Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis

预测脓毒症患者心脏功能障碍和死亡率的多生物标记物策略

Objective:The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic patients.Methods:Brain natriuretic peptide(BNP),cardiac troponin I(cTnI),and heart-type fatty acid-binding protein(h-FABP)in 147 septic patients were assayed within 6 h after admission.We also determined the plasma levels of myeloperoxidase(MPO)and pregnancyassociated plasma protein-A(PAPP-A).The receiver operating characteristic(ROC)curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality.Also,the ROC curve,net reclassification improvement(NRI),and integrated discrimination improvement(IDI)indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.Results:Our statistics revealed that only h-FABP independently predicted SIMD(P<0.05).The addition of MPO and cTnI to h-FABP for SIMD prediction provided an NRI of 18.7%(P=0.025)and IDI of 3.3%(P=0.033).However,the addition of MPO or cTnI to h-FABP did not significantly improve the predictive ability of h-FABP to SIMD,as evidenced by the area under the curve(AUC),NRI,and IDI(all P>0.05).A history of shock and MPO were independent predictors of mortality in septic patients(both P<0.05).The addition of PAPP-A and h-FABP to MPO resulted in a mortality prediction with NRI of 25.5%(P=0.013)and IDI of 2.9%(P=0.045).However,this study revealed that the addition of h-FABP or PAPP-A to MPO did not significantly improve the ability to predict mortality,as evidenced by the AUC,NRI,and IDI(all P>0.05).Conclusions:The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.

目的:评估联合应用多种生物标记物以预测脓毒症患者早期心脏功能障碍及28天死亡率的可行性。创新点:(1)通过净重分类改善(NRI)和综合辨别改善(IDI)指标,评估多种生物标志物策略相比单一生物标志物策略对脓毒症患者心脏功能障碍及28天死亡率的预测价值。(2)评估心脏型脂肪酸结合蛋白(h-FABP)、髓过氧化物酶(MPO)以及妊娠相关血浆蛋白A(PAPP-A)等新型生物标记物在脓毒症中的临床预测价值。方法:检测147例脓毒症患者在入院后6小时内血浆中脑钠肽(BNP)、心肌肌钙蛋白I(cTnI)、h-FABP、MPO及PAPP-A的水平。使用受试者工作特征(ROC)曲线来评估各种单一生物标志物在脓毒症患者心脏功能障碍诊断和28天死亡率预测中的最佳截止值。采用ROC曲线、NRI和IDI指标评估多种生物标志物策略相比单一生物标志物策略在预测脓毒症相关心脏功能障碍及28天死亡率中的价值。结论:MPO、cTnI和h-FABP联合应用显著提高了对脓毒症患者心脏功能障碍的预测能力,同时PAPP-A、MPO和h-FABP联合应用显著提高了预测脓毒症患者28天死亡率的能力。