = 1.52, 95% CI: 1.11, 1.93; MUO: HR = 1.94, 95% CI: 1.42, 2.46]. The three limited number of included studies may retard our exploration of the reason, and it may be necessary to evaluate the association of ‘metabolically healthy obesity’ with all-cause mortality.
Yafeng Wang, Zhaoqiang Cui
Cardiovascular Department
Fudan University Zhongshan hospital
Shanghai, China
E-mail: [email protected]