Central Hemodynamics in Relation to Circulating Desphospho-Uncarboxylated Matrix Gla Protein: A Population Study

J Am Heart Assoc. 2019 Apr 2;8(7):e011960. doi: 10.1161/JAHA.119.011960.


Background Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho-uncarboxylated MGP (dp-uc MGP ). Methods and Results In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-uc MGP , using an ELISA -based assay. We derived central pulse pressure and carotid-femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure-based wave separation analysis algorithm. Aortic PWV (n=657), central pulse pressure, forward pulse wave, and backward pulse wave mean± SD values were 7.34±1.64 m/s, 45.2±15.3 mm Hg, 33.2±10.2 mm Hg, and 21.8±8.6 mm Hg, respectively. The geometric mean plasma concentration of dp-uc MGP was 4.09 μg/L. All hemodynamic indexes increased across tertiles of dp-uc MGP distribution. In multivariable-adjusted analyses, a doubling of dp-uc MGP was associated with higher PWV (0.15 m/s; 95% CI, 0.01-0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49-2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01-1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11-1.30 mm Hg). Categorization of aortic PWV by tertiles of its distribution highlighted a decreasing trend of PWV at low dp-uc MGP (<3.35 μg/L) and an increasing trend at high dp-uc MGP (≥5.31 μg/L). Conclusions In people representative for the general population, higher inactive dp-uc MGP was associated with greater PWV , central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status).

Keywords: aortic stiffness; calcification; hemodynamics; matrix proteins; pulse pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Belgium
  • Blood Pressure*
  • Calcium-Binding Proteins / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Hemodynamics / physiology*
  • Humans
  • Male
  • Manometry
  • Middle Aged
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Pulse Wave Analysis*
  • Vascular Calcification
  • Vascular Stiffness
  • Vitamin K / metabolism


  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Vitamin K