Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review

BACKGROUND: A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. METHODS: Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. RESULTS: A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define “metabolically healthy”, while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. CONCLUSIONS: MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.