可溶性ST2的检测性能评价及对心力衰竭患者的诊断价值

摘要

目的：对可溶性ST2（ sST2） ELISA双抗夹心法试剂的检测性能进行评价。初步评估sST2的临床应用价值。方法方法学评价。参考美国临床和实验室标准协会（CLSI）EP-15A、EP6-A方案对该项目的精密度、线性范围进行验证，选取上海地区5个社区的表面健康人300名（年龄20～85岁，男124名，女176名）建立参考区间，选取2013年5至7月中山医院临床诊断心力衰竭患者117例，根据美国纽约心脏病学会（ NYHA ）心功能分级结果对患者进行分组，比较患者 sST2与 NT-proBNP、左心室射血分数（ LVEF ）、NYHA心功能分级结果之间的相关性，使用ROC曲线比较血清sST2、NT-proBNP、LVEF对心力衰竭患者进行诊断及分层的能力。结果 sST2检测试剂盒批内CV＜4％、批间CV＜10％；0～200 ng/ml范围内线性良好（ Y＝0.995X＋0.005，R2＝0.999）；依据300名表面健康人血清sST2水平得出参考区间（男10.2～41.0μg/L，女8.9～28.1μg/L）。心力衰竭患者血清sST2浓度与NT-ProBNP、NYHA心功能分级相关（Spearman相关系数分别为0.301、0.413），而sST2与LVEF不相关。 sST2在NYHA心功能≤Ⅱ级与＞Ⅱ级患者中的中位数（IQR）分别为28.3（19.5～39.2）；45.1（34.1～85.6），P＜0.01。 sST2区分正常人与心力衰竭患者的AUC为0.815，诊断敏感性为51.2％，特异性为92.7％。 sST2、sST2联合 NT-ProBNP、三者联合（ sST2、NT-ProBNP、LVEF ）区分NYHA心功能≤Ⅱ级与＞Ⅱ级患者的AUC分别为0.743、0.810、0.831，三者联合后诊断敏感性增加为94.7％。结论 sST2检测试剂盒检测性能符合临床要求，临床实验表明：血清sST2与NT-ProBNP， NYHA相关。 sST2不受年龄、肾功能损害和体重指数的影响。联合sST2可以有助于NT-ProBNP与LVEF更好地区分心力衰竭患者。%Objective To evaluate the performance of sST 2 ELISA kit and investigate the clinical application of sST2.Methods This verification study validated the precision , linearity of sST2 ELISA kit according to the CLSI EP-15A, EP-6A protocols.300 healthy adults(aged from 20 to 85, 124 male and 176 female) from 5 different districts of Shanghai were used to establish serum sST 2 reference interval .The correlations between sST2, NT-ProBNP, LVEF and NYHA class were analyzed in 117 patients diagnosed with heart failure who were grouped according to the New York heart association ( NYHA).Receiver operating characteristic (ROC) curve was used to compare the ablity of sST2, NT-ProBNP, LVEF in distinguishing heart failure patients .Results The within-lot and between-lot variation of three level samples were below 4% and 10% respectively.There was a good linear correlation ( Y=0.995X+0.005, R2 =0.999) between theoretical value and actual detection result in the range of 0 to 200 μg/ml.The reference interval of sST2 was 10.2 to 41.0μg/ml for males and 8.9 to 28.1μg/ml for females.sST2 was positively correlated with NT-ProBNP and NYHA class but did not correlate with LVEF in heart failure patients . Patients with NYHA class>II (Median:28.3,IQR:19.5-39.2)had higher serum sST2 level than patients with NYHA class≤II (Median:45.1,IQR:34.1 -85.6), P<0.05.The AUC of sST2 in distinguishing heart failure patients from normal people was 0.815(sensitivity :51.2%,specificity:92.7%).The AUC of sST2 ,sST2+NT-ProBNP and sST2+NT-ProBNP+LVEF in distinguishing patients between NYHA class≤II and>II were 0.743, 0.810, 0.831 respectively and the sensitivity of sST 2 +NT-ProBNP+LVEF was 94.7%.Conclusions Experimental results show that this sST 2 ELISA kit has a good performance in the precision, linearity.sST2 correlates with NT-ProBNP and NYHA class but do not correlates with LVEF . Serum sST2 level is not influenced by age , BMI, renal function.sST2 could be a good supplement of NT-ProBNP and LVEF in distinguishing patients between NYHA class≤II and>II.