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

Nutrients. 2015 Oct 28;7(11):8905-15. doi: 10.3390/nu7115443.

Abstract

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.

Keywords: coronary artery calcification; matrix gla protein; menaquinone-7; vascular calcification; vitamin K2.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arteries / drug effects*
  • Arteries / metabolism
  • Arteries / pathology
  • Calcium / metabolism*
  • Calcium-Binding Proteins / metabolism
  • Clinical Protocols
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Dietary Supplements*
  • Disease Progression
  • Double-Blind Method
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Research Design
  • Vascular Calcification / drug therapy*
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / pharmacology
  • Vitamin K 2 / therapeutic use
  • Vitamins / pharmacology
  • Vitamins / therapeutic use*

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Vitamins
  • matrix Gla protein
  • Vitamin K 2
  • vitamin MK 7
  • Calcium