Prevalence and effects of functional vitamin K insufficiency: The PREVEND study

Ineke J. Riphagen, Charlotte A. Keyzer, Nadja E.A. Drummen, Martin H. de Borst, Joline W.J. Beulens, Ron T. Gansevoort, Johanna M. Geleijnse, Frits A.J. Muskiet, Gerjan Navis, Sipke T. Visser, Cees Vermeer, Ido P. Kema, Stephan J.L. Bakker

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Matrix Gla Protein (MGP) is a strong vitamin K-dependent inhibitor of soft tissue calcification. We assessed the prevalence of functional vitamin K insufficiency, as derived from plasma desphospho-uncarboxylated MGP (dp-ucMGP), and investigated whether plasma dp-ucMGP is associated with all-cause and cardiovascular mortality in a large general population-based cohort. We included 4275 subjects (aged 53 ± 12 years, 46.0% male) participating in the prospective general population-based Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. The prevalence of functional vitamin K insufficiency (i.e., dp-ucMGP > 500 pmol/L) was 31% in the total study population. This prevalence was significantly higher among elderly and subjects with comorbidities like hypertension, type 2 diabetes, chronic kidney disease, and cardiovascular disease (~50%). After 10 years of follow-up, 279 subjects had died, with 74 deaths attributable to cardiovascular causes. We found significant J-shaped associations of plasma dp-ucMGP with all-cause (linear term: hazard ratio (HR) (95% confidence interval (CI)) = 0.20 (0.12–0.33), p < 0.001; squared term: 1.14 (1.10–1.17), p < 0.001) and cardiovascular mortality (linear term: 0.12 (0.05–0.27), p < 0.001; squared term: 1.17 (1.11–1.23), p < 0.001). These associations remained significant after adjustment for potential confounders. Whether the correction of vitamin K insufficiency improves health outcomes needs to be addressed in future prospective intervention studies.

Original languageEnglish
Article number1334
Issue number12
Publication statusPublished - 8 Dec 2017


  • All-cause mortality
  • Cardiovascular mortality
  • Matrix Gla protein
  • Vitamin K

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