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

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.

• Authors: Otto Mayer Jr, Jitka Seidlerová, Jan Bruthans, Jan Filipovský, Katarina Timoracká, Jiří Vaněk, Lenka Cerná, Peter Wohlfahrt, Renata Cífková, Elke Theuwissen, Cees Vermeer
• Journal: Atherosclerosis (Atherosclerosis) Vol. 235 Issue 1 Pg. 162-8 (Jul 2014) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 24835435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

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