血液透析患者颈动脉内中膜厚度与血栓调节蛋白、炎症因子及心血管疾病的关联

摘要

目的:探讨维持性血液透析(MHD)患者颈动脉内中膜厚度(cIMT)与血栓调节蛋白(Tm)和炎症因子之间的关系,及其对心血管疾病(CVD)的影响. 方法:选择透析龄≥3月的MHD患者108例,采用超声检测cIMT,ELISA法检测血浆Tm、炎症因子[白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)]水平,观察Tm、炎症因子及临床指标对cIMT的影响.随访12个月,Logistic回归分析MHD患者发生CVD的危险因素.受试者工作特征(ROG)曲线分析cIMT、Tm对预测CVD的价值. 结果:108例MHD患者中,83例(76.9％)存在cIMT增厚;与无cIMT增厚患者相比,重度cIMT增厚患者血浆Tm水平显著升高[(20.43±3.22) mg/Lvs(7.92±5.39) mg/L,P＜0.01],C反应蛋白(CRP)、IL-1β、IL-6、TNF-α水平较高,收缩压、年龄更高,差异有统计学意义(P＜0.01或P＜0.05);与轻度cIMT增厚患者相比,重度cIMT增厚患者血浆Tm、CRP、IL-6水平较高(P＜0.05);收缩压、年龄、IL-1β、TNF-α等无统计学差异.直线相关分析显示,Tm水平与IL-1β、IL-6、TNF-α、CRP均呈正相关(P＜0.05或P＜0.01).多元回归分析显示,cIMT与Tm呈独立正相关(β3=0.620,t=5.858,P＜0.001).随访12月,发生CVD 51例次,因CVD死亡9例,Logistic回归分析显示,cIMT增厚和Tm水平升高是CVD发生的独立危险因素(Wald值=7.639,OR=1.36,95％CI 1.467～9.258,P=0.019;Wald值=8.963,OR=1.04,95％ CI 2.272 ～5.009,P=0.03).ROC曲线显示,cIMT预测CVD的曲线下面积(AUC)为0.866(95％CI 0.794 ～0.939,P=0.001),临界值为1.96mm;Tm预测CVD的AUC为0.763(95％CI 0.664～0.862,P=0.003),临界值18.635 mg/L. 结论:cIMT增厚与Tm水平升高是MHD患者发生CVD的独立危险因素,提示血管内皮细胞损伤与炎症共同促进了cIMT增厚.cIMT与Tm可能对MHD患者发生CVD具有预测价值.%Objective:To investigate the association of carotid atherosclerosis with thrombomodulin (Tm) and cytokines,and explore the influence on cardiovascular events in patients with maintenance hemodialysis (MHD).Methodology:A total of 108 stable MHD patients were enrolled into this study.The bilateral common carotid artery intimamedia thickness (cIMT) and carotid artery atheromatous plaque were measured by high-resolution B-mode ultrasonography.Serum levels of Tm,cytokines (IL-1β3,IL-6 and TNF-oα) were determined by ELISA.Correlation analysis of cIMT with Tm,cytokines and other parameters was performed.Logistic regression analysis was used to determine the risk factor of CVD in MHD patients with 12 months follow-up.The predictive value of cIMT and Tm for CVD were assessed using receiver operator characteristic (ROC) curve.Results:Increased cIMT was detected in 83 (76.9％) patients.Compared with the normal cIMT patients,plasma Tm concentration was significantly increased [(20.43 ± 3.22) mg/L vs (7.92± 5.39)mg/L,P＜0.01] L in cIMT severe thickening patients,serum IL-1β,IL-6,TNF-α and CRP levels were also significantly elevated.Compared with cIMT mild thickening patients,Tm concentration was obviously higher [(20.43±3.22) mg/L vs (10.92±4.32) mg/L,P＜0.01] and CRP,IL-6 were obviously higher (P＜0.05) in cIMT severc thickening patients.Linear correlation analysis discovered that Tm concentration was positively correlated with IL-1β,IL-6,TNF-α,CRP (P＜0.05 or P＜0.01).Multiple regression analysis indicated that Tm was independent positive correlate with cIMT (β =0.620,t=5.858,P＜0.001).12 months after follow-up,there were 51 newly-happened cardiovascular events and 9 cases died.Logistic regression analysis found that increased cIMT (Wald =7.639,OR =1.36,95％ CI 1.467～ 9.258,P =0.019)and Tm (Wald=8.963,OR =1.04,95％CI 2.272-5.009,P =0.03) were risk factors to cardiovascular events.The area under the ROC curve (AUC) of cIMT for CVD was 0.866 (95％CI 0.794-0.939,P=0.001),cutoff value was 1.96 mm;The AUC of blood Tm for CVD was 0.763 (95％CI 0.664-0.862,P=0.003),cutoff value was 18.635 mg/L.Conclusion:Vascular endothelial cell injury represented by Tm concentration and cIMT thickening were risk factors for cardiovascular events in MHD patients.Vascular endothelial cell injury and micro inflammatory reaction mnay promote the occurrence of atherosclerosis in MHD patients.