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

Am J Hypertens. 2018 May 7;31(6):735-741. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins