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

• Published in: Nutrients Vol. 7; no. 11; pp. 8905 - 8915
• Main Authors: Vossen, Liv, Schurgers, Leon, Van Varik, Bernard, Kietselaer, Bas, Vermeer, Cees, Meeder, Johannes, Rahel, Braim, Van Cauteren, Yvonne, Hoffland, Ge, Rennenberg, Roger, Reesink, Koen, De Leeuw, Peter, Kroon, Abraham
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.10.2015; MDPI
• Subjects: Adult; antagonists; Anticoagulants; Arteries - drug effects; Arteries - metabolism; Arteries - pathology; Atherosclerosis; biomarkers; calcification; Calcium - metabolism; Calcium-Binding Proteins - metabolism; Cardiology; Cardiovascular disease; Clinical Protocols; clinical trials; coronary artery disease; Coronary Artery Disease - drug therapy; Coronary Artery Disease - metabolism; Coronary Artery Disease - pathology; Coronary vessels; Dietary Supplements; Disease Progression; Double-Blind Method; Drug dosages; Extracellular Matrix Proteins - metabolism; Humans; Internal medicine; Matrix Gla Protein; menaquinones; Observational studies; Pathogenesis; patients; placebos; Proteins; Research Design; Tomography; Vascular Calcification - drug therapy; Vein & artery diseases; Vitamin K 2 - analogs & derivatives; Vitamin K 2 - pharmacology; Vitamin K 2 - therapeutic use; Vitamins - pharmacology; Vitamins - therapeutic use; Netherlands; coronary artery calcification; menaquinone-7; matrix gla protein; vascular calcification; vitamin K2
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu7115443

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.