Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
CIRO, Center of Expertise for Chronic Organ Failure, Horn, The Netherlands.
Respir Res. 2017 Nov 13;18(1):189. doi: 10.1186/s12931-017-0673-z.
Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.
心血管疾病在慢性阻塞性肺疾病（COPD）患者中很常见。它们的共存意味着许多 COPD 患者需要抗凝治疗。虽然越来越多的直接口服抗凝剂（DOACs）取代了维生素 K 拮抗剂（VKAs），但 VKAs 仍被广泛使用。VKAs 会导致维生素 K 严重缺乏，而维生素 K 是凝血途径中一种关键的激活剂。然而，人们已经认识到，维生素 K 也是其他细胞外蛋白质（如基质 Gla 蛋白（MGP））激活的必需辅助因子，MGP 是动脉钙化的一种强有力抑制剂。由于使用 VKAs 导致 MGP 激活不足或缺乏，会导致血管钙化迅速进展，这可能会增加明显心血管疾病的风险。另一方面，维生素 K 的摄入似乎对动脉的矿化有保护作用。此外，血管钙化与弹性蛋白降解相互关联，在 COPD 患者中，弹性蛋白降解加速，与生存能力受损有关。在这篇评论中，我们假设维生素 K 是弹性蛋白降解速度的关键决定因素。我们推测 VKAs 状态不佳与 COPD 发病机制的关键机制之间可能存在联系，并对该疾病患者使用 VKAs 提出担忧。需要进一步的干预研究来探索维生素 K 补充是否能够减少 COPD 患者的弹性蛋白降解和血管钙化。
