Metabolically healthy obesity is not a harmless condition

Chang Y, Kim BK, Yun KE et al.
J Am Coll Cardiol. 2014 Apr 17. doi: 10.1016/j.jacc.2014.03.042

Background

The effect of obesity on cardiovascular disease (CVD) is mediated through metabolic abnormalities such as dyslipidaemia, hyperglycaemia and hypertension [1,2]. Not all obese individuals are affected by obesity-related metabolic disturbances [3-5]. Metabolically healthy obese (MHO) are relatively insulin sensitive [6]. It is a topic of debate whether MHO is associated with excess CV risk. Importantly, a substantial subset of MHO individuals develop adverse metabolic changes over time, associated with obesity [7,8].
Coronary artery calcification (CAC) scores reflect the long term impact of elevated CVD risk factors and are an independent predictor of subclinical atherosclerosis [9]. This study examines CAC scores in MHO and metabolically healthy normal weight individuals in an apparently healthy Korean population who participated in a health screening exam program. MHO was defined as the absence of any components of the metabolic syndrome or insulin resistance [4].

Main results

• In multivariable models, CAC score ratio of MHO as compared to normal weight participants was 2.26 (95%CI: 1.48-3.43). Prevalance ratios for CAC score 1-80 was 1.38 (95%CI: 1.15-1.66) and 1.70 (95%CI: 1.12-2.61) for CAC score >80.
• Overweight participants showed a nonsignificant increase in the prevalence of coronary calcification (CAC score ratio: 1.21, 95%CI: 0.80-1.84, prevalence ratio’s: CAC 1-80: 1.09, 95%CI: 0.91-1.31, and CAC > 80: 1.09, 95%CI: 0.70-1.68).
• Adjustment for metabolic risk factors associated with obesity slightly reduced the associations, but they remained statistically significant. Further adjustment for LDL-c levels markedly attenuated the association between MHO and CAC score, after which it was no longer statistically significant.

Conclusion

This study in metabolically healthy Korean men and women shows that MHO individuals had a higher prevalence of subclinical coronary atherosclerosis compared to participants of normal weight. Thus, MHO is not a harmless condition.
After correction for LDL-cholesterol levels and metabolic risk factors, the association was attenuated and no longer statistically significant. All participants had healthy levels of metabolic risk factors. This implies that the association between MHO and subclinical atherosclerosis is mediated by metabolic risk factors at levels below those considered aberrant. Many studies addressing MHO did not address LDL-c. The label of metabolically healthy for obese persons may therefore be an artifact of the cut-off levels used and the choice of factors included in the definition of metabolic health.

Editorial comment [10]

“This study casts serious doubt on the concept of obese individuals maintaining a benign prognosis, and highlight the fact that obesity per se is a genuine disease. It also seriously questions the fundamental concept of the need to define a subset of obese individuals as ‘metabolically healthy.’ Is there a compelling clinical and practical reason for doing so? By labeling a subset of obese individuals as ‘metabolically healthy’ would undermine the ultimate task that physicians and health organizations face, to curb the current obesity epidemic and prevent the next generation of individuals from becoming obese. We must simply accept obesity as a disease, and consider no level of obesity to be healthy. The analysis by Chang and colleagues strengthens the argument that ‘healthy obesity’ is simply a myth.”

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