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

• Published in: European heart journal Vol. 39; no. 5; pp. 397 - 406
• Main Authors: Lassale, Camille, Tzoulaki, Ioanna, Moons, Karel G M, Sweeting, Michael, Boer, Jolanda, Johnson, Laura, Huerta, José María, Agnoli, Claudia, Freisling, Heinz, Weiderpass, Elisabete, Wennberg, Patrik, van der A, Daphne L, Arriola, Larraitz, Benetou, Vassiliki, Boeing, Heiner, Bonnet, Fabrice, Colorado-Yohar, Sandra M, Engström, Gunnar, Eriksen, Anne K, Ferrari, Pietro, Grioni, Sara, Johansson, Matthias, Kaaks, Rudolf, Katsoulis, Michail, Katzke, Verena, Key, Timothy J, Matullo, Giuseppe, Melander, Olle, Molina-Portillo, Elena, Moreno-Iribas, Concepción, Norberg, Margareta, Overvad, Kim, Panico, Salvatore, Quirós, J Ramón, Saieva, Calogero, Skeie, Guri, Steffen, Annika, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, van der Schouw, Yvonne T, Verschuren, W M Monique, Langenberg, Claudia, Di Angelantonio, Emanuele, Riboli, Elio, Wareham, Nicholas J, Danesh, John, Butterworth, Adam S
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-02-2018
• Subjects: Adiposity; Body Mass Index; Cardiac and Cardiovascular Systems; Case-Control Studies; Clinical Medicine; Coronary Disease - complications; Coronary Disease - epidemiology; Coronary Disease - physiopathology; Coronary heart disease; Epidemiology; Europe - epidemiology; Female; Humans; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolic Syndrome; Middle Aged; Obesity; Obesity - complications; Obesity - epidemiology; Obesity - physiopathology; Europe; Obesity; Adiposity; Metabolic syndrome; Coronary heart disease; Epidemiology
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehx448

Abstract
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.