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

Atherosclerosis. 2014 Jul;235(1):162-8. doi: 10.1016/j.atherosclerosis.2014.04.027. Epub 2014 May 6.

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.

Keywords: Coronary heart disease; Dp-cMGP; Dp-ucMGP; EUROASPIRE; Matrix Gla-protein; Mortality; Secondary prevention; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Calcium-Binding Proteins / chemistry
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / blood*
  • Extracellular Matrix Proteins / chemistry
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / mortality
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / mortality
  • Myocardial Revascularization / mortality
  • Proportional Hazards Models
  • Prospective Studies
  • Regression Analysis
  • Stroke / blood*
  • Stroke / mortality
  • Treatment Outcome
  • Vascular Diseases / blood*
  • Vascular Diseases / mortality*
  • Vitamin K / metabolism

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Vitamin K