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


METHODS
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.


METHODS
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.
Ueland
T
T
Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. thor.ueland@medisin.uio.no
Gullestad
L
L
Dahl
C P
CP
Aukrust
P
P
Aakhus
S
S
Solberg
O G
OG
Vermeer
C
C
Schurgers
L J
LJ
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D002114:Calcinosis / Q000097:blood / Q000401:mortality; D002135:Calcium-Binding Proteins / Q000097:blood / Q000378:metabolism*; D002423:Cause of Death; D004452:Echocardiography; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014859:Warfarin / Q000627:therapeutic use; D000097568:Matrix Gla Protein
D000925:Anticoagulants; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014859:Warfarin; D000097568:Matrix Gla Protein