Obesity without metabolic abnormalities still associated with increased CV risk

25-9-2017 • Caleyachetty R et al., J Am Coll Cardiol 2017  

Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women

Caleyachetty R, Thomas GN, PHD, Toulis KA, et al.
J Am Coll Cardiol 2017;70:142937

Introduction and Methods

“Metabolically healthy obese” (MHO) are a subset of obese individuals without obesity-related metabolic abnormalities [1,2]. Whether MHO is associated with excess risk of cardiovascular disease is unclear, because of the inconsistent definition of metabolic health across studies, and the limited data evaluating the association between MHO and cardiovascular events.
In this analysis, the associations among body size phenotypes with or without metabolic abnormalities and incident CHD, CVD, HF, and peripheral vascular disease (PVD) were evaluated, using electronic health records of 3.5 million individuals in The Health Improvement Network from 1995 to 2015 [3,4].
Participants were older than 18 years and had no history of a CVD event before study entry. The 3 metabolic abnormalities (MA) diabetes, hypertension, or hyperlipidemia were summed to create a MA score (0, 1, 2, and 3). Persons were divided into 14 body size phenotypes:
  • underweight with 0 MA or with ≥ 1 MA
  • normal weight with 0 or 1 or 2 or 3 MA
  • overweight with 0 or 1 or 2 or 3 MA
  • obese with 0 or 1 or 2 or 3 MA.
Endpoints were the first occurrence of CHD (angina, ischemic heart disease, MI) or CVD (TIA, ischemic stroke, hemorrhagic stroke), or HF, or PVD.

Main results

  • Among initially MH- overweight individuals, approximately 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension. Among individuals who were initially MHO, approximately 5.6% developed diabetes, 11.5% developed hyperlipidemia, and 10.5% developed hypertension.
Compared with normal weight individuals with 0 MA and after adjustment for potential confounders:
  • an increased risk of CHD was observed for overweight individuals with 0 MA (HR: 1.30; 95%CI: 1.27-1.34) and obese individuals with 0 MA (HR: 1.49; 95%CI: 1.45-1.54)
  • an increased risk of CVD was observed for underweight individuals with 0 MA (HR: 1.31; 95%CI: 1.23-1.40) and obese individuals with 0 MA (HR: 1.07; 95%CI: 1.04-1.11)
  • an increased risk of HF was observed for underweight individuals (HR: 1.36; 95%CI: 1.23-1.51), overweight individuals with 0 MA (HR: 1.11; 95%CI: 1.06-1.16) and obese individuals with 0 MA (HR: 1.96; 95%CI: 1.86-2.06)
  • a decreased risk of PVD was observed for overweight with 0 MA (HR: 0.92; 95%CI: 0.88-0.96) and obese individuals with 0 MA (HR: 0.91; 95% CI: 0.86 - 0.96)
  • The risk of CHD, CVD, PVD and HF in the normal weight, overweight, and obese groups increased with increased number of metabolic abnormalities.
  • Subgroup analyses showed that the CVD risk in overweight and obese individuals without MA, as well as the HF risk in overweight individuals without MA differed significantly by gender: females had stronger positive associations with CVD and HF compared with males.
  • Moreover, overweight and obese individuals without metabolic abnormalities aged <65 years had significantly stronger positive associations with CHD, CVD, HF, and PVD compared with individuals ≥ 65 years of age.


Individuals who are obese with no metabolic abnormalities are at higher risk of CHD, CVD, and HF, compared with normal weight metabolically healthy persons. On the other hand, normal weight individuals may be at high CV risk, if they have metabolic abnormalities.

Editorial comment [5]

In their editorial article, Bea and Sweitzer discuss the limitations of the analysis published by Caleyachtty et al, which include the following:
  • The data were extracted exclusively from 1 UK network, which does not give us information about various other populations.  
  • The BMI is not the ideal measure for fat.
  • The time variance of BMI and metabolic parameters was not assessed.
  • The influence of diet and physical activity was not evaluated.
Despite the limitations, the authors conclude as follows: ‘In conclusion, obesity increases cardiovascular risk regardless of metabolic status. However, metabolic dysfunction itself also carries risk independent of weight because of the similar results across BMI categories of CVD risk in the Caleyachetty et al. study, and others, when metabolic dysfunction is present. This study supports following the U.S. guidelines for screening of CVD in persons age older than 18 years, even perhaps extending screening, and acting upon findings that suggest metabolic risk to reduce cardiovascular morbidity and mortality.’
Find this article online at J Am Coll Cardiol


1. Rey-Lopez JP, de Rezende LF, de Sa TH, et al. Is the metabolically healthy obesity phenotype an irrelevant artifact for public health? Am J Epidemiol 2015;182:737–41.
2. Bradshaw PT, Stevens J. Invited commentary: limitations and usefulness of the metabolically healthy obesity phenotype. Am J Epidemiol 2015;182:742–4.
3. Blak BT, Thompson M, Dattani H, et al. Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care 2011;19:251–5.
4. Lewis JD, Schinnar R, Bilker WB, et al. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf 2007;16:393–401.
5. Bea JW, Sweitzer NK. More Appropriate Cardiovascular Risk Screening Through Understanding Complex Phenotypes: Mind the Gap. J Am Coll Cardiol 2017;70:1438-1440.

CVRMdiabeteshyperlipidemiahypertensionMetabolically healthy obeseobesityT2DM

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