title: Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.
abstract: BACKGROUND
  Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients.
  
  
  RESULTS
  The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients.
  
  
  CONCLUSIONS
  Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients.
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Farré
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Universitat Pompeu Fabra, School of Medicine, Spain; Universitat Autònoma de Barcelona, School of Medicine, Spain.
authors.forename: Júlia
authors.initials: J
authors.lastname: Aranyó
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, School of Medicine, Spain; Universitat Autònoma de Barcelona, School of Medicine, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Enjuanes
authors.affiliation: Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, School of Medicine, Spain; Universitat Autònoma de Barcelona, School of Medicine, Spain; Jordi Gol Primary Care Research Institute. Catalan Institute of Heath, Barcelona (Spain).
authors.forename: José María
authors.initials: JM
authors.lastname: Verdú-Rotellar
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ruiz
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Gina
authors.initials: G
authors.lastname: Gonzalez-Robledo
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Oona
authors.initials: O
authors.lastname: Meroño
authors.affiliation: Laboratori de Referència de Catalunya, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: de Ramon
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, School of Medicine, Spain; Universitat Autònoma de Barcelona, School of Medicine, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Moliner
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruguera
authors.affiliation: Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; Heart Diseases Biomedical Research Group, Program of Research in Inflammatory and Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Universitat Pompeu Fabra, School of Medicine, Spain; Universitat Autònoma de Barcelona, School of Medicine, Spain. Electronic address: josepcomin@gmail.com.
authors.forename: Josep
authors.initials: J
authors.lastname: Comin-Colet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D009765:Obesity / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013030:Spain; D016019:Survival Analysis; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology
chemical_list: D009638:Norepinephrine
keywords: Body mass index; Chronic heart failure; Norepinephrine; Obesity