Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population

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Abstract

Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP ( 671 pmol l−1) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17–2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.

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Acknowledgements

The clinical part of the project was supported by the Internal Grant Agency of Czech Ministry of Health (NT13186) and by the Charles University Research Fund (project number P36). We are grateful to IDS Plc., providing free of charge, newly developed kits for estimation of dp-ucMGP. We would like to acknowledge the hard work of all investigators in the Czech Republic who participated in the post-MONICA project, and last but not least all laboratory technicians, realizing extent laboratory assessments for the present study.

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Correspondence to O Mayer Jr.

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Mayer Jr, O., Seidlerová, J., Wohlfahrt, P. et al. Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population. J Hum Hypertens 30, 418–423 (2016). https://doi.org/10.1038/jhh.2015.55

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