title: Adiponectin in chronic heart failure: influence of diabetes and genetic variants.
abstract: BACKGROUND
  We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.
  
  
  METHODS
  Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.
  
  
  RESULTS
  Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).
  
  
  CONCLUSIONS
  Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.
authors.affiliation: Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. serge.masson@marionegri.it
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Francesca
authors.initials: F
authors.lastname: Gori
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Valentina
authors.initials: V
authors.lastname: Milani
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Luisa
authors.initials: L
authors.lastname: Crociati
authors.forename: Silvia
authors.initials: S
authors.lastname: Pietri
authors.forename: Tarcisio
authors.initials: T
authors.lastname: Vago
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Franzosi
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D052242:Adiponectin