Fusaro Maria, Tripepi Giovanni, Noale Marianna, Plebani Mario, Zaninotto Martina, Piccoli Antonio, Naso Agostino, Miozzo Davide, Giannini Sandro, Avolio Marco, Foschi Annalisa, Rizzo Maria Antonietta, Gallieni Maurizio
CNR, Institute of Neuroscience - Padova, Italy.
Curr Vasc Pharmacol. 2015;13(2):248-58. doi: 10.2174/15701611113119990146.
Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4). Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 µg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 µg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046). In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.
华法林会抑制参与骨矿化和预防血管钙化的维生素K依赖性蛋白（骨钙素BGP、基质Gla蛋白MGP）。在这项为期3年随访的多中心横断面研究中，分析了18个透析单位中387例接受血液透析≥1年患者的数据。将接受华法林治疗超过1年的患者（占总人群的11.9%）与其余队列在椎体骨折、血管钙化和死亡率方面进行比较。通过腰椎X线片（D5至L4）检查椎体骨折和血管钙化情况。与对照组相比，接受华法林治疗的男性患者椎体骨折更多（77.8%对57.7%，p<0.04），但女性并非如此（42.1%对48.4%，p=0.6）；总骨钙素水平显著降低（82.35对202μg/L，p<0.0001），接受治疗的男性水平更低（69.5对女性117.0μg/L，p=0.03）。在多因素逻辑回归分析中，使用华法林与主动脉钙化（OR 2.58，p<0.001）和髂骨钙化（OR 2.86，p<0.001）几率增加相关；确定的混杂因素有年龄、心房颤动、心绞痛、使用质子泵抑制剂和总骨钙素。在2.7±0.5年的随访期间有77例患者死亡。在单因素Cox回归分析中，与未接受治疗的患者相比，接受华法林治疗的患者全因死亡风险更高（HR 2.42，95%CI 1.42 - 4.16，p=0.001），对混杂因素进行数据调整后减弱但仍证实了华法林与死亡率之间的显著关联（HR：1.97，95%CI：1.02 - 3.84，P=0.046）。对于血液透析患者，有必要进行更多研究以验证华法林的风险/效益比，其似乎与显著的发病率和死亡率增加相关。
