心房颤动患者抗栓治疗中血管内皮功能的变化

The Effect of Aspirin and Warfarin on Vascular Endothelial Function in Patients with Atrial Fibrillation

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 influence of aspirin and warfarin on endothelial function in the pa-tients with non-valvular atrial fibrillation. Methods One hundred and six patients with non-valvular persistent atrial fibrillation were randomized to receive aspirin （150 mg/d） or dose-adjusted warfarin （INR 1.5-2.5） re-spectively for 1 year. The plasma level of endothelin-1 （ET-1） and 6-keto-prostaglandin Flα（6-k-PGF1α） were determined by radioimmunoassay （RIA） and the plasma level of yon Willebrand Factor （vWF） by enzyme linked immunoadsorbent assay （ELISA） before, 6 and 12 months after treatment. Results 1）Aspirin decreased ET-1 level （111.2±79.3 vs 56.7±14.6 ng/L, P〈0.05） as well warfarin （128.2±78.8 vs 65.4±30.8 ng/L, P〈0.05） with the effects sustained till 12 months. However, little changes in the level of vWF was found. The level of 6-k-PGF1α was decreased after aspirin （193.0±106.2 vs 144.6±101.1 ng/L, P〈0.05） with no changes after warfarin. After adjusting for the variables such as age, sex, BMI, count of platelet, creatinine, uric acid, blood sugar, cholesterol, triglyceride, endothelial function index before the treatment, multiple regression analysis revealed the level of ET-1（P=0.001） and vWF（P=0.004） before treatment were the independent factors affect-ing their changes after treatment. No thromboembolism and severe hemorrhage events during the follow-up was found. Conclusion Aspirin 150 mg/d and dose-adjusted warfarin（INR 1.5-2.5）improve the endothelial func-tion of patients with non-valvular atrial fibrillation with satisfied safety.