血浆受体相互作用蛋白激酶1和混合系列蛋白激酶结构域蛋白与急性冠状动脉综合征患者经皮冠状动脉介入术后主要不良心血管事件的关系

Relationships of plasma receptor interacting protein kinase 1 and mixed lineage kinase domain-like protein with major adverse cardiovascular event after percutaneous coronary intervention in patients with acute coronary syndrome

目的观察急性冠状动脉综合征(acute coronary syndrome, ACS)患者血浆受体相互作用蛋白激酶1(receptor interacting protein kinase 1, RIPK1)及混合系列蛋白激酶结构域蛋白(mixed lineage kinase domain-like protein, MLKL)水平变化,探讨其对经皮冠状动脉介入治疗(percutaneous coronary intervention, PCI)术后发生主要不良心血管事件(major adverse cardiovascular event, MACE)的预测价值。方法行PCI术的ACS患者174例为ACS组,同期体检健康者62例为对照组,采用ELISA法检测PCI术前2组血浆RIPK1和MLKL水平。ACS患者PCI术后随访1年,根据MACE发生情况分为MACE组40例与无MACE组134例,比较2组临床资料及血浆RIPK1、MLKL水平,采用多因素Cox回归分析ACS患者PCI术后发生MACE的影响因素;绘制ROC曲线,评估血浆RIPK1和MLKL水平对ACS患者PCI术后发生MACE的预测效能。结果 ACS组血浆RIPK1[(6.02±1.45)ng/L]、MLKL[(3.95±1.43)ng/L]水平均高于对照组[(1.94±0.15)、(0.53±0.07)ng/L](t=22.137,P<0.001;t=18.799,P<0.001)。MACE组有吸烟史比率(60.00%)、发病至就诊时间[(14.70±1.56)h]、血糖[(5.40±1.18)mmol/L]、低密度脂蛋白胆固醇[(2.87±0.97)mmol/L]、血浆RIPK1[(7.20±1.45)ng/L]、MLKL[(5.23±1.36)ng/L]水平均高于无MACE组[43.28%、(12.70±1.48)h、(2.87±0.97)mmol/L、(2.42±0.97)mmol/L、(5.67±1.25)ng/L、(3.57±1.22)ng/L](P<0.05),左室射血分数[(55.34±4.32)%]低于无MACE组[(59.99±4.35)%](P<0.05)。发病至就诊时间(HR=1.237,95%CI:0.993~1.540,P=0.003)、左室射血分数(HR=0.915,95%CI:0.843~0.994,P=0.035)和PCI术前血浆RIPK1(HR=1.332,95%CI:1.008~1.761,P=0.044)、MLKL(HR=1.670,95%CI:1.354~2.059,P<0.001)水平是ACS患者PCI术后发生MACE的影响因素。当血浆RIPK、MLKL水平的最佳截断值为6.27、4.06 ng/L时,二者联合检测预测ACS患者PCI术后发生MACE的AUC[0.929(95%CI:0.880~0.962,P<0.001)]大于RIPK1[0.782(95%CI:0.713~0.841,P<0.001)]、MLKL[0.811(95%CI:0.745~0.867,P<0.001)]单独检测(Z=3.100,P=0.002;Z=2.776,P=0.006),灵敏度为80.00%,特异度为89.55%,准确率为87.35%。结论 ACS患者血浆RIPK1和MLKL水平升高,PCI术前血浆RIPK1和MLKL水平升高的ACS患者PCI术后发生MACE的风险增高,二者联合检测对ACS患者PCI术后发生MACE有较高预测价值。

Objective To observe the expressions of plasma receptor interacting kinase 1 (RIPK1)and mixed lineage kinase domain-like protein(MLKL)in patients with acute coronary syndrome(ACS),and to investigate their predictive values to the occurrence of major adverse cardiovascular event(MACE)after percutaneous coronary intervention(PCI).Methods The levels of plasma RIPK1and MLKL were detected by ELISA before PCI in 174patients with ACS receiving PCI(ACS group)and 62healthy volunteers(control group).ACS patients were followed up for one year after PCI and were divided into MACE group (n=40)and no-MACE group (n=134)according to the occurrence of MACE.The clinical data and plasma RIPK1 and MLKL levels were compared between MACE group and no-MACE group.Multivariate Cox regression analysis was done to assess the influencing factors of MACE after PCI in ACS patients.ROC curve was drawn to assess the predictive efficiencies of plasma RIPK1and MLKL levels on MACE after PCI in ACS patients.Results The levels of plasma RIPK1and MLKL were higher in ACS group[(6.02±1.45),(3.95±1.43)ng/L]than those in control group[(1.94±0.15),(0.53±0.07)ng/L](t=22.137,P<0.001;t=18.799,P<0.001).MACE group had higher percentage of patients with smoking history,longer onset-to-visit time,higher levels of plasma glucose,low-density lipoprotein cholesterol,plasma RIPK1and MLKL,and lower left ventricular ejection fraction[60.00%,(14.70±1.56)h,(5.40±1.118)mmol/L,(2.87±0.97)mmol/L,(7.20±1.45)ng/L,(5.23±1.36)ng/L,(55.34±4.32)%]than no-MACE group[43.28%,(12.70±1.48)h,(2.87±0.97)mmol/L,(2.42±0.97)mmol/L,(5.67±1.25)ng/L,(3.57±1.22)ng/L,(59.99±4.35)%](P<0.05).The onset-to-visit time(HR=1.237,95%CI:0.993-1.540,P=0.003),left ventricular ejection fraction (HR=0.915,95%CI:0.843-0.994,P=0.035),preoperative level of plasma RIPK1 (HR=1.332,95%CI:1.008-1.761,P=0.044)and MLKL (HR=1.670,95%CI:1.354-2.059,P<0.001)were the influencing factors of MACE after PCI in ACS patients.When the optimal cut-off values of plasma RIPK and MLKL were 6.27ng/L and 4.06ng/L,the AUCof combined detection of them two[0.929(95%CI:0.880-0.962,P<0.001)]was greater than that of single detection of RIPK1[0.782 (95%CI:0.713-0.841,P<0.001)]and MLKL[0.811 (95%CI:0.745-0.867,P<0.001)]for predicting MACE after PCI in ACS patients (Z=3.100,P=0.002;Z=2.776,P=0.006),with a sensitivity of80.00%,a specificity of 89.55%and an accuracy of 87.35%.Conclusions Plasma RIPK1and MLKL levels increase in ACS patients,and those with increased levels of RIPK1and MLKL before PCI have an increased risk of MACE after PCI.The combined detection of plasma RIPK1and MLKL have a high predictive value to MACE after PCI in ACS patients.