title: The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.
abstract: BACKGROUND
  In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)).
  
  
  METHODS
  A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups.
  
  
  RESULTS
  BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35.
  
  
  CONCLUSIONS
  In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Padwal
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: F A
authors.initials: FA
authors.lastname: McAlister
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: J J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Faculty of Medicine, National Heart and Lung Institute, Imperial College London (Royal Brompton Hospital), London, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Cowie
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rich
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: ANMCO Research Center, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maggioni
authors.affiliation: Department of Medicine and National Institute for Health Innovation, University of Auckland, Auckland, New Zealand.
authors.forename: G
authors.initials: G
authors.lastname: Gamble
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ariti
authors.affiliation: Department of Medicine and National Institute for Health Innovation, University of Auckland, Auckland, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Earle
authors.affiliation: Faculty of Social and Health Sciences, UNITEC Institute of Technology, Auckland, New Zealand.
authors.forename: G
authors.initials: G
authors.lastname: Whalley
authors.affiliation: Department of Medicine and National Institute for Health Innovation, University of Auckland, Auckland, New Zealand.
authors.forename: K K
authors.initials: KK
authors.lastname: Poppe
authors.affiliation: Department of Medicine and National Institute for Health Innovation, University of Auckland, Auckland, New Zealand.
authors.forename: R N
authors.initials: RN
authors.lastname: Doughty
authors.affiliation: Department of Medicine, Hospital Universitari Germans Trias i Pujol UAB, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Bayes-Genis
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015897:Comorbidity; D005260:Female; D006333:Heart Failure / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D008297:Male; D009765:Obesity / Q000150:complications / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013318:Stroke Volume; D016019:Survival Analysis