The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: A meta-analysis of individual patient data

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) X30 kgm 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)). PATIENTS AND 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: o22.5, 22.5–24.9 (referent), 25–29.9, 30–34.9 and X35 kgm 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 kgm 2, the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)¼1.31 (95% confidence interval¼1.15–1.50) for BMI o22.5, 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 X35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval¼0.80–1.57) for BMI o22.5, 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 X35. 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 kgm 2.