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

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

Author information

1
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. liv.vossen@mumc.nl.
2
Department of Internal Medicine, Zuyderland Medical Centre, Sittard 6162BG, The Netherlands. liv.vossen@mumc.nl.
3
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. l.schurgers@maastrichtuniversity.nl.
4
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. b.vanvarik@maastrichtuniversity.nl.
5
Departments of Cardiology and Radiology, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. b.kietselaer@mumc.nl.
6
Group VitaK, Maastricht University, Maastricht 6229EV, The Netherlands. c.vermeer@vitak.com.
7
Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. jmeeder@viecuri.nl.
8
Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. brahel@viecuri.nl.
9
Department of Cardiology, VieCuri Medical Centre, Venlo 5912 BL, The Netherlands. yvonne.cauteren@mumc.nl.
10
Department of Radiology, VieCuri Medical Centre, Venlo 5912BL, The Netherlands. ghoffland@viecuri.nl.
11
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. r.rennenberg@mumc.nl.
12
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. k.reesink@maastrichtuniversity.nl.
13
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. p.deleeuw@maastrichtuniversity.nl.
14
Department of Internal Medicine, Zuyderland Medical Centre, Sittard 6162BG, The Netherlands. p.deleeuw@maastrichtuniversity.nl.
15
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. p.deleeuw@maastrichtuniversity.nl.
16
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. aa.kroon@mumc.nl.
17
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht 6229ER, The Netherlands. aa.kroon@mumc.nl.

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

PMID:
26516910
PMCID:
PMC4663571
DOI:
10.3390/nu7115443
[Indexed for MEDLINE]
Free PMC Article

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