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Inactive Matrix Gla Protein is Associated with Arterial Stiffness and Vascular Endothelial Function in African‐American Hemodialysis Patients
Author(s) -
Fain Mary Ellen,
Nguyen Joshua,
Kapuku Gaston K,
Paulson William D,
White John J,
Dong Yanbin,
Pollock Norman K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.293.8
Subject(s) - medicine , arterial stiffness , matrix gla protein , hemodialysis , cardiology , brachial artery , pulse wave velocity , end stage renal disease , population , renal function , kidney disease , blood pressure , hyperphosphatemia , environmental health
Pulse wave velocity (PWV), a marker of aortic stiffness, and brachial artery flow‐mediated dilation (FMD), a measure of endothelial dysfunction, are both independent predictors of future cardiovascular disease (CVD) events and mortality. Given that end‐stage renal disease patients receiving hemodialysis are at marked increased risk for CVD combined with recent data suggesting that African Americans (AA) are three times more likely to experience kidney failure, it is vital to identify modifiable CVD related factors that could represent therapeutic targets in this population. Matrix Gla protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated, and recent evidence suggest that higher circulating levels of inactive MGP, known as dephospho‐uncarboxylated MGP (dp‐ucMGP), are linked to CVD events and mortality. Currently, the relationship between inactive MGP and markers of arterial stiffness and endothelial function has not been investigated in AA hemodialysis patients. This study was conducted 1) to compare plasma levels of dp‐ucMGP between AA hemodialysis patients and age‐ and race‐matched controls; and 2) to determine associations of dp‐ucMGP with PWV and FMD in the cohort of AA hemodialysis patients. Fasting plasma dp‐ucMGP concentrations, carotid‐femoral PWV by applanation tonometry, and brachial artery FMD by ultrasound were measured in 37 AA hemodialysis patients (mean age: 47.7 ± 10.4 years). Thirty‐seven AA adults without renal disease (mean age: 47.7 ± 7.4) served as controls for plasma dp‐ucMGP levels. Plasma dp‐ucMGP levels were significantly higher in hemodialysis patients compared to controls (2129 ± 1117 vs. 382 ± 181 pmol/L, P < 0.01). In analyses with multivariate linear regression adjusting for age, sex, body mass index, and mean arterial pressure, PWV ( β = 0.42) and FMD ( β = −0.52) were associated with dp‐ucMGP (both P < 0.01). These data suggest that higher levels of dp‐ucMGP found in AA hemodialysis patients may be associated with increased arterial stiffness and endothelial dysfunction. Experimental trials are needed to determine whether vitamin K supplementation slows arterial stiffening and endothelial dysfunction by increasing MGP carboxylation. Support or Funding Information Georgia Regents University's Intramural Grant Program