title: The association between uncarboxylated matrix Gla protein and lipoprotein-associated phospholipase A2.
abstract: BACKGROUND
  Lipoprotein-associated phospholipase A2 (Lp-PLA2) is independently associated with cardiovascular risk, probably via inflammatory activity in sclerotic plaque. We speculated whether Lp-PLA2 has a role in the aetiology of vascular calcifications, estimated from circulating uncarboxylated matrix Gla protein (MGP) species and whether we could find a potential interaction of Lp-PLA2 and MGP in terms of mortality.
  
  
  METHODS
  We examined 798 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays, developed by VitaK (Maastricht, The Netherland)
  
  
  RESULTS
  Lp-PLA2 activity was independently positively associated with desphospho-uncarboxylated MGP (dp-ucMGP) [β coeff = 0.098, p=0.006]. 1SD of Lp-PLA2 activity was associated with 37% increased risk (p=0.001) of elevated dp-ucMGP (≥977 pmol/L, top quartile). In the Cox proportional hazard model adjusted for conventional risk factors, the patients in the highest quartile of dp-ucMGP or lowest quintile of total-uncarboxylated ucMGP (<2660 nmol/L) had higher risk of all-cause mortality [HRR 2.79 (95% CI 1.97-3.94) and HRR 1.69 (95% CI 1.18-2.42), respectively]. We observed no effect of high Lp-PLA2 activity (≥195 nmol/min/mL) on total mortality.
  
  
  CONCLUSIONS
  We assume that Lp-PLA2 is involved in vascular calcification and that dp-ucMGP is a more appropriate biomarker of residual risk than Lp-PLA2 itself.
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: Department of Neurology, University Hospital, Pilsen, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Kielbergerová
authors.affiliation: 2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Centre for Cardiovascular Prevention of the 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: Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlfahrt
authors.affiliation: Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Brno, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Cífková
authors.affiliation: Department of Clinical Biochemistry and Hematology, University Hospital Pilsen, Pilsen, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Trefil
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Marjo H J
authors.initials: MH
authors.lastname: Knapen
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Nadja E A
authors.initials: NE
authors.lastname: Drummen
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002135:Calcium-Binding Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D000097568:Matrix Gla Protein
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein
keywords: Coronary heart disease; Euroaspire; Lipoprotein-associated phospholipaseA(2); Matrix Gla protein; Mortality risk; Stroke