title: The Heart Failure Overweight/Obesity Survival Paradox: The Missing Sex Link.
abstract: OBJECTIVE
  This study sought to determine whether body mass index (BMI) has a differential impact on survival for females versus males with advanced systolic heart failure (HF).
  
  
  BACKGROUND
  Females have a survival advantage in HF, the mechanisms of which are unclear. There is also a proposed "obesity survival paradox" in which excess adiposity promotes HF survival.
  
  
  METHODS
  We reviewed 3,811 patients with left ventricular ejection fraction ≤40% who had undergone cardiopulmonary exercise testing between 1995 and 2011. The endpoint was all-cause mortality. Multivariable analysis was performed using a Cox proportional hazards model. Because of the nonlinearity of BMI, a restricted cubic spline was used. An interaction term was added to investigate the impact of BMI on mortality by sex.
  
  
  RESULTS
  The unadjusted data demonstrated an overall obesity survival paradox in HF. This survival paradox disappeared for males after adjustment for potential confounders, with overweight and obese males showing higher adjusted mortality hazard ratios compared with normal weight males. Conversely, females in the overweight BMI range (25.0 to 29.9 kg/m(2)) had the lowest adjusted mortality (hazard ratio: 0.84; 95% confidence interval: 0.77 to 0.93; p = 0.0005 compared with normal weight females) with a nadir in mortality hazard just below BMI 30 kg/m(2). The multivariable model supported a differential impact of BMI on mortality in males versus females (p for interaction <0.0001).
  
  
  CONCLUSIONS
  In this advanced HF cohort, an unadjusted obesity survival paradox disappeared after adjustment for confounders. Overweight and obese males had higher adjusted mortality than normal weight males, whereas a BMI in the overweight range was associated with a significant survival benefit in females.
authors.affiliation: Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Vest
authors.affiliation: Department of Mathematics, Cleveland State University, Cleveland, Ohio.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Section of Cardiovascular Imaging, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rory
authors.initials: R
authors.lastname: Hachamovitch
authors.affiliation: Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.affiliation: Section of Preventative Cardiology and Rehabilitation, Cleveland Clinic, Cleveland, Ohio. Electronic address: chol@ccf.org.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000401:mortality*; D050177:Overweight / Q000150:complications / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D013318:Stroke Volume; D016019:Survival Analysis
keywords: female; gender; heart failure; obesity; overweight