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.
Highlights
Introduction and RationaleCoronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis [1] and is a strong and independent risk marker of cardiovascular complications [2,3]
We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC in comparison to placebo and that MK-7 supplementation may lead to a treatment option for vascular calcification and cardiovascular disease
Eligible patients suspected of having coronary artery disease (CAD) and who are scanned by 128-slice multiple detector Computed Tomography (CT) (MDCT) to assess the presence of coronary atherosclerotic plaques and CAC will be identified from the outpatient clinic of the departments of Cardiology
Summary
Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis [1] and is a strong and independent risk marker of cardiovascular complications [2,3]. Inhibition of the vitamin-K-cycle by vitamin K antagonists (VKA) results in the accumulation of uncarboxylated MGP which is biologically inactive This is associated with extensive arterial calcification in experimental animals [5,8]. Phylloquinone supplementation itself was shown to slow the progression of CAC and had a beneficial effect on vascular stiffness in healthy adults with coronary artery calcification after 3 years of follow-up [19,20,21]. First it will be the first RCT to study the effect of nutritional supplementation with MK-7 on the progression of arterial calcification using state of the art techniques for the quantification of calcification in atherosclerotic lesions in patients with pre-existing CAC. For example the MK-7 content of Japanese fermented food natto is approximately 1000 μg/100 g in a highly bioactive form for gamma-carboxylation of hepatic and extrahepatic Gla proteins [12,25]
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