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 Kirstine 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

doi:10.1093/eurheartj/ehx448

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 Kirstine Eriksen, Pietro FerrariSara 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

^*Corresponding author af dette arbejde

117 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	European Heart Journal
Vol/bind	39
Udgave nummer	5
Sider (fra-til)	397-406
Antal sider	10
ISSN	0195-668X
DOI	https://doi.org/10.1093/eurheartj/ehx448
Status	Udgivet - 1 feb. 2018
Udgivet eksternt	Ja

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10.1093/eurheartj/ehx448

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Lassale, C., Tzoulaki, I., Moons, K. G. M., Sweeting, M., Boer, J., Johnson, L., Huerta, J. M., Agnoli, C., Freisling, H., Weiderpass, E., Wennberg, P., Van Der A, D. L., Arriola, L., Benetou, V., Boeing, H., Bonnet, F., Colorado-Yohar, S. M., Engström, G., Eriksen, A. K., ... Butterworth, A. S. (2018). Separate and combined associations of obesity and metabolic health with coronary heart disease: A pan-European case-cohort analysis. European Heart Journal, 39(5), 397-406. https://doi.org/10.1093/eurheartj/ehx448

Lassale, C, Tzoulaki, I, Moons, KGM, Sweeting, M, Boer, J, Johnson, L, Huerta, JM, Agnoli, C, Freisling, H, Weiderpass, E, Wennberg, P, Van Der A, DL, Arriola, L, Benetou, V, Boeing, H, Bonnet, F, Colorado-Yohar, SM, Engström, G, Eriksen, AK, Ferrari, P, Grioni, S, Johansson, M, Kaaks, R, Katsoulis, M, Katzke, V, Key, TJ, Matullo, G, Melander, O, Molina-Portillo, E, Moreno-Iribas, C, Norberg, M, Overvad, K, Panico, S, Quiros, JR, Saieva, C, Skeie, G, Steffen, A, Stepien, M, Tjønneland, A, Trichopoulou, A, Tumino, R, Van Der Schouw, YT, Verschuren, WMM, Langenberg, C, Di Angelantonio, E, Riboli, E, Wareham, NJ, Danesh, J & Butterworth, AS 2018, 'Separate and combined associations of obesity and metabolic health with coronary heart disease: A pan-European case-cohort analysis', European Heart Journal, bind 39, nr. 5, s. 397-406. https://doi.org/10.1093/eurheartj/ehx448

@article{5e0fa42ffb5847f6bee61728a1804665,

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

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.",

keywords = "Adiposity, Coronary heart disease, Epidemiology, Metabolic syndrome, Obesity",

author = "Camille Lassale and Ioanna Tzoulaki and Moons, {Karel G.M.} and Michael Sweeting and Jolanda Boer and Laura Johnson and Huerta, {Jos{\'e} Mar{\'i}a} and Claudia Agnoli and Heinz Freisling and Elisabete Weiderpass and Patrik Wennberg and {Van Der A}, {Daphne L.} and Larraitz Arriola and Vassiliki Benetou and Heiner Boeing and Fabrice Bonnet and Colorado-Yohar, {Sandra M.} and Gunnar Engstr{\"o}m and Eriksen, {Anne Kirstine} and Pietro Ferrari and Sara Grioni and Matthias Johansson and Rudolf Kaaks and Michail Katsoulis and Verena Katzke and Key, {Timothy J.} and Giuseppe Matullo and Olle Melander and Elena Molina-Portillo and Concepcion Moreno-Iribas and Margareta Norberg and Kim Overvad and Salvatore Panico and Quiros, {J. Ram{\'o}n} and Calogero Saieva and Guri Skeie and Annika Steffen and Magdalena Stepien and Anne Tj{\o}nneland and Antonia Trichopoulou and Rosario Tumino and {Van Der Schouw}, {Yvonne T.} and Verschuren, {W. M.Monique} and Claudia Langenberg and {Di Angelantonio}, Emanuele and Elio Riboli and Wareham, {Nicholas J.} and John Danesh and Butterworth, {Adam S.}",

year = "2018",

month = feb,

day = "1",

doi = "10.1093/eurheartj/ehx448",

language = "English",

volume = "39",

pages = "397--406",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Separate and combined associations of obesity and metabolic health with coronary heart disease

T2 - A pan-European case-cohort analysis

AU - Lassale, Camille

AU - Tzoulaki, Ioanna

AU - Moons, Karel G.M.

AU - Sweeting, Michael

AU - Boer, Jolanda

AU - Johnson, Laura

AU - Huerta, José María

AU - Agnoli, Claudia

AU - Freisling, Heinz

AU - Weiderpass, Elisabete

AU - Wennberg, Patrik

AU - Van Der A, Daphne L.

AU - Arriola, Larraitz

AU - Benetou, Vassiliki

AU - Boeing, Heiner

AU - Bonnet, Fabrice

AU - Colorado-Yohar, Sandra M.

AU - Engström, Gunnar

AU - Eriksen, Anne Kirstine

AU - Ferrari, Pietro

AU - Grioni, Sara

AU - Johansson, Matthias

AU - Kaaks, Rudolf

AU - Katsoulis, Michail

AU - Katzke, Verena

AU - Key, Timothy J.

AU - Matullo, Giuseppe

AU - Melander, Olle

AU - Molina-Portillo, Elena

AU - Moreno-Iribas, Concepcion

AU - Norberg, Margareta

AU - Overvad, Kim

AU - Panico, Salvatore

AU - Quiros, J. Ramón

AU - Saieva, Calogero

AU - Skeie, Guri

AU - Steffen, Annika

AU - Stepien, Magdalena

AU - Tjønneland, Anne

AU - Trichopoulou, Antonia

AU - Tumino, Rosario

AU - Van Der Schouw, Yvonne T.

AU - Verschuren, W. M.Monique

AU - Langenberg, Claudia

AU - Di Angelantonio, Emanuele

AU - Riboli, Elio

AU - Wareham, Nicholas J.

AU - Danesh, John

AU - Butterworth, Adam S.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Adiposity

KW - Coronary heart disease

KW - Epidemiology

KW - Metabolic syndrome

KW - Obesity

U2 - 10.1093/eurheartj/ehx448

DO - 10.1093/eurheartj/ehx448

M3 - Journal article

C2 - 29020414

AN - SCOPUS:85044078598

SN - 0195-668X

VL - 39

SP - 397

EP - 406

JO - European Heart Journal

JF - European Heart Journal

IS - 5

ER -

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

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