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

Lassale, Camille; Tzoulaki, Ioanna; Moons, Karel G.M.; Sweeting, Michael; Boer, Jolanda M. A.; Johnson, Laura; Huerta, José María; Agnoli, Claudia; Freisling, Heinz; Weiderpass, Elisabete; Wennberg, Patrik; A, Daphne L. van der; Arriola, Larraitz; Benetou, Vassiliki; Boeing, Heiner; Bonnet, Fabrice; Colorado‐Yohar, Sandra; Engström, Gunnar; Eriksen, Anne Kirstine; 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; Stępień, Magdalena; Tjønneland, Anne; Trichopoulou, Antonia; Tumino, Rosario; Schouw, Yvonne T. van der; Verschuren, W M Monique; Langenberg, Claudia; Angelantonio, Emanuele Di; Riboli, Elio; Wareham, Nicholas J.; Danesh, John; Butterworth, Adam S.

doi:10.1093/eurheartj/ehx448

Cited by 240 publications

(176 citation statements)

References 60 publications

(66 reference statements)

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“…Numerous prospective cohort studies have previously investigated the association between MHO phenotype and CVDs risk as a composite outcome (7,9,11,12,13,14,15,16,25,34,39,40), whereas specific outcomes, such as MI were limited. Our results were also consistent with those of recent meta-analyses showing that MHO individuals were at increased risk for cardiovascular events over a long-term follow-up (41).…”

Section: Discussionmentioning

confidence: 99%

“…Previous prospective cohort studies have demonstrated that MHO individuals are at an increased risk of CVDs and all-cause mortality compared with metabolically healthy normal weight (MH-NW) individuals (7,9,11,12,13,14,15). For example, a recent large-scale study investigating a 30-year follow-up period in 90 257 women found that the MHO group had an increased 1.44-fold risk of MI, 1.37-fold risk of stroke and 1.39-fold risk of CVDs (15).…”

Section: Introductionmentioning

confidence: 99%

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Association between the metabolically healthy obese phenotype and the risk of myocardial infarction: results from the Kailuan study

Wang

et al. 2018

European Journal of Endocrinology

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Objective: This study aimed to determine if the metabolically healthy obese (MHO) is associated with an increased risk of myocardial infarction (MI) in Chinese population. Design: The Kailuan study is a community-based prospective cohort study. Methods: BMI and metabolic syndrome (MetS) were assessed in 91 866 participants without a history of MI or stroke. Participants were categorised into six mutually exclusive groups according to the BMI-MetS status: normal weight (BMI: ≤ 18.5to < 24.0 kg/m 2 ) without MetS (MH-NW), normal weight with MetS (MUH-NW), overweight (BMI: ≤ 24.0to < 28.0 kg/m 2 ) without MetS (MH-OW), overweight with MetS (MUH-OW), obese (BMI ≥ 28.0 kg/m 2 ) without MetS (MHO) and obese with MetS (MUO). The hazard ratio (HR) with 95% CI was calculated for the incidence of MI using a multivariable Cox model. Results: A total of 6745 (7.34%) individuals were classified as MHO. During a median 8-year follow-up, 1167 (1.27%) participants developed MI. The MHO group had an increased risk of MI (HR: 1.76, 95% CI: 1.37-2.25) in comparison with the MH-NW group after adjusting for potential confounding variables. After a similar adjustment, the risk of MI was significantly elevated in the MUH-NW (HR: 1.62, 95% CI: 1.28-2.05), MUH-OW (HR: 1.98, 95% CI: 1.67-2.35) and MUO group (HR: 2.06, 95% CI: 1.70-2.49). Conclusions: MHO subjects showed a substantially higher risk of MI in comparison with MH-NW subjects. That said, even without measurable metabolic abnormalities, obesity was associated with a higher risk of MI. European Journal of Endocrinology179:6 349 Clinical Study Y Xu, H Li and others MHO and MI https://eje.bioscientifica.com 1.17 (0.68-2.00) 1.42 (0.97-2.08) 1.77 (1.17-2.68) † P for heterogeneity was attained from the likelihood ratio test.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between the metabolically healthy obese phenotype and the risk of myocardial infarction: results from the Kailuan study

Wang

et al. 2018

European Journal of Endocrinology

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“…In addition to BMI, the criteria used to define subgroups in the context of metabolic health is frequently based on: (1) the absence/ presence of the metabolic syndrome; and (2) insulin sensitivity. Interestingly, findings from several meta-analyses [8][9][10][11] and recent large-scale cohort studies [12][13][14] do not clearly support the notion that MHO subgroups, as currently defined, are protected from cardiometabolic complications ( Table 1).…”

Section: Evidence For An Mho Phenotypementioning

confidence: 95%

“…However, among individuals with CVD events, the metabolic syndrome has been found to be present in a much smaller fraction of individuals with normal weight as compared with overweight and obese individuals. As an example, in the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD) study, only 20% of incident CVD cases among normal-weight participants were observed in those with the metabolic syndrome at baseline; this is a considerably smaller proportion than in overweight (52%) and obese (76%) individuals [14]. This clearly points towards variation in the sensitivity of the metabolic syndrome to predict future CVD cases across the BMI range; its absence is unlikely to rule out CVD risk in normal-weight individuals.…”

Section: The Muhnw Phenotypementioning

confidence: 99%

Metabolic health in normal-weight and obese individuals

Schulze

2018

Diabetologia

135

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Cardiovascular complications are commonly associated with obesity. However, a subgroup of obese individuals may not be at an increased risk for cardiovascular complications; these individuals are said to have metabolically healthy obesity (MHO). In contrast, metabolically unhealthy individuals are at high risk of cardiovascular disease (CVD), irrespective of BMI; thus, this group can include individuals within the normal weight category (BMI 18.5-24.9 kg/m 2 ). This review provides a summary of prospective studies on MHO and metabolically unhealthy normal-weight (MUHNW) phenotypes. Notably, there is ongoing dispute surrounding the concept of MHO, including the lack of a uniform definition and the potentially transient nature of metabolic health status. This review highlights the relevance of alternative measures of body fatness, specifically measures of fat distribution, for determining MHO and MUHNW. It also highlights alternative approaches of risk stratification, which account for the continuum of risk in relation to CVD, which is observable for most risk factors. Moreover, studies evaluating the transition from metabolically healthy to unhealthy phenotypes and potential determinants for such conversions are discussed. Finally, the review proposes several strategies for the use of epidemiological research to further inform the current debate on metabolic health and its determination across different stages of body fatness.

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“…Early reports suggested that individuals with MHO were not at increased risk of CVD compared with individuals with metabolically healthy normal weight (4,5). However, several recent prospective cohort studies have found an increased CVD risk associated with MHO (3,(27)(28)(29)(30)(31)(32). A prospective cohort study in the U.K. consisting of 3.5 million adults with a median follow-up time of 5.4 years showed that MHO was associated with CVD compared with metabolically healthy normal weight (30).…”

Section: Comparison With Other Studiesmentioning

confidence: 99%

Metabolically Healthy Obesity and High Carotid Intima-Media Thickness in Children and Adolescents: International Childhood Vascular Structure Evaluation Consortium

Zhao

López‐Bermejo

Caserta³

et al. 2018

Diabetes Care

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OBJECTIVEIt has been argued that metabolically healthy obesity (MHO) does not increase cardiovascular disease (CVD) risk. This study examines the association of MHO with carotid intima-media thickness (cIMT), a proxy of CVD risk, in children and adolescents. RESEARCH DESIGN AND METHODSData were available for 3,497 children and adolescents aged 6-17 years from five population-based cross-sectional studies in Brazil, China, Greece, Italy, and Spain. Weight status categories (normal, overweight, and obese) were defined using BMI cutoffs from the International Obesity Task Force. Metabolic status (defined as "healthy" [no risk factors] or "unhealthy" [one or more risk factors]) was based on four CVD risk factors: elevated blood pressure, elevated triglyceride levels, reduced HDL cholesterol, and elevated fasting glucose. High cIMT was defined as cIMT ‡90th percentile for sex, age, and study population. Logistic regression model was used to examine the association of weight and metabolic status with high cIMT, with adjustment for sex, age, race/ethnicity, and study center. RESULTSIn comparison with metabolically healthy normal weight, odds ratios (ORs) for high cIMT were 2.29 (95% CI 1.58-3.32) for metabolically healthy overweight and 3.91 (2.46-6.21) for MHO. ORs for high cIMT were 1.44 (1.03-2.02) for unhealthy normal weight, 3.49 (2.51-4.85) for unhealthy overweight, and 6.96 (5.05-9.61) for unhealthy obesity. CONCLUSIONSAmong children and adolescents, cIMT was higher for both MHO and metabolically healthy overweight compared with metabolically healthy normal weight. Our findings reinforce the need for weight control in children and adolescents irrespective of their metabolic status.

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

Cited by 240 publications

References 60 publications

Association between the metabolically healthy obese phenotype and the risk of myocardial infarction: results from the Kailuan study

Association between the metabolically healthy obese phenotype and the risk of myocardial infarction: results from the Kailuan study

Metabolic health in normal-weight and obese individuals

Metabolically Healthy Obesity and High Carotid Intima-Media Thickness in Children and Adolescents: International Childhood Vascular Structure Evaluation Consortium

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