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Multicenter Study
. 2016 Jan 15:203:916-22.
doi: 10.1016/j.ijcard.2015.10.226. Epub 2015 Oct 31.

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

Otto Mayer Jr  1 , Jitka Seidlerová  2 , Jiří Vaněk  3 , Petra Karnosová  2 , Jan Bruthans  4 , Jan Filipovský  2 , Peter Wohlfahrt  5 , Renata Cífková  5 , Jindra Windrichová  6 , Marjo H J Knapen  7 , Nadja E A Drummen  7 , Cees Vermeer  7
Affiliations
Multicenter Study

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

Otto Mayer Jr et al. Int J Cardiol. .

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.

Keywords: Atherovascular disease; Heart failure; Matrix γ-carboxyl glutamate protein (MGP); Mortality; dp-ucMGP; t-ucMGP.

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