Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease

Otto, Jr. Mayer*, Jitka Seidlerova, Jan Bruthans, Jan Filipovsky, Katarina Timoracka, Jiri Vanek, Lenka Cerna, Peter Wohlfahrt, Renata Cifkova, Elke Theuwissen, Cees Vermeer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease. Materials and methods: We examined 799 patients (mean age 65.1 +/- 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK). Results: During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (>= 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32-2.72) and 1.88 (95% CI, 1.22-2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18-2.61) and 1.79 (95% CI, 1.12-2.57). Conclusions: In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.
Original languageEnglish
Pages (from-to)162-168
JournalAtherosclerosis
Volume235
Issue number1
DOIs
Publication statusPublished - Jul 2014

Keywords

  • Matrix Gla-protein
  • Dp-ucMGP
  • Dp-cMGP
  • Mortality
  • Coronary heart disease
  • Stroke
  • Secondary prevention
  • EUROASPIRE

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