Dataset Information

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

ABSTRACT: 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 ?g/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 ?g/L) and an increasing trend at high dp-uc MGP (?5.31 ?g/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).

SUBMITTER: Wei FF

PROVIDER: S-EPMC6509723 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Wei Fang-Fei FF Thijs Lutgarde L Cauwenberghs Nicholas N Yang Wen-Yi WY Zhang Zhen-Yu ZY Yu Cai-Guo CG Kuznetsova Tatiana T Nawrot Tim S TS Struijker-Boudier Harry A J HAJ Verhamme Peter P Vermeer Cees C Staessen Jan A JA

Journal of the American Heart Association 20190401 7

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 pla ...[more]

PMID: 31025895

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Project description:Background Vascular calcification is strongly related to the risk of mortality and cardiovascular (CV) diseases. In vascular calcification, matrix Gla protein (MGP), a small vitamin K-dependent protein, is an important mineralization inhibitor. Recent studies showed that circulating MGP is associated with mortality risk. However, the longitudinal association between urinary excretion of MGP and all-cause mortality was not established. Materials and methods Urinary MGP was measured in 776 randomly recruited Flemish population (mean age: 51.2 years; 50.9% women) at baseline (during 2005–2010) using capillary electrophoresis coupled with mass spectrometry. Plasma inactive MGP [desphospho-uncarboxylated MGP (dp-ucMGP)] levels were quantified in 646 individuals by ELISA kits. Mortality status was ascertained through the Belgian Population Registry until 2016. The longitudinal association with mortality was determined by the multivariate-adjusted Cox proportional hazards regression models. The multivariate linear regression models were used to identify determinants of urinary MGP level. Results Over the 9.2 years, 47 (6.06%) participants died, including 15 CV deaths. For a doubling of urinary MGP, the hazard ratios (HRs) were 1.31 (95% CI: 1.01–1.69, P = 0.040) for all-cause mortality and 2.05 (95% CI: 1.11–3.79, P = 0.023) for CV mortality with adjustment for covariates, including estimated glomerular filtration rate and urine microalbumin. The addition of urinary MGP to the basic models improved the reclassification as suggested by the increased net reclassification improvement [64.01% (95% CI: 32.64–98.63)] and integrated discrimination improvement [2.33% (95% CI: 0.24–4.71)]. Circulating inactive MGP, total cholesterol, urine microalbumin, and smoking were significantly associated with urinary MGP levels (P ≤ 0.041), independent of sex and age. Conclusion Elevated urinary MGP was associated with an increased risk of all-cause mortality and CV mortality and improved the risk reclassification for all-cause mortality. These findings suggested that urinary MGP might be useful in mortality risk assessment in the general population. However, these observations need to be replicated in larger studies with a longer follow-up time.

Dataset Information

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

Publications

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

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