ST段抬高型心肌梗死患者血浆前蛋白转化酶枯草杆菌素Kexin9型与血小板活化及经皮冠状动脉介入治疗后无复流的关系

Association between Plasma Proprotein Convertase Subtilisin/Kexin Type 9 and Platelet Activation and Angiographic No-reflow Phenomenon after Percutaneous Coronary Intervention in Patients with ST-segment Elevation Myocardial Infarction

目的 分析ST段抬高型心肌梗死(STEMI)患者血浆前蛋白转化酶枯草杆菌素Kexin9型(PCSK9)与血小板活化及经皮冠状动脉介入治疗(PCI)后无复流的关系。方法 2019年1月至2021年12月西安交通大学医学院附属三二〇一医院心血管内科共招募218例STEMI患者,顺利完成急诊PCI。将PCI后心肌梗死溶栓(TIMI)血流分级<3级定义为无复流。采用酶联免疫吸附法检测所有患者入院时血浆PCSK9水平,采用全血流式细胞术检测血小板-单核细胞聚集体(PMA)形成。结果 所有STEMI患者血浆PCSK9水平为61.10~750.75 ng/mL,中位值为279.50 ng/mL。血浆PCSK9高水平组STEMI患者PCI后无复流发生率更高,且差异有统计学意义(P <0.05)。无复流组STEMI患者PMA及血浆PCSK9水平均高于复流组STEMI患者[(36.40±8.23)%比(33.35±7.79)%,(386.12±130.46)ng/mL比(263.36±103.40)ng/mL],且差异均有统计学意义(t=2.193,P=0.029;t=6.394,P <0.001)。线性回归分析结果显示,血浆PCSK9水平与低密度脂蛋白胆固醇水平、峰值心肌肌钙蛋白I水平、PMA呈正相关(P <0.05)。Logistic回归分析结果显示,D-二聚体水平≥382 mg/L、血浆PCSK9水平≥279.50 ng/mL是STEMI患者PCI后无复流的独立危险因素(P <0.05)。受试者操作特征曲线显示,血浆PCSK9水平预测STEMI患者PCI后无复流的曲线下面积为0.766[95%置信区间(CI):0.689~0.844],显著优于D-二聚体的0.663(95%CI:0.565~0.761)(P <0.05)。结论 STEMI患者血浆PCSK9水平与血小板活化有关,PCSK9可作为预测STEMI患者无复流的生物标志物。

Objective To analyze the relationship between plasma proprotein convertase subtilisin/Kexin type 9(PCSK9)and platelet activation and angiographic no-reflow phenomenon after percutaneous coronary intervention(PCI)in ST-segment elevation myocardial infarction(STEMI)patients.Methods From January 2019 to December 2021,218 STEMI patients were recruited in the Department of Cardiology of 3201 Hospital Affiliated to Medical College of Xi'an Jiaotong University to successfully complete primary PCI.The post-PCI thrombolytic therapy(TIMI)blood flow grade<3 was defined as angiographic no-reflow phenomenon.Plasma PCSK9 level was detected by enzyme-linked immunosorbent assay at admission,and the formation of platelet monocyte aggregates(PMA)was detected by whole blood flow cytometry.Results The median plasma PCSK9 level of all STEMI patients was 279.50 ng/mL(61.10-750.75 ng/mL).The incidence of no-reflow after PCI was significantly higher in patients with high level of PCSK9 subgroup(P<0.05).PMA([36.40±8.23]%vs.[33.35±7.79]%,t=2.193,P=0.029)and plasma PCSK9([386.12±130.46]ng/mL vs.[263.36±103.40]ng/mL,t=6.394,P<0.001)in patients with no-reflow were significantly higher than those in patients with reflow.By linear regression analysis,the plasma PCSK9 level was positively correlated with low density lipoprotein cholesterol,peak cardiac troponin I and PMA(P<0.05).Logistic regression analysis showed that D dimer≥382 mg/L and plasma PCSK9≥279.50 ng/mL were independent risk factors for no-reflow phenomenon after PCI in STEMI patients(P<0.05).The area under the curve that predicted the angiographic no-reflow phenomenon after PCI in STEMI patients by plasma PCSK9 level was 0.766(95%CI:0.689-0.844),which was significantly larger than that of D-dimer(0.663,95%CI:0.565-0.761,P<0.05).Conclusion Plasma PCSK9 level is associated with platelet activation,and PCSK9 can be used as a predictive biomarker of angiographic no-reflow phenomenon in STEMI patients.