The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease.

Abstract

BACKGROUND:

Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylated MGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk.

METHODS:

We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays.

RESULTS:

Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP ≥ 977 pmol/L or t-ucMGP ≤ 2825 nmol/L) were all identified as robust predictors of all-cause 5-year mortality. However, their co-incidence represented a substantial additional risk. We observed the highest mortality risk in patients with elevated BNP plus high dp-ucMGP compared to those with normal BNP plus low dp-ucMGP; fully adjusted HRR's were 4.86 (3.15-7.49). Likewise, the risk was increased when compared with patients with elevated BNP plus low dp-ucMGP; HRR 2.57 (1.60-4.10). Similar result we observed when co-incidence of elevated BNP and low t-ucMGP was analyzed [corresponding HRR's were 4.16 (2.62-6.61) and 1.96 (1.24-3.12)].

CONCLUSIONS:

The concomitant abnormality of uncarboxylated MGP and mild elevation of BNP leads in chronic patients with vascular disease to about two-fold increase of the relative mortality risk. We hypothesize that abnormal homeostasis of MGP is involved in the pathophysiology of HF.

• Authors: Otto Mayer Jr, Jitka Seidlerová, Jiří Vaněk, Petra Karnosová, Jan Bruthans, Jan Filipovský, Peter Wohlfahrt, Renata Cífková, Jindra Windrichová, Marjo H J Knapen, Nadja E A Drummen, Cees Vermeer
• Journal: International journal of cardiology (Int J Cardiol) Vol. 203 Pg. 916-22 (Jan 15 2016) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 26618253 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

• Aged
• Biomarkers (blood)
• Calcinosis
• Calcium-Binding Proteins (blood)
• Czech Republic (epidemiology)
• Extracellular Matrix Proteins (blood)
• Female
• Follow-Up Studies
• Heart Failure (blood, complications, mortality)
• Humans
• Male
• Prospective Studies
• Risk Assessment
• Risk Factors
• Survival Rate (trends)
• Vascular Diseases (blood, complications, mortality)
• Vitamin K