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目的了解阿司匹林和华法林抗栓治疗对非瓣膜病心房颤动(房颤)患者的内皮功能的影响。方法选择45～80岁的非瓣膜病持续性房颤患者106例,随机分为阿司匹林组和华法林组,分别给予阿司匹林150mg/d和调整剂量华法林(INR1·5～2·5)治疗并随访1年。于治疗前、治疗后6月和12月,采用放射免疫分析法(RIA法)测定内皮素(ET-1)和6-酮-前列腺素F1α(6-k-PGF1α)水平,采用酶联免疫吸附双抗体夹心法(ELISA法)测定血管性血友病因子(vWF)水平,进行前后比较分析。对可能影响ET-1、vWF和6-k-PGF1α水平变化的因素,包括年龄、性别、体质量指数、合并疾病、合并用药、血小板数、肌酐、尿酸、血糖、胆固醇、三酰甘油、内皮功能指标治疗前水平和抗栓药物等因素进行Pearson相关分析和多元线性回归分析。随访中观察有无脑血管和外周血管血栓栓塞和出血并发症发生。结果(1)治疗后阿司匹林降低ET-1[(111·2±79·3)比(56·7±14·6)ng/L],华法林也有同样降低ET-1作用[(128·2±78·8)比(65·4±30·8)ng/L](P均<0·05),并保持到12月。治疗后两组的vWF水平均无显著变化。阿司匹林降低6-k-PGF1α[(193·0±106·2)vs(144·6±101·1)ng/L](P<0·05),华法林对6-k-PGF1α水平无影响。(2)Pearson相关分析发现,治疗前后ET-1和vWF的变化幅度均与各自治疗前水平呈正相关(P均<0·01)。多元线性回归分析发现,治疗前ET-1水平(P=0·001)和vWF水平(P=0·004)是影响治疗后该指标变化的主要因素。(3)随访期间无血栓栓塞和严重出血并发症发生。结论阿司匹林150mg/d和调整剂量华法林(INR1·5～2·5)抗栓治疗能不同程度地改善非瓣膜病房颤患者的内皮功能。华法林低强度抗凝治疗安全有效。
Objective To investigate the effects of aspirin and warfarin antithrombotic therapy on endothelial function in patients with nonvalvular atrial fibrillation (AF). Methods A total of 106 patients with non-valvular persistent AF aged 45 to 80 years were randomly divided into aspirin group and warfarin group. The patients were given aspirin 150mg / d and adjusted dose warfarin (INR 1.5-2.5) Treatment and follow-up 1 year. The levels of endothelin (ET-1) and 6-keto-prostaglandin F1α (6-k-PGF1α) were measured by radioimmunoassay (RIA) before treatment and at 6 and 12 months after treatment. Adsorption double antibody sandwich method (ELISA) determination of von Willebrand factor (vWF) levels, before and after comparative analysis. Factors that may affect the levels of ET-1, vWF and 6-k-PGF1α, including age, sex, body mass index, comorbidity, combination therapy, platelet count, creatinine, uric acid, blood glucose, cholesterol, triglyceride, Pearson correlation analysis and multivariate linear regression analysis were performed on the level of pre-treatment index and antithrombotic drugs. During follow-up, we observed the occurrence of cerebrovascular and peripheral vascular thromboembolism and bleeding complications. Results (1) After treatment, warfarin also reduced the ET-1 level as compared with that in the aspirin group (ET · 1 [(111 · 2 ± 79 · 3) vs 56 · 7 ± 14 · 6 2 ± 78 · 8) (65 · 4 ± 30 · 8) ng / L] (all P <0.05), and maintained until December. There was no significant change in vWF levels after treatment in both groups. Aspirin decreased 6-k-PGF1α (193.0 ± 106.2 vs 144.6 ± 101.1 ng / L) (P <0.05), and warfarin had no effect on the level of 6-k-PGF1α influences. (2) Pearson correlation analysis showed that the changes of ET-1 and vWF before and after treatment were positively correlated with their pre-treatment levels (all P <0.01). Multivariate linear regression analysis showed that pretreatment ET-1 level (P = 0.001) and vWF level (P = 0.004) were the main factors influencing the change of the index after treatment. (3) no thromboembolism and severe bleeding complications during follow-up. Conclusion Aspirin 150mg / d and adjusted dose warfarin (INR 1.5 ~ 2.5) antithrombotic therapy can improve endothelial function in patients with nonvalvular atrial fibrillation to some extent. Warfarin low-intensity anticoagulant therapy is safe and effective.