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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

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Abstract

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 pregnancy-associated 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.

概要

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.

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Authors and Affiliations

Authors

Contributions

Fa-chao CHEN performed the experimental research and data analysis, and wrote and edited the manuscript. Yin-chuan XU and Zhao-cai ZHANG participated in the study design, data analysis, and writing and editing of the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Corresponding authors

Correspondence to Yin-chuan Xu or Zhao-cai Zhang.

Ethics declarations

Fa-chao CHEN, Yin-chuan XU, and Zhao-cai ZHANG declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Written informed consent was required from all participants or their legal proxies before registration for being included in the study.

Additional information

Project supported by the Zhejiang Provincial Natural Science Foundation of China (No. LQ16H020003) and the National Natural Science Foundation of China (Nos. 81971860 and 81772110)

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Chen, Fc., Xu, Yc. & Zhang, Zc. Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis. J. Zhejiang Univ. Sci. B 21, 537–548 (2020). https://doi.org/10.1631/jzus.B2000049

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  • DOI: https://doi.org/10.1631/jzus.B2000049

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