Department of Pharmacology, Clinical Pharmacology and Therapy, Varna Medical University, Varna, Bulgaria.
First Department of Internal Diseases, Faculty of Medicine, Medical University of Varna, Varna, Bulgaria.
Kaohsiung J Med Sci. 2021 Jul;37(7):624-631. doi: 10.1002/kjm2.12373. Epub 2021 Feb 26.
The present cross-sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K-dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non-users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla-protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla-rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non-users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non-users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non-users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.
本横断面临床研究旨在探讨心血管疾病（CVD）患者中他汀类药物暴露、冠状动脉钙化（CAC）和维生素 K 依赖性蛋白（VKDPs）之间的关系。研究了两组患者：患有明确 CVD 的患者（CVD 组）和 CVD 中度风险的健康患者（对照组）。这两组患者也分为他汀类药物使用者和非使用者。测量了血浆中的以下 VKDPs：未羧化基质 Gla 蛋白（ucMGP）、未羧化（ucOC）和羧化骨钙素（cOC）、Gla 富含蛋白（GRP）。通过多层计算机断层扫描确定 CAC 评分（CACS）。在研究的所有参与者中，与非使用者相比，他汀类药物使用者的 CACS 更为明显；在 CVD 患者和对照组中也发现了同样的情况。虽然 ucMGP 和 GRP 的水平在他汀类药物使用者和非使用者之间没有差异，但 ucOC 和 ucOC/cOC 在他汀类药物使用者中显著升高，表明存在维生素 K 缺乏。在整个人群和他汀类药物使用者组中，ucOC 水平与 CACS 之间呈正相关，但在他汀类药物非使用者中则无相关性。ucMGP 或 GRP 与 CACS 之间无相关性。他汀类药物还对国际标准化比值有影响，并与维生素 K 拮抗剂（VKAs）相互作用。我们的研究结果与他汀类药物与血管钙化之间存在正相关的现有证据一致。它们在一定程度上阐明了他汀类药物可能通过抑制维生素 K 依赖性蛋白和参与血管保护的功能来增强动脉壁钙积累的可能机制。
