Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, University of Murcia, Murcia, Spain.
J Am Coll Cardiol. 2011 Jun 21;57(25):2496-504. doi: 10.1016/j.jacc.2010.12.033. Epub 2011 Apr 14.
The purpose of this study was to evaluate the prognostic value of plasma von Willebrand factor (vWF) levels and fibrin d-dimer in a large cohort of anticoagulated permanent atrial fibrillation (AF) patients.
In nonanticoagulated AF patients, plasma vWF levels have been related to stroke and vascular events. There are limited data on the prognostic role of biomarkers in anticoagulated AF patients in relation to adverse events (including thromboembolism), mortality, and major bleeding.
We studied 829 patients (50% male; median age 76 years) with permanent AF who were stabilized (for at least 6 months) on oral anticoagulation therapy (international normalized ratio: 2.0 to 3.0). Plasma d-dimer and vWF levels were quantified by enzyme-linked immunosorbent assay. Patients were followed for 2 years, and adverse events (thrombotic and vascular events, mortality, and major bleeding) were recorded.
Patients were followed for a median of 828 days (range 18 to 1,085 days). On multivariate analysis, age 75 years and older, previous stroke, heart failure, and high plasma vWF levels (≥ 221 IU/dl) were associated with future adverse cardiovascular events (all p values <0.05). High plasma vWF levels, elderly patients, diabetes, hypercholesterolemia, and current smoking were associated with mortality (all p values <0.05). High plasma vWF levels were also an independent predictor of major bleeding (hazard ratio: 4.47, 95% confidence interval: 1.86 to 10.75; p < 0.001). High plasma vWF levels were able to refine clinical risk stratification schema for stroke (CHADS₂ [Congestive heart failure, Hypertension, Age ≥ 75, Diabetes mellitus, and prior Stroke or transient ischemic attack (doubled)], CHA₂DS₂-VASc [Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65 to 74 years, Sex category]) and bleeding (HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly]). d-dimer did not show any significant impact on adverse events.
High plasma vWF levels (≥221 IU/dl) are an independent risk factor for adverse events in anticoagulated permanent AF patients. This biomarker may potentially be used to refine stroke and bleeding clinical risk stratification in AF.
本研究旨在评估大样本抗凝永久性房颤（AF）患者血浆血管性血友病因子（vWF）水平和纤维蛋白 d-二聚体的预后价值。
在未抗凝的 AF 患者中，血浆 vWF 水平与卒中及血管事件相关。关于与不良事件（包括血栓栓塞、死亡率和大出血）相关的抗凝 AF 患者的生物标志物的预后作用，相关数据有限。
我们研究了 829 名（50%为男性；中位年龄 76 岁）接受口服抗凝治疗（国际标准化比值 2.0 至 3.0）稳定的永久性 AF 患者。通过酶联免疫吸附试验定量测定血浆 d-二聚体和 vWF 水平。对患者进行了 2 年的随访，记录不良事件（血栓性和血管事件、死亡率和大出血）。
患者中位随访 828 天（范围 18 至 1085 天）。多变量分析显示，年龄 75 岁及以上、既往卒中、心力衰竭和高血浆 vWF 水平（≥221IU/dl）与未来不良心血管事件相关（所有 p 值均<0.05）。高血浆 vWF 水平、老年患者、糖尿病、高胆固醇血症和当前吸烟与死亡率相关（所有 p 值均<0.05）。高血浆 vWF 水平也是大出血的独立预测因子（危险比：4.47，95%置信区间：1.86 至 10.75；p<0.001）。高血浆 vWF 水平还能细化卒中（充血性心力衰竭、高血压、年龄≥75 岁、糖尿病和既往卒中或短暂性脑缺血发作（加倍）、CHA₂DS₂-VASc[充血性心力衰竭、高血压、年龄≥75 岁、糖尿病、卒中、血管疾病、65 岁至 74 岁、性别类别]）和出血（HAS-BLED[高血压、肾功能/肝功能异常、卒中、出血史或倾向、国际标准化比值不稳定、老年、同时使用药物/酒精]）临床风险分层方案。d-二聚体对不良事件无显著影响。
高血浆 vWF 水平（≥221IU/dl）是抗凝永久性 AF 患者不良事件的独立危险因素。该生物标志物可能有助于细化 AF 患者的卒中和出血临床风险分层。
