title: Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure.
abstract: We recently demonstrated that circulating MGP [matrix Gla (γ-carboxylated glutamate) protein] levels were associated with left ventricular dysfunction and increased mortality in patients with symptomatic aortic stenosis. We hypothesized that patients with chronic HF (heart failure) would have dysregulated MGP levels. We examined plasma dp-cMGP (non-phosphorylated carboxylated MGP) and dp-ucMGP (non-phosphorylated undercarboxylated MGP) in 179 patients with chronic HF and matched healthy controls as well as the relationship between MGP and cardiac dysfunction as assessed by echocardiographic measurements, inflammation [CRP (C-reactive protein)] and neurohormonal activation [NT-proBNP (N-terminal proB-type natriuretic peptide)] and the prognostic value of MGP levels in relation to mortality in these patients. We found markedly enhanced plasma dp-cMGP and, in particular, of dp-ucMGP in chronic HF with increasing levels with disease severity. Elevated MGP species were associated with ischaemic aetiology, increased CRP and NT-proBNP levels, as well as systolic and diastolic dysfunction. Finally, dp-ucMGP was associated with long-term heart transplant-free survival (n=48) in univariate, but not in multivariate, analysis. However, plasma dp-ucMGP was markedly higher in patients who died because of progression of HF (n=12) and gave prognostic information also in multivariate analysis. In conclusion, a dysregulated MGP system could be involved in left ventricular dysfunction in patients with chronic HF.
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. thor.ueland@medisin.uio.no
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.forename: Rita
authors.initials: R
authors.lastname: Skårdal
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
mesh_terms: D000328:Adult; D000368:Aged; D002114:Calcinosis; D002135:Calcium-Binding Proteins / Q000097:blood*; D002908:Chronic Disease; D018450:Disease Progression; D004452:Echocardiography / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012044:Regression Analysis; D016277:Ventricular Function, Left / Q000502:physiology; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein