Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in African American Hemodialysis Patients

• Published in: American journal of hypertension 2018-05, Vol.31 (6), p.735-741
• Main Authors: Fain, Mary Ellen, Kapuku, Gaston K, Paulson, William D, Williams, Celestine F, Raed, Anas, Dong, Yanbin, Knapen, Marjo H J, Vermeer, Cees, Pollock, Norman K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - blood; Black or African American; Calcium-Binding Proteins - blood; Cardiovascular Diseases - blood; Cardiovascular Diseases - ethnology; Cardiovascular Diseases - physiopathology; Case-Control Studies; Cross-Sectional Studies; Endothelium, Vascular - physiopathology; Extracellular Matrix Proteins - blood; Female; Humans; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - ethnology; Kidney Failure, Chronic - physiopathology; Kidney Failure, Chronic - therapy; Male; Matrix Gla Protein; Middle Aged; Renal Dialysis; Risk Factors; Up-Regulation; Vascular Stiffness; Young Adult
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1093/ajh/hpy049

Abstract BACKGROUND Matrix Gla protein (MGP) is a vascular calcification inhibitor dependent upon vitamin K for activation. Evidence suggests that elevated plasma inactive MGP levels (desphospho-uncarboxylated MGP, dp-ucMGP; indicating poorer vascular vitamin K status) are associated with greater cardiovascular disease (CVD) risk. Despite African Americans experiencing highest rates of kidney failure and CVD events, relationships between dp-ucMGP and CVD risk markers have not been examined in this population. We investigated vascular vitamin K status (via plasma dp-ucMGP) between African American hemodialysis (HD) patients and healthy controls, and the associations of dp-ucMGP with arterial stiffness and endothelial function in HD patients only. METHODS In 37 African American HD patients and 37 age- and race-matched controls, plasma dp-ucMGP was measured by enzyme immunoassay as a marker of vascular vitamin K status. Carotid-femoral pulse wave velocity (PWV; arterial stiffness measurement) and brachial artery flow-mediated dilation (FMD; endothelial function measurement) were assessed by applanation tonometry and ultrasound, respectively, in HD patients only. RESULTS Mean dp-ucMGP levels were 5.6 times higher in HD patients vs. controls (2,139 ± 1,102 vs. 382 ± 181 pmol/l, P < 0.01). Multiple linear regression, adjusting for age, sex, dialysis vintage, diabetes mellitus, CVD history, body mass index, and blood pressure, revealed that dp-ucMGP was independently related to PWV (standardized β = 0.49) and FMD (standardized β = −0.53) (both P < 0.01). CONCLUSIONS Our data suggest that the higher plasma dp-ucMGP concentrations found in African American HD patients may be associated with greater arterial stiffness and endothelial dysfunction.