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

Vossen LM, Schurgers LJ, van Varik BJ, Kietselaer BL, Vermeer C, Meeder JG, Rahel BM, van Cauteren YJ, Hoffland GA, Rennenberg RJ, Reesink KD, de Leeuw PW, Kroon AA - Nutrients (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. liv.vossen@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.

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nutrients-07-05443-f001: Trial design.

Mentions: Treatment of both groups will last for 24 months. During this time participants will visit our research unit five times, at 6-month intervals (Figure 1). At every study visit we will perform an interview and blood pressure measurements. During the first visit, at 12, and at 24 months of follow-up, measurements of CABP, cfPWV, crPWV, cIMT and DC are scheduled. In addition, fasting blood-samples will be drawn at 0, 12, and 24 months. We will repeat CT-scans of the heart and coronary arteries at 12 and 24 months of follow-up. At 12 months only a non-contrast CT scan will be performed to obtain a calcium score. At 24 months a CT-angiography will be performed, using the same acquisition protocol and reconstruction techniques as the initial CT scan (See Figure 1).


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

Vossen LM, Schurgers LJ, van Varik BJ, Kietselaer BL, Vermeer C, Meeder JG, Rahel BM, van Cauteren YJ, Hoffland GA, Rennenberg RJ, Reesink KD, de Leeuw PW, Kroon AA - Nutrients (2015)

Trial design.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663571&req=5

nutrients-07-05443-f001: Trial design.
Mentions: Treatment of both groups will last for 24 months. During this time participants will visit our research unit five times, at 6-month intervals (Figure 1). At every study visit we will perform an interview and blood pressure measurements. During the first visit, at 12, and at 24 months of follow-up, measurements of CABP, cfPWV, crPWV, cIMT and DC are scheduled. In addition, fasting blood-samples will be drawn at 0, 12, and 24 months. We will repeat CT-scans of the heart and coronary arteries at 12 and 24 months of follow-up. At 12 months only a non-contrast CT scan will be performed to obtain a calcium score. At 24 months a CT-angiography will be performed, using the same acquisition protocol and reconstruction techniques as the initial CT scan (See Figure 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. liv.vossen@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.

Show MeSH
Related in: MedlinePlus