Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial)

Liv M. Vossen*, Leon J. Schurgers, Bernard J. van Varik, Bas L. J. H. Kietselaer, Cees Vermeer, Johannes G. Meeder, Braim M. Rahel, Yvonne J. M. van Cauteren, Ge A. Hoffland, Roger J. M. W. Rennenberg, Koen D. Reesink, Peter W. de Leeuw, Abraham A. Kroon

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
Original languageEnglish
Pages (from-to)8905-8915
Issue number11
Publication statusPublished - Nov 2015


  • vascular calcification
  • coronary artery calcification
  • matrix gla protein
  • vitamin K2
  • menaquinone-7

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