Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland.
Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland; Department of Bioinformatics and Telemedicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Int J Cardiol. 2022 Oct 15;365:1-7. doi: 10.1016/j.ijcard.2022.07.034. Epub 2022 Jul 20.
Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients.
In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs).
Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1, along with lower fibrin clot permeability with no difference in CHADS-VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17-7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year).
Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.
心房颤动（AF）中会发生氧化应激增强，但其对抗凝治疗的疗效和安全性的影响尚不清楚。我们旨在评估 8-异前列腺素 F2（8-异前列腺素）水平是否与抗凝治疗的 AF 患者的临床结局相关。
在一项涉及 243 名 AF 患者（中位年龄 69 岁）的研究中，我们测量了血清 8-异前列腺素，以及血栓形成标志物，包括血浆纤维蛋白凝块通透性、凝块溶解时间（CLT）、内源性凝血酶潜能（ETP）、血管性血友病因子（VWF）和纤维蛋白溶解蛋白。在抗凝治疗期间（主要使用非维生素 K 拮抗剂口服抗凝剂（NOAC）），中位随访 53 个月期间记录了缺血性脑血管事件、大出血和死亡。
在女性、高血压患者和阵发性或持续性 AF 患者中观察到 8-异前列腺素水平升高。与 8-异前列腺素<250pg/ml（下四分位数）的患者相比，8-异前列腺素水平≥559pg/ml（上四分位数）的患者纤维蛋白原更高，VWF 更低，纤溶酶原激活物抑制剂 1 更高，纤维蛋白凝块通透性无差异，CHADS-VASc 评分、CLT 或 ETP 无差异。发生血栓栓塞事件的患者（n=20，1.9%/年）的 8-异前列腺素浓度比其余患者高 48.6%（P<0.01）。基于最佳截断值，8-异前列腺素>459pg/ml 与随访期间的血栓栓塞事件相关（风险比 2.87，95%置信区间 1.17-7.03，P=0.02）。8-异前列腺素与大出血（2.0%/年）或全因死亡率（1.9%/年）之间无关联。
尽管在 AF 患者中进行了抗凝治疗，但通过改变纤维蛋白凝块结构导致的 8-异前列腺素水平升高与血栓栓塞事件有关。
