Knapen Marjo H J, Braam Lavienja A J L M, Drummen Nadja E, Bekers Otto, Hoeks Arnold P G, Vermeer Cees
Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht, Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax: +31 43 388 5889, E-mail:
Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19.
Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.
观察性数据表明,甲萘醌(MK,维生素K2)摄入量与心血管(CV)健康之间存在联系。然而,缺乏以血管终点为指标的MK干预试验。我们在一项双盲、安慰剂对照试验中研究了补充MK-7(180微克menaQ7/天)对动脉僵硬度的长期影响。健康的绝经后女性(n = 244)接受安慰剂(n = 124)或MK-7(n = 120)治疗三年。通过回声跟踪测量局部颈动脉僵硬度指标(内膜中层厚度IMT、舒张末期直径和扩张度)。使用机械换能器测量区域主动脉僵硬度(分别为颈动脉-股动脉和颈动脉-桡动脉脉搏波速度,cfPWV和crPWV)。测量循环中的去磷酸化未羧化基质Gla蛋白(dp-ucMGP)以及急性期标志物白细胞介素-6(IL-6)、高敏C反应蛋白(hsCRP)、肿瘤坏死因子-α(TNF-α)和内皮功能障碍标志物血管细胞粘附分子(VCAM)、E-选择素和晚期糖基化终产物(AGEs)。在基线时,dp-ucMGP与IMT、直径、cfPWV以及急性期标志物(APMscore)和内皮功能障碍标志物(EDFscore)的平均z评分相关。补充MK-7三年后,整个组的cfPWV和僵硬度指数β显著降低,而基线僵硬度指数β高于中位数10.8的女性的扩张度、顺应性、扩张性、杨氏模量和局部颈动脉脉搏波速度(cPWV)有所改善。与安慰剂相比,MK-7使dp-ucMGP降低了50%,但对急性期和内皮功能障碍标志物没有影响。总之,长期使用MK-7补充剂可改善健康绝经后女性的动脉僵硬度,尤其是动脉僵硬度较高的女性。