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
|