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

J Intern Med. 2010 Nov;268(5):483-92. doi: 10.1111/j.1365-2796.2010.02264.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use
  • Aorta / diagnostic imaging
  • Aorta / pathology
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / pathology
  • Aortic Valve Stenosis / blood*
  • Aortic Valve Stenosis / drug therapy
  • Aortic Valve Stenosis / mortality*
  • Biomarkers / blood
  • Blood Pressure / physiology
  • Calcinosis / blood
  • Calcinosis / mortality
  • Calcium-Binding Proteins / blood
  • Calcium-Binding Proteins / metabolism*
  • Cause of Death
  • Echocardiography
  • Extracellular Matrix Proteins / blood*
  • Female
  • Heart Failure / blood*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Warfarin