title: Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease.
abstract: OBJECTIVE
  Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals.
  
  
  METHODS
  The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data.
  
  
  METHODS
  Incidence of CVD.
  
  
  RESULTS
  After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD.
  
  
  CONCLUSIONS
  Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Royal FrieslandCampina, Amersfoort, The Netherlands. Electronic address: ellen.vandenheuvel@frieslandcampina.com.
authors.forename: Ellen G H M
authors.initials: EG
authors.lastname: van den Heuvel
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: Nm.vanschoor@vumc.nl.
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine and Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: P.lips@vumc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.affiliation: VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: e.magdeleyns@vitak.com.
authors.forename: Elke J P
authors.initials: EJ
authors.lastname: Magdeleyns
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: djh.deeg@vumc.nl.
authors.forename: Dorly J H
authors.initials: DJ
authors.lastname: Deeg
authors.affiliation: VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. Electronic address: c.vermeer@vitak.com.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine and Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. Electronic address: M.denHeijer@vumc.nl.
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
mesh_terms: D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012307:Risk Factors; D014813:Vitamin K Deficiency / Q000097:blood* / Q000150:complications; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein
keywords: CVD; Cardiovascular disease; Gla; LASA; Longitudinal Aging Study Amsterdam; MGP; Matrix Gla-protein; Vitamin K status; cardiovascular events and disease; desphospho-carboxylated MGP; desphospho-uncarboxylated MGP; dp-cMGP; dp-ucMGP; matrix Gla protein; γ-carboxyglutamate