Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis

• Published in: Journal of internal medicine Vol. 268; no. 5; pp. 483 - 492
• Main Authors: Ueland, T., Gullestad, L., Dahl, C. P., Aukrust, P., Aakhus, S., Solberg, O. G., Vermeer, C., Schurgers, L. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Blackwell
• Subjects: Aged; Aged, 80 and over; all‐cause mortality; Anticoagulants - therapeutic use; Aorta - diagnostic imaging; Aorta - pathology; aortic stenosis; Aortic Valve - diagnostic imaging; Aortic Valve - pathology; Aortic Valve Stenosis - blood; Aortic Valve Stenosis - drug therapy; Aortic Valve Stenosis - mortality; Biological and medical sciences; Biomarkers - blood; Blood Pressure - physiology; calcification; Calcinosis - blood; Calcinosis - mortality; Calcium-Binding Proteins - blood; Calcium-Binding Proteins - metabolism; Cardiology. Vascular system; Cause of Death; Echocardiography; Epidemiology; Extracellular Matrix Proteins - blood; Female; General aspects; Heart; heart failure; Heart Failure - blood; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Male; Matrix Gla Protein; Medical sciences; Middle Aged; Prognosis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Warfarin - therapeutic use; Heart failure; Aortic stenosis; Mortality; Cardiovascular disease; Epidemiology; Medicine; Symptomatology; Association; Cardiac valvular disease; Matrix Gla protein; Cause; all-cause mortality; Calcification
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/j.1365-2796.2010.02264.x

.  Ueland T, Gullestad L, Dahl CP, Aukrust P, Aakhus S, Solberg OG, Vermeer C, Schurgers LJ (Research Institute for Internal Medicine, University of Oslo, Oslo; University of Oslo, Oslo, Norway; and VitaK & Cardiovascular Research Institute CARIM (CV, LS), Maastricht University, Maastricht, The Netherlands) Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med 2010; 268: 483–492. Objective.  Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. Design and subjects.  We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp‐cMGP and dp‐ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. Main outcome measures.  We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp‐ucMGP level in relation to all‐cause mortality in patients with AS. Results.  We found markedly enhanced plasma levels of dp‐cMGP and in particular of dp‐ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp‐ucMGP was associated with cardiac function and long‐term mortality in multivariate analysis. Conclusions.  A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.