维生素 K2 和 D 在主动脉瓣钙化患者中的应用：一项随机、双盲临床试验。
Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.
机构信息
Department of Cardiology (A.C.P.D., K.A.Ø., M.H.F., S.H.' H.M., J.S.D.), Odense University Hospital, Denmark.
Department of Cardiothoracic and Vascular Surgery (J.S.L.), Odense University Hospital, Denmark.
出版信息
Circulation. 2022 May 3;145(18):1387-1397. doi: 10.1161/CIRCULATIONAHA.121.057008. Epub 2022 Apr 25.
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; =0.64). The mean change in aortic valve area was 0.02 cm (95% CI, -0.09 to 0.12 cm; =0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; =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; =0.99), all-cause death (1 versus 4 patients; =0.37), or cardiovascular events (10 versus 10 patients; =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; <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.
背景
甲萘醌-7（MK-7），也称为维生素 K2，是参与抑制动脉钙化的蛋白质羧化的辅助因子，并且已被证明可降低主动脉瓣狭窄患者主动脉瓣钙化（AVC）的进展速度。
方法
在一项随机、双盲、多中心试验中，社区中的男性通过心脏非对比计算机断层扫描获得 AVC 评分>300 个单位（AU），随机分为每日服用 720µg MK-7 加 25µg 维生素 D 或匹配的安慰剂，治疗 24 个月。主要结局是 AVC 评分的变化。选定的次要结局包括经超声心动图测量的主动脉瓣面积和峰值主动脉射流速度、心脏瓣膜手术、主动脉和冠状动脉钙化的变化以及 dp-ucMGP（去磷酸化未羧化基质 Gla 蛋白）的变化。安全性结局包括全因死亡和心血管事件。
结果
从 2018 年 2 月 1 日至 2019 年 3 月 21 日，365 名男性被随机分组。平均年龄为 71.0（±4.4）岁。干预组和安慰剂组的 AVC 评分分别平均增加 275 AU（95%CI，225-326 AU）和 292 AU（95%CI，246-338 AU）。进展差异的平均值为 17 AU（95%CI，-86 至 53 AU；=0.64）。主动脉瓣面积的平均变化为 0.02cm（95%CI，-0.09 至 0.12cm；=0.78），峰值主动脉射流速度的平均变化为 0.04m/s（95%CI，-0.11 至 0.02m/s；=0.21）。MK-7 加维生素 D 治疗组和安慰剂组患者的主动脉和冠状动脉钙化评分进展无显著差异。心脏瓣膜手术（1 例与 2 例患者；=0.99）、全因死亡（1 例与 4 例患者；=0.37）或心血管事件（10 例与 10 例患者；=0.99）的发生率无差异。与安慰剂组相比，MK-7 加维生素 D 治疗可显著降低 dp-ucMGP（-212 pmol/L 与 45 pmol/L；<0.001）。
结论
在 AVC 评分>300 AU 的老年男性中，2 年的 MK-7 加维生素 D 补充并未影响 AVC 的进展。
登记
网址：https://www.
临床试验
gov；独特标识符：NCT03243890。
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