心房颤动患者血浆miRNA-1和miRNA-155检测在复律后复发预测的应用研究

Application of Plasma miRNA-1 and miRNA-155 in Predicting Relapse after Cardioversion for Atrial Fibrillation

目的探讨血浆miRNA-1和miRNA-155检测在心房颤动患者复律后复发预测中的临床应用价值。方法收集2015年10月~2017年11月于西安市第八医院和咸阳市中心医院心内科住院治疗的110例房颤患者的血液及临床资料(复律组110例,复发组30例,未复发组80例),比较分析三组患者血浆miRNA-1和miRNA-155表达水平的变化与房颤复发的关系。两标志物的表达采用实时逆转录-聚合酶链反应(RT-PCR)技术检测。应用心动超声仪评价患者的左房内径及左心室射血分数。采用罗氏MODULARP800全自动生化分析仪检测患者的空腹血糖及总胆固醇水平。建立受试者工作特征曲线(ROC曲线)评价miRNA-1和miRNA-155在房颤复发中的临床意义。结果血浆miRNA-1和miRNA-155在未复发组、复律组和复发组的水平分别为0.38±0.09,0.39±0.08,0.82±0.15和0.87±0.17,0.85±0.18,0.21±0.05。它们在复发组的表达与未复发组和复律组分别比较明显上调、下调(t=21.37,20.57,均P<0.01;t=18.77,11.71,均P<0.01),而在未复发组与复律组的表达比较差异无统计学意义(t=0.67,0.54,均P>0.05)。房颤患者的收缩压、血清总胆固醇水平(TC)、左房内径、空腹血糖水平(FBG)和左室射血分数(EF)分别在未复发组、复律组和复发组的检测结果为(133±7mmHg,3.87±0.73mmol/L,44.97±6.82mm,4.13±0.57mmol/L,61.20%±7.38%),(134±6mmHg,3.98±0.70mmol/L,45.50±6.72mm,4.17±0.46mmol/L,61.07%±7.19%),(145±7mmHg,4.03±0.71mmol/L,58.97±7.33mm,4.20±0.50mmol/L,60.30%±7.21%)。复发组的左心房内径和收缩压分别与复律组和未复发组比较显著增高(t=6.69,10.23,P<0.01;t=8.42,15.53,P<0.01);而复律组的两项指标分别与未复发组比较差异均无统计学意义(t=0.73,0.27,均P>0.05);各组间的TC,FBG和EF比较,差异均无统计学意义(t=0.58,0.61,0.52,均P>0.05;t=0.65,0.58,0.41,均P>0.05;t=0.61,0.41,0.52,均P>0.05)。在复发组中,miRNA-1和miRNA-155表达具有负相关(r=-0.673,P<0.01),且它们分别与左心房内径、收缩压也具有相关性(r=0.528,-0.537),均P<0.01。ROC曲线的分析中,复发组分别以复律组和未复发组为参照,血浆miRNA-1的AUC分别为0.743(95%CI:0.627~0.839),P<0.01;0.730(95%CI:0.21~0.826),P<0.01,血浆miRNA-155的AUC分别为0.703(95%CI:0.628~0.837),P<0.01;0.685(95%CI:0.603~0.813),P<0.01。结论血浆miRNA-1和miRNA-155检测可应用于房颤患者复律后复发的预测,并成为房颤复发有效的预警标志物和干预靶点。

Objective To investigate the application of plasma miRNA-1 and miRNA-155 in predicting recurrence after cardio- version for atrial fibrillation. Methods The blood and clinical data of 110 patients with atrial fibrillation in Department of Cardiology hospitalized from the Eighth Hospital of Xi＇an and Central Hospital of Xianyang from October 2015 to Novem- ber 2017 were collected （110 cases in cardioversion group, 30 cases in relapse group and 80 cases in non-recurrence group）. The relationship between the changes of miRNA-1 and miRNA-155 expression levels in plasma in the three groups,and the recurrence of atrial fibrillation were compared and analyzed. Expression of two markers was detected via real-time reverse transcription polymerase chain reaction （RT-PCR）, The left atrial diameter and left ventricular ejection fraction were evalua- ted by echocardiography. The fasting blood glucose and totalcholesterol were detected using Roche MODULARP800 auto- matic biochemical analyzer. The receiver operating characteristic curve （ROC curve） was established to evaluate the clinical significance of miRNA-1 and miRNA-155 in the recurrence of atrial fibrillation. Results The levels of plasma miRNA-1 and miRNA-155 in the non recurrent group, the cardioversion group and the recurrent group were （0.38 ± 0. 09,0. 39±0. 08, 0.82±0.15） and （0.87±0.17,0.85±0.18,0.21±0.05） ,which in the recurrent group was significantly up and down com- pared with in the non-recurrent and cardioversion groups, respectively （t = 21.37,20.57, P 〈 0. 01 ;t = 18.77,11.71, P 〈 0.01）. Nevertheless,no differences of the two markers were observed between the non recurrent group and the cardioversion group（t= 0.67, 0. 54, P〉 0.01）. These outcomes of systolic pressure, serum total cholesterol level （TC）, left atrial diame- ter, fasting blood glucose level （FBG） and left ventricular eiection fraction （EF） in non recurrent group,cardioversion group and recurrent group were （133 4- 7 mmHg, 3.87 ± 0.73 mmol/L, 44.97 ± 6.82 mm, 4.13 ± 0.57 mmol/L, 61.20%± 7.38%）,（134±6 mmHg,3. 98±0.70 mmol/L,45. 50±6.72 mm,4. 17±0.46mmol/L,61.07% ±7.19%//00）, （145±7 mm- Hg,4. 03±0.71 mmol/L,58. 97±7.33 mm,4. 20±0.50 mmol/L,60. 30%±7.21%）. Interestingly,these evident incresces of left atrial diameter and systolic pressure were clarified for the recurrent patients following these statistical differences （t= 6.69,10.23,P〈0.05 ;t=8. 42,15. 53 ,P〈0.05）,and observations of no differences were described for them between the cardioversion group and the non recurrent group （t= 0.27, 0. 73, P〉0. 05）. In addition, these presences of TC, FBG and EF in the three group were shown to be not statistically significant （t = 0.58,0.61,0.52, P〉0.05 ; t = 0. 65,0. 58,0. 41, P 0. 05;t=0. 61,0. 41,0. 52,P〉0. 05）. In the recurrent group,the expression of miRNA-1 and miRNA-155 was revealed to present a negative correlation （r=-0. 673 ,P〈0.01）,and to be correlated with the left atrium diameter and systolic pres- sure, respectively （r= 0. 528, - 0.537, P〈0.01）. According to analysis of ROC curve, the data in the recurrence group was taken these in the eardioversion group and the non recurrent group as a reference,the AUC of plasma miRNA-1 was 0. 743 （95%CI：0. 627±0. 839）,P〈0.01±0. 730（95%CI：0.21±0. 826）,P〈0.01, and the AUC of the plasma miRNA-155 was 0. 703（95%CI：0. 628±0. 837）,P〈0.01;0. 685（95%C1：0. 603±0. 813）,P〈0.01,respectively. Conclusion Detection of plasma miRNA-1 and miRNA-155 can be used predicting recurrence of atrial fibrillation patients after cardioversion,and be- come an effective early warning marker and intervention target for recurrence of atrial fibrillation.