CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada.
CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada.
Nephrol Dial Transplant. 2014 Nov;29(11):2113-20. doi: 10.1093/ndt/gfu224. Epub 2014 Jun 18.
Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu.
Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median.
At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01).
This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.
在晚期慢性肾脏病患者中，主动脉僵硬的加速进展不能用传统的心血管危险因素很好地解释。我们假设维生素 K 缺乏可能导致在促钙化尿毒症环境中主动脉僵硬的加速进展。
18 名接受华法林治疗的血液透析 (HD) 患者与 54 名未接受华法林治疗的 HD 患者（对照组）相匹配。在平均 1.2 年的随访后，通过颈动脉-股动脉脉搏波速度 (cf-PWV) 确定主动脉僵硬。在对照组中，自发维生素 K 缺乏被定义为维生素 K 缺乏/不存在诱导的蛋白质 II >中位数。
基线时，临床特征和 cf-PWV 相似。对照组 cf-PWV 增加 0.86 ± 1.87 m/s，华法林组增加 2.24 ± 2.68 m/s（P = 0.024）。调整混杂因素后，华法林治疗与主动脉僵硬的进展独立相关（P = 0.016）。主动脉僵硬进展的速度与维生素 K 状态和华法林治疗呈线性趋势，表明至少部分作用是通过减少维生素 K 的可用性介导的。华法林治疗对死亡率的未调整和调整后的危险比 (HR) 分别为 2.40（P = 0.006）和 2.53（P = 0.006）。在前向条件 Cox 回归分析中，年龄、白蛋白、增强指数 (AIx) 和随访时 cf-PWV > 13.8 m/s（HR：2.11，P = 0.05）是死亡率的独立决定因素，而华法林的使用并未保留为独立因素。最后，与维生素 K 状态较好的对照组和服用华法林的患者相比，维生素 K 状态较差的对照组患者的生存情况处于中间水平（P = 0.01）。
这是第一项表明华法林、功能性维生素 K 缺乏与 HD 患者主动脉僵硬进展之间存在时间关联的研究。这些发现表明，长期华法林治疗的净心血管益处可能需要在该人群中重新评估。
