title: Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients.
abstract: OBJECTIVE
  To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients.
  
  
  METHODS
  EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes-CHD, peripheral arterial disease (PAD), heart failure, and stroke-were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD.
  
  
  RESULTS
  During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06-1.38), PAD (HRSD 1.32 [95% CI 1.07-1.65]), and heart failure (HRSD 1.75 [95% CI 1.42-2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94-1.34]) or stroke (HRSD 1.05 [95% CI 0.73-1.49]). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes.
  
  
  CONCLUSIONS
  High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.
authors.affiliation: Corresponding author: Geertje W. Dalmeijer, g.w.dalmeijer@umcutrecht.nl.
authors.forename: Geertje W
authors.initials: GW
authors.lastname: Dalmeijer
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: Elke J
authors.initials: EJ
authors.lastname: Magdeleyns
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: W M Monique
authors.initials: WM
authors.lastname: Verschuren
authors.forename: Jolanda M A
authors.initials: JM
authors.lastname: Boer
authors.forename: Joline W J
authors.initials: JW
authors.lastname: Beulens
mesh_terms: D002135:Calcium-Binding Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D014812:Vitamin K / Q000378:metabolism; D049629:Waist-Hip Ratio; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein