无创性超声测定冠状动脉支架术后再狭窄患者血管内皮功能和循环内皮祖细胞水平

Noninvasive ultrasound evaluation of vascular endothelial function and circulating endothelial progenitor cells on restenosis after percutaneous coronary intervention

目的运用无创性超声诊断技术测定经皮冠状动脉介入术(PCI)治疗急性心肌梗死(AMI)愈后冠状动脉支架再狭窄(ISR)患者的血管内皮功能,并探讨血管内皮功能与循环内皮祖细胞(EPCs)水平变化特点。方法选取2009—2015年川北医学院附属医院收治的完成冠状动脉造影随访的急性心肌梗死(AMI)后行PCI治疗患者220例。29例患者PCI治疗AMI后发生ISR(ISR组),191例患者PCI治疗AMI后未发生ISR(非ISR组)。采用高频超声技术获取患者肱动脉内皮依赖性功能(FMD)、非内皮依赖性功能(NMD)和颈动脉内膜中层厚度(IMT),同时检测循环EPCs表达水平。用独立样本t检验比较ISR组与非ISR组患者IMT、FMD、NMD、CD133+/KDR+EPCs、CD34+/KDR+EPCs、CD34+EPCs、CD133+EPCs、KDR+EPCs水平差异;采用单因素及多因素非条件Logistic回归分析筛选冠状动脉ISR的独立预测因子。结果 ISR组患者糖化血红蛋白(Hb A1c)、尿素氮、肌酐浓度均高于非ISR组患者,且差异均有统计学意义(t值分别为-1.769、-3.671、2.77,P均<0.05),血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂、周围血管扩张剂、胰岛素、利尿剂使用率均高于非ISR组患者,硝酸甘油使用率低于非ISR组患者,且差异均有统计学意义(χ2值分别为3.832、6.567、2.072、16.540、4.949,P均<0.05)。2组患者IMT、FMD差异均无统计学意义,但ISR组患者NMD低于非ISR组患者,且差异有统计学意义(t=2.338,P均<0.05)。2组患者CD34+EPCs、CD133+EPCs水平差异均无统计学意义;ISR组患者CD34/KDR+EPCs、CD133/KDR+EPCs、KDR+EPCs水平均较非ISR组患者降低,且差异均有统计学意义(t值分别为2.298、3.986、2.106,P均<0.05)。Logistic回归分析结果显示,Hb A1c浓度、硝酸甘油使用率、利尿剂使用率、NMD是ISR的独立预测因子。结论阶段性血糖水平等危险因素控制不良,损害血管壁功能,减少循环EPCs数量,结合老年冠状动脉粥样硬化性心脏病患者置入支架的特定人群和临床用药合理性等因素综合作用下,促进PCI后ISR发生。高频超声技术可以快速、无创测定血管内皮功能,间接反映冠状动脉受损情况,在PCI后ISR发生的风险因素评估中准确评价血管结构和功能变化,为临床治疗提供重要的诊断和治疗依据。

Objective To investigate the changes of vascular endothelium function detected by noninvasive ultrasound and circulating endothelial progenitor cells（EPCs） on in-stent restenosis（ISR） after percutaneous coronary intervention（PCI） in patients with acute myocardial infarction（AMI）. Methods Totally 220 AMI patients with previous PCI and coronary angiography follow-up（3-147 months） were recruited from medical outpatient and inpatient clinic. All patients were divided into ISR（n=29） and non ISR（n=191） group. Endothelium-dependent flow-mediated dilation（FMD）, nitroglycerin mediated dilatation（NMD）, intima-media thickness（IMT） and circulating EPCs levels were measured by flow cytometry and echocardiography. IMT, FMD, NMD, CD133/KDR ＋ EPCs, CD34/KDR ＋ EPCs, CD34 ＋ EPCs, CD133 ＋ EPCs, KDR ＋ EPCs were compared using an independent sample t-test between the two groups（ISR and non ISR）. To assess which factors were associated with ISR, statistical analysis was performed through single and multiple factors unconditioned logistic regression analysis. Results Compared with non ISR patients, ISR patients had significantly unfavorable results on Hb A1 c, urea nitrogen and creatinine（t value=-1.769,-3.671 and 2.77 respectively, all P〈0.05）, and received more intensive treatment of ACEI/ARB, insulin, vasodilator and diuretics（χ2 value=3.832, 6.567, 2.072, 16.540 and 4.949 respectively, all P〈0.05）. Meanwhile, there were no difference on IMT and FMD between ISR and non ISR groups. However, patients with ISR had lower NMD compared with non ISR patients（t value=-2.338, P〈0.05）. Patients with ISR had lower circulating CD34/KDR ＋ EPCs, CD133/KDR ＋ EPCs and KDR ＋ EPCs counts compared with non ISR patients（t value=2.298, 3.986, 2.106 respectively, all P〈0.05）. Logistic regression analysis revealed that Hb A1 c, NMD, diuretics and glyceryl trinitrate were independent predictors of ISR. Conclusions Cardiovascular risk factors, including poor control of Hb A1 C, damaged arterial smooth muscle, declined vascular function, and reduced circulating CD34/KDR ＋ EPCs, CD 133/KDR ＋ EPCs and KDR ＋ EPCs, promoted the development of ISR after percutaneous coronary intervention in elderly patients with PCI. High-frequency ultrasound technology can be a fast, non-invasive method in measurement of endothelial function indirectly reflecting the damage of coronary artery, and can be used as a perfect tool to monitor the changes of peripheral vascular function and provide important information on risk prediction in patients after PCI.