Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification

Ralf Koos; Thilo Krueger; Ralf Westenfeld; Harald Peter Kühl; Vincent Brandenburg; Andreas Horst Mahnken; Sven Stanzel; Cees Vermeer; Ellen C. M. Cranenburg; Jürgen Floege; Malte Kelm; Leon J. Schurgers

doi:10.1160/TH08-09-0611

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(04): 706-713
DOI: 10.1160/TH08-09-0611

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification

Ralf Koos

¹Department of Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Thilo Krueger

²Department of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Ralf Westenfeld

¹Department of Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Harald Peter Kühl

¹Department of Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Vincent Brandenburg

²Department of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Andreas Horst Mahnken

³Department of Diagnostic Radiology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Sven Stanzel

⁴Institute of Medical Statistics, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Cees Vermeer

⁵VitaK and Cardiovascular Research Institute CARIM, Maastricht University, Maastricht, The Netherlands

,

Ellen C. M. Cranenburg

⁵VitaK and Cardiovascular Research Institute CARIM, Maastricht University, Maastricht, The Netherlands

,

Jürgen Floege

²Department of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Malte Kelm

¹Department of Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany

,

Leon J. Schurgers

⁵VitaK and Cardiovascular Research Institute CARIM, Maastricht University, Maastricht, The Netherlands

› Author Affiliations

Abstract

Summary

Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 ± 123.1 nM) compared to the control group (571.6 ± 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.

Keywords

Oral anticoagulation - aortic valve calcification - protein function - imaging - matrix Gla protein

Full Text

References

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