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

Author:

Diederichsen Axel C.P.1ORCID,Lindholt Jes S.2ORCID,Möller Sören3,Øvrehus Kristian A.1,Auscher Søren4,Lambrechtsen Jess4,Hosbond Susanne E.5,Alan Dilek H.5,Urbonaviciene Grazina6,Becker Søren W.6,Fredgart Maise H.1ORCID,Hasific Selma1ORCID,Folkestad Lars7,Gerke Oke8ORCID,Rasmussen Lars Melholt9ORCID,Møller Jacob E.10,Mickley Hans1,Dahl Jordi S.1

Affiliation:

1. Department of Cardiology (A.C.P.D., K.A.Ø., M.H.F., S.H.‚ H.M., J.S.D.), Odense University Hospital, Denmark.

2. Department of Cardiothoracic and Vascular Surgery (J.S.L.), Odense University Hospital, Denmark.

3. Open Patient Data Explorative Network (S.M.), Odense University Hospital, Denmark.

4. Department of Cardiology, Svendborg Hospital, Denmark (S.A., J.L.).

5. Department of Cardiology, Lillebaelt Hospital, Vejle, Denmark (S.E.H.‚ D.H.A.).

6. Department of Cardiology, Regional Hospital Central Jutland, Silkeborg, Denmark (G.U., S.W.B.).

7. Department of Endocrinology (L.F.), Odense University Hospital, Denmark.

8. Department of Nuclear Medicine (O.G.), Odense University Hospital, Denmark.

9. Department of Clinical Biochemistry and Pharmacology (L.M.R.), Odense University Hospital, Denmark.

10. Department of Cardiology, Copenhagen University Hospital, Denmark (J.E.M.).

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 cm 2 (95% CI, –0.09 to 0.12 cm 2 ; 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. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03243890.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Cited by 33 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3