Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease

Maturitas. 2014 Feb;77(2):137-41. doi: 10.1016/j.maturitas.2013.10.008. Epub 2013 Oct 24.


Objectives: Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals.

Study design: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data.

Main outcome measures: Incidence of CVD.

Results: After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD.

Conclusions: Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.

Keywords: CVD; Cardiovascular disease; Gla; LASA; Longitudinal Aging Study Amsterdam; MGP; Matrix Gla-protein; Vitamin K status; cardiovascular events and disease; desphospho-carboxylated MGP; desphospho-uncarboxylated MGP; dp-cMGP; dp-ucMGP; matrix Gla protein; γ-carboxyglutamate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Matrix Gla Protein
  • Middle Aged
  • Netherlands / epidemiology
  • Risk Factors
  • Vitamin K Deficiency / blood*
  • Vitamin K Deficiency / complications


  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins