Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial

Abstract

Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 μg MK-7 plus 25 μg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.

Long-Duration Space Travel Support Must Consider Wider Influences to Conserve Microbiota Composition and Function

“…While vitamin K1 (phylloquinone) is plant derived, vitamin K2 (menaquinone) is produced by the gut microbiota. This K2 improves bone mineral density [ 61 ], but supplementation through oral intake of both K2 and D in the elderly has been shown to be ineffective at ameliorating aortic valve calcification [ 62 ]. This may also be the case in astronauts who have been in space for 6 months or more who develop arterial stiffness during flight [ 63 ], while other astronauts present improvements in bone metabolism markers upon vitamin K supplementation [ 50 ].…”

Therapie der Aortenklappenstenose jenseits des Klappenersatzes – Was bringt die Zukunft?

“…Erst kürzlich wurden die Ergebnisse der AVADEC-Studie veröffentlicht, in welcher der Effekt einer Vitamin-K 2 -und Vitamin-D-Supplementation auf Männer mit Aortenklappenstenose untersucht wurde. Es ließ sich kein Unterschied durch die Behandlung auf den Progress des Kalzium-Scores in der CT oder der hämodynamischen Parameter über 2 Jahre feststellen [18].…”

“…Die SALTIRE-II-Studie untersuchte den Effekt von Denosumab oder dem Bisphosphonat Alendronat bei 150 Patienten mit leichtbis mittelgradiger AKS. Nach einer Beobachtungsdauer von 2 Jahren ergab sich kein Unterschied im Stenoseprogress zwischen den Gruppen, gemessen mittels Echokardiografie, CT und 18 F-NaF-Positronenemissionstomografie-CT [19].…”

Letter by Omarjee Regarding Article, “Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial”

“…Diederichsen et al reported that supplementation with vitamin K2 MK-7 plus vitamin D was ineffective in reducing the progression of aortic valve calcification (AVC) and aortic stenosis in men after 2 years of therapy. 1 This negative result raises several questions.…”

“…1 Patients were stratified according to AVC score (300–599 AU or ≥600 AU). 1 Dweck et al showed that AVC stages corresponded to AVC scores (aortic sclerosis: 343±377 AU; aortic stenosis: mild: 702±485 AU, moderate 2084±1324 AU, and severe 3956±2300 AU). 2 A primary end point for these stages would be more relevant.…”