title: Association of ficolin-3 with severity and outcome of chronic heart failure.
abstract: BACKGROUND
  Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.
  
  
  RESULTS
  MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.
  
  
  CONCLUSIONS
  This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.
authors.affiliation: IIIrd Department of Internal Medicine, Semmelweis University, and Research Group of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Timea
authors.initials: T
authors.lastname: Gombos
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Förhécz
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Pozsonyi
authors.forename: Alice
authors.initials: A
authors.lastname: Gustavsen
authors.forename: Lívia
authors.initials: L
authors.lastname: Jánoskuti
authors.forename: István
authors.initials: I
authors.lastname: Karádi
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.forename: Erik T
authors.initials: ET
authors.lastname: Askevold
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000368:Aged; D002908:Chronic Disease; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000276:immunology / Q000401:mortality; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D000097604:Ficolins
chemical_list: D003176:Complement C3; D006023:Glycoproteins; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C109662:FCN3 protein, human