1 Studies Coordinating Centre Research Unit Hypertension and Cardiovascular Epidemiology Department of Cardiovascular Sciences University of Leuven Belgium.
2 Centre for Environmental Sciences Hasselt University Diepenbeek Belgium.
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).
大动脉僵硬度和钙化是心血管并发症的先兆。MGP(基质 Gla 蛋白)需要维生素 K 依赖性激活,是一种有效的局部动脉钙化抑制剂。我们假设中心血流动力学特性可能与无活性去羧基未羧化 MGP(dp-uc MGP)有关。
在 835 名随机招募的佛兰芒个体(平均年龄 49.7 岁;45.6%为女性)中,我们使用基于 ELISA 的测定法测量了血浆 dp-uc MGP。我们从平板测压法中得出中心脉压和颈股脉搏波速度(PWV),并使用自动压力分离波分析算法计算前向和后向脉搏波。主动脉 PWV(n=657)、中心脉压、前向脉搏波和后向脉搏波的平均值±SD 值分别为 7.34±1.64m/s、45.2±15.3mmHg、33.2±10.2mmHg 和 21.8±8.6mmHg。dp-uc MGP 的几何平均血浆浓度为 4.09μg/L。所有血流动力学指标均随 dp-uc MGP 分布三分位的增加而增加。在多变量调整分析中,dp-uc MGP 加倍与更高的 PWV(0.15m/s;95%CI,0.01-0.28 m/s)、中心脉压(1.70mmHg;95%CI,0.49-2.91mmHg)、前向脉搏波(0.93mmHg;95%CI,0.01-1.84mmHg)和后向脉搏波(0.71mmHg;95%CI,0.11-1.30mmHg)相关。根据主动脉 PWV 分布的三分位数进行分类,提示在低 dp-uc MGP(<3.35μg/L)时 PWV 呈下降趋势,在高 dp-uc MGP(≥5.31μg/L)时呈上升趋势。
在具有代表性的一般人群中,较高的无活性 dp-uc MGP 与更高的 PWV、中心脉压、前向脉搏波和后向脉搏波相关。这些观察结果突出了保持血管完整性和预防心血管并发症的新途径(例如,通过改善人的维生素 K 状态)。