title: The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness.
abstract: OBJECTIVE
  Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality.
  
  
  RESULTS
  Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥ 25 or ≥ 30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30-50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.
  
  
  CONCLUSIONS
  (i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
authors.affiliation: Unit for Preventive Nutrition, Department of Biosciences and Nutrition at NOVUM,  Karolinska Institutet, 14157, Huddinge, Stockholm,  Sweden.
authors.forename: Francisco B
authors.initials: FB
authors.lastname: Ortega
authors.forename: Duck-Chul
authors.initials: DC
authors.lastname: Lee
authors.forename: Peter T
authors.initials: PT
authors.lastname: Katzmarzyk
authors.forename: Jonatan R
authors.initials: JR
authors.lastname: Ruiz
authors.forename: Xuemei
authors.initials: X
authors.lastname: Sui
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Church
authors.forename: Steven N
authors.initials: SN
authors.lastname: Blair
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D005080:Exercise Test; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000401:mortality* / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D010641:Phenotype; D010809:Physical Fitness / Q000502:physiology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors