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

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.

• Authors: 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
• Journal: Nutrients (Nutrients) Vol. 7 Issue 11 Pg. 8905-15 (Oct 28 2015) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 26516910 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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