TY - JOUR
T1 - Central Hemodynamics in Relation to Circulating Desphospho-Uncarboxylated Matrix Gla Protein
T2 - A Population Study
AU - Wei, Fang-Fei
AU - Thijs, Lutgarde
AU - Cauwenberghs, Nicholas
AU - Yang, Wen-Yi
AU - Zhang, Zhen-Yu
AU - Yu, Cai-Guo
AU - Kuznetsova, Tatiana
AU - Nawrot, Tim S.
AU - Struijker-Boudier, Harry A. J.
AU - Verhamme, Peter
AU - Vermeer, Cees
AU - Staessen, Jan A.
N1 - Funding Information:
This work was supported by the European Union (HEALTH-F7-305507-HOMAGE), the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET), and the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT); and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and 11Z0916N), supported the Studies Coordinating Center in Leuven, Belgium.
Publisher Copyright:
© 2019 The Authors.
PY - 2019/4/2
Y1 - 2019/4/2
N2 - 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-ucMGP).Methods and Results-In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-ucMGP, 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-ucMGP was 4.09 mu g/L. All hemodynamic indexes increased across tertiles of dp-ucMGP distribution. In multivariable-adjusted analyses, a doubling of dp-ucMGP 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-ucMGP (= 5.31 mu g/L).Conclusions-In people representative for the general population, higher inactive dp-ucMGP 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).
AB - 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-ucMGP).Methods and Results-In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp-ucMGP, 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-ucMGP was 4.09 mu g/L. All hemodynamic indexes increased across tertiles of dp-ucMGP distribution. In multivariable-adjusted analyses, a doubling of dp-ucMGP 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-ucMGP (= 5.31 mu g/L).Conclusions-In people representative for the general population, higher inactive dp-ucMGP 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).
KW - AORTIC STIFFNESS
KW - ARTERIAL STIFFNESS
KW - CALCIFICATION
KW - HEART-FAILURE
KW - MENAQUINONE-7 SUPPLEMENTATION
KW - PRESSURE
KW - PULSE-WAVE VELOCITY
KW - REFLECTION
KW - VITAMIN-K
KW - WOMEN
KW - aortic stiffness
KW - calcification
KW - hemodynamics
KW - matrix proteins
KW - pulse pressure
U2 - 10.1161/JAHA.119.011960
DO - 10.1161/JAHA.119.011960
M3 - Article
C2 - 31025895
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 7
M1 - 011960
ER -