急性冠状动脉综合征和稳定性冠状动脉疾病患者血清miR-133a水平变化的初步探讨

Altered levels of serum miR.133a in acute coronary syndrome and stable coronary artery disease patients

目的探讨急性冠状动脉综合征（ACS）和稳定性冠状动脉性心脏病（SCAD）患者血清miR-133a的水平变化及临床价值。方法回顾性研究。选取2011年10月至2012年10月期间南京军区南京总医院住院的64例ACS、62例SCAD患者及70名常规体检的健康对照者，其中ACS和SCAD根据欧洲心脏病学会发布的诊断标准；采用TaqMan实时荧光定量PCR技术检测血清miR-133a水平；同时分析其血脂、心肌损伤指标及冠状动脉疾病Gensini积分；采用ROC曲线分析计算曲线下面积（AUC）及其95％置信区间（CI），多项Logistic回归分析计算风险比（OR）值及其95％CI。结果与健康对照者[ACt：1．004-0．05]相比，ACS[ACt：2．34±0．24]（t=6．059，P〈0．001）和SCAD[ACt：1．45±0．13]（t=3．265，P=0．001）患者血清miR-133a水平均显著升高，且ACS患者miR-133a水平显著高于SCAD患者（t=3．133，P=0．002）。相关性分析显示，ACS和SCAD患者血清miR-133a水平与心肌型肌酸激酶同工酶（CK-MB）（r=0．402，P〈0．001）、肌钙蛋白I（cTNI）（r=0．410，P=0．001）及Gensini积分（r=0．438，P〈0．001）呈正相关。ROC曲线分析显示，血清miR-133a区分冠状动脉疾病（CAD）患者与健康对照者的AUC为0．717（95％CI：0．645～0．788，P〈0．001）；区分ACS与SCAD患者的AUC为0．667（95％CI：0．573～0．761，P=0．001）。Logistic回归分析显示，在校正了年龄、性别及血脂水平的影响后，血清miR-133a水平的升高与ACS（OR=6．00，95％CI：1．93～18．67，P=0．002）、SCAD（OR=2．81，95％CI：1．03～7．68，P=0．044）的发生相关，且对ACS、SCAD的区分具有显著意义（OR=2．13，95％CI：1．20-3．78，P=0．010）。结论CAD患者血清miR-133a水平显著升高，且ACS患者的水平变化较SCAD患者更为显著；血清miR-133a可能是CAD病情评估与判断的潜在标志物。

Objective To investigate altered levels and clinical significance of serum miR-133a in patients with acute coronary syndrome （ACS） and stable coronary artery disease （SCAD）. Methods Retrospective study. Serum miR-133a levels were determined by TaqMan quantitative reverse-transcription PCR assay in 64 ACS, 62 SCAD patients who were admitted to Jinling Hospital from October 2011 to October 2012 and 70 normal controls who had contemporaneously visited Jinling Hospital for routine examination. The ACS and SCAD patients were diagnosed according to the European Society of Cardiology guidelines. Serum lipid/lipoprotein profiles, myonecrosis biomarkers and Gensini scores were also analyzed. The area under curve （AUC） and 95% confidence interval （CI） were calculated using ROC analyses. The odds ratio （OR） and 95% CI were calculated using the multivariate logistic regression analyses. Results Compared with the controls [ △Ct ： 1.00 ±0. 05 ] , serum miR-133a levels were significantly increased in both ACS [ △Ct ： 2. 34±0.24] （t=6.059, P〈0. 001） and SCAD [△Ct： 1.45±0. 131 （t=3.265, P=0.001） patients. The miR-133a levels in ACS patients were significantly higher than in SCAD patients （t = 3. 133, P = 0. 002）. Serum miR-133a were positively correlated with levels of creatine kinase MB （CK-MB） （r = 0. 402, P 〈 0. 001 ）, cardiac troponin I （cTNI） （ r = 0. 410, P = 0. 001 ） and Gensini scores （ r =0. 438, P 〈 0. 001 ）. ROC curve analyses showed that the AUC of miR-133a for differentiating coronary artery disease （CAD） and controls was O. 717 （95% CI： 0. 645 -0. 788, P 〈0. 001 ） and the AUC for differentiating ACS and SCAD was 0. 667 （95% CI： O. 573 - O. 761, P = 0. 001 ）. Logistic regression analyses revealed that high miR- 133a levels were closely associated with the presence of ACS （ OR = 6. 00, 95% CI： 1.93 - 18.67, P = 0. 002） and SCAD （ OR = 2. 81, 95% CI： 1.03 - 7. 68, P = 0. 044 ）, and also had statistical significance for differentiating ACS and SCAD （ OR = 2. 13, 95% CI： 1.20 - 3.78, P = 0. O10）, after adjustment for the age, gender and serum lipid/lipoprotein levels. Conclusions Serum miR-133a levels were significantly elevated in CAD patients, and ACS patients exhibited the more significant increase. Serum miR-133a may be function as the potential biomarker for the disease assessment and judgement.