Zhang Allan Jean, Ballantyne Christie M, Birnbaum Yochai
School of Medicine, Baylor College of Medicine, Houston, TX, USA.
The Section of Cardiology, The Department of Medicine, Baylor College of Medicine, 7200 Cambridge Street, MS BCM620, Houston, TX, 77030, USA.
Cardiovasc Drugs Ther. 2024 Dec 13. doi: 10.1007/s10557-024-07661-2.
Several reports suggest that in animal models, as well as in the clinical setting, long-term warfarin use increases coronary artery calcifications. The same has been reported for statins prescribed for patients at risk or with established atherosclerosis. Coronary calcifications are considered a risk marker for further cardiovascular events. However, numerous clinical trials have established that statins reduce the risk for cardiovascular events. Warfarin also has been shown to reduce the risk of cardiovascular events, including re-infarction. It has been suggested that the increase in coronary calcification can be viewed as a marker of stabilization of the coronary plaque in such patients. Warfarin inhibits the activation of Vitamin K epoxide reductase complex 1 (VKORC1), which blocks the regeneration of reduced vitamin K1 and K2. Vitamin K1 is predominantly localized to the liver, serving to carboxylate clotting factors. Vitamin K2 travels through systemic circulation, with significant and wide-ranging effects. Several studies using animal models of atherosclerosis have shown that vitamin K2 supplement can attenuate the progression of atherosclerosis, as well as coronary calcification. Clinical studies supporting this effect in patients are lacking. Yet, there is an increase in the use of over-the-counter vitamin K2 supplements, and several manuscripts recommended its use in patients receiving long-term warfarin to attenuate coronary calcification. However, it is unclear if this occurs in patients with atherosclerosis receiving warfarin or statins and if attenuating coronary calcification has beneficial or detrimental effects on cardiovascular outcomes.
多项报告表明，在动物模型以及临床环境中，长期使用华法林会增加冠状动脉钙化。对于有风险或已患有动脉粥样硬化的患者所开的他汀类药物，也有同样的报告。冠状动脉钙化被认为是进一步发生心血管事件的风险标志物。然而，众多临床试验已证实他汀类药物可降低心血管事件的风险。华法林也已被证明可降低心血管事件的风险，包括再梗死。有人提出，冠状动脉钙化的增加可被视为此类患者冠状动脉斑块稳定的一个标志物。华法林抑制维生素K环氧还原酶复合体1（VKORC1）的激活，这会阻断还原型维生素K1和K2的再生。维生素K1主要定位于肝脏，用于使凝血因子羧化。维生素K2通过体循环，具有显著且广泛的作用。几项使用动脉粥样硬化动物模型的研究表明，补充维生素K2可减轻动脉粥样硬化的进展以及冠状动脉钙化。缺乏支持在患者中产生这种效果的临床研究。然而，非处方维生素K2补充剂的使用有所增加，并且有几篇手稿建议在接受长期华法林治疗的患者中使用它以减轻冠状动脉钙化。然而，尚不清楚在接受华法林或他汀类药物治疗的动脉粥样硬化患者中是否会出现这种情况，以及减轻冠状动脉钙化对心血管结局是有益还是有害。
