Dataset Information

Renal Resistive Index Is Associated With Inactive Matrix Gla (?-Carboxyglutamate) Protein in an Adult Population-Based Study.

ABSTRACT: Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (?-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (<38 years; P=0.62), whereas it was significant in older age groups (38-55 and >55 years; P=0.016 and P<0.001, respectively). Conclusions Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.

SUBMITTER: Jaques DA

PROVIDER: S-EPMC6818003 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study.

Jaques David A DA Pivin Edward E Pruijm Menno M Ackermann Daniel D Guessous Idris I Ehret Georg G Wei Fang-Fei FF Staessen Jan A JA Pechère-Bertschi Antoinette A Vermeer Cees C Vogt Bruno B Burnier Michel M Martin Pierre-Yves PY Bochud Murielle M Ponte Belen B

Journal of the American Heart Association 20190912 18

Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results W ...[more]

PMID: 31510823

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Project description: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).

Dataset Information

Renal Resistive Index Is Associated With Inactive Matrix Gla (?-Carboxyglutamate) Protein in an Adult Population-Based Study.

Publications

Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study.

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