title: The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease.
abstract: BACKGROUND
  Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylated MGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk.
  
  
  METHODS
  We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays.
  
  
  RESULTS
  Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP ≥ 977 pmol/L or t-ucMGP ≤ 2825 nmol/L) were all identified as robust predictors of all-cause 5-year mortality. However, their co-incidence represented a substantial additional risk. We observed the highest mortality risk in patients with elevated BNP plus high dp-ucMGP compared to those with normal BNP plus low dp-ucMGP; fully adjusted HRR's were 4.86 (3.15-7.49). Likewise, the risk was increased when compared with patients with elevated BNP plus low dp-ucMGP; HRR 2.57 (1.60-4.10). Similar result we observed when co-incidence of elevated BNP and low t-ucMGP was analyzed [corresponding HRR's were 4.16 (2.62-6.61) and 1.96 (1.24-3.12)].
  
  
  CONCLUSIONS
  The concomitant abnormality of uncarboxylated MGP and mild elevation of BNP leads in chronic patients with vascular disease to about two-fold increase of the relative mortality risk. We hypothesize that abnormal homeostasis of MGP is involved in the pathophysiology of HF.
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic. Electronic address: mayero@fnplzen.cz.
authors.forename: Otto
authors.initials: O
authors.lastname: Mayer
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Seidlerová
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vaněk
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Karnosová
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Bruthans
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Filipovský
authors.affiliation: First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlfahrt
authors.affiliation: First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Cífková
authors.affiliation: Department of Immunodiagnostics, University Hospital, Pilsen, Czech Republic.
authors.forename: Jindra
authors.initials: J
authors.lastname: Windrichová
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: Marjo H J
authors.initials: MH
authors.lastname: Knapen
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: Nadja E A
authors.initials: NE
authors.lastname: Drummen
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis; D002135:Calcium-Binding Proteins / Q000097:blood*; D018153:Czech Republic / Q000453:epidemiology; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000401:mortality*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D014652:Vascular Diseases / Q000097:blood / Q000150:complications* / Q000401:mortality; D014812:Vitamin K; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein
keywords: Atherovascular disease; Heart failure; Matrix γ-carboxyl glutamate protein (MGP); Mortality; dp-ucMGP; t-ucMGP