title: HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin.
abstract: BACKGROUND
  Heart failure with reduced ejection fraction (HFrEF) exhibits a "reverse metabolic profile". Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.
  
  
  METHODS
  In patients with HFpEF(n=79), HFrEF(n=84), and controls(n=71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.
  
  
  RESULTS
  Leptin levels in HFpEF and HFrEF were increased (p<0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL.There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r=-0.364 p=0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p=0.044) but not in HFpEF. Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) μg/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p=0.310 but, compared to controls, higher levels in HFpEF (p=0.044) and HFrEF (p=0.001). Adiponectin correlated positively with NT-proBNP; r=0.396 p<0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p=0.045).
  
  
  CONCLUSIONS
  HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.
authors.affiliation: Department of Anesthesia and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Stockholm, Karolinska Institutet, Sweden. Electronic address: ulrikaljungfaxen@gmail.com.
authors.forename: Ulrika Ljung
authors.initials: UL
authors.lastname: Faxén
authors.affiliation: Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Hage
authors.affiliation: Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Andreasson
authors.affiliation: Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Donal
authors.affiliation: Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Daubert
authors.affiliation: Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.affiliation: Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010641:Phenotype; D013318:Stroke Volume / Q000502:physiology
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D020738:Leptin; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Adipocytokines; Adiponectin; Biomarker; Heart failure; Heart failure with preserved ejection fraction; Leptin