title: 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.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. liv.vossen@mumc.nl.|Department of Internal Medicine, Zuyderland Medical Centre, Sittard 6162BG, The Netherlands. liv.vossen@mumc.nl.
authors.forename: Liv M
authors.initials: LM
authors.lastname: Vossen
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. l.schurgers@maastrichtuniversity.nl.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. b.vanvarik@maastrichtuniversity.nl.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: van Varik
authors.affiliation: Departments of Cardiology and Radiology, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. b.kietselaer@mumc.nl.
authors.forename: Bas L J H
authors.initials: BL
authors.lastname: Kietselaer
authors.affiliation: Group VitaK, Maastricht University, Maastricht 6229EV, The Netherlands. c.vermeer@vitak.com.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. jmeeder@viecuri.nl.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Meeder
authors.affiliation: Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. brahel@viecuri.nl.
authors.forename: Braim M
authors.initials: BM
authors.lastname: Rahel
authors.affiliation: Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. yvonne.cauteren@mumc.nl.
authors.forename: Yvonne J M
authors.initials: YJ
authors.lastname: van Cauteren
authors.affiliation: Department of Radiology, VieCuri Medical Centre, Venlo 5912BL, The Netherlands. ghoffland@viecuri.nl.
authors.forename: Ge A
authors.initials: GA
authors.lastname: Hoffland
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. r.rennenberg@mumc.nl.
authors.forename: Roger J M W
authors.initials: RJ
authors.lastname: Rennenberg
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. k.reesink@maastrichtuniversity.nl.
authors.forename: Koen D
authors.initials: KD
authors.lastname: Reesink
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. p.deleeuw@maastrichtuniversity.nl.|Department of Internal Medicine, Zuyderland Medical Centre, Sittard 6162BG, The Netherlands. p.deleeuw@maastrichtuniversity.nl.|Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. p.deleeuw@maastrichtuniversity.nl.
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. aa.kroon@mumc.nl.|Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. aa.kroon@mumc.nl.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
mesh_terms: D000328:Adult; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002985:Clinical Protocols; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D012107:Research Design; D061205:Vascular Calcification / Q000188:drug therapy*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use*; D000097568:Matrix Gla Protein
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D024482:Vitamin K 2; D014815:Vitamins; D000097568:Matrix Gla Protein; C062629:menaquinone 7
keywords: coronary artery calcification; matrix gla protein; menaquinone-7; vascular calcification; vitamin K2