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CLC number: R541; R459.7

On-line Access: 2020-07-07

Received: 2020-02-11

Revision Accepted: 2020-03-30

Crosschecked: 2020-06-05

Cited: 0

Clicked: 1872

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Zhao-cai Zhang

https://orcid.org/0000-0002-4709-066X

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.7 P.537-548

http://doi.org/10.1631/jzus.B2000049


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


Author(s):  Fa-chao Chen, Yin-chuan Xu, Zhao-cai Zhang

Affiliation(s):  Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; more

Corresponding email(s):   2314029@zju.edu.cn, 2313003@zju.edu.cn

Key Words:  Multi-biomarker, Myocardial dysfunction, Sepsis, Mortality


Fa-chao Chen, Yin-chuan Xu, Zhao-cai Zhang. Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis[J]. Journal of Zhejiang University Science B, 2020, 21(7): 537-548.

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author="Fa-chao Chen, Yin-chuan Xu, Zhao-cai Zhang",
journal="Journal of Zhejiang University Science B",
volume="21",
number="7",
pages="537-548",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000049"
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%0 Journal Article
%T Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis
%A Fa-chao Chen
%A Yin-chuan Xu
%A Zhao-cai Zhang
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 7
%P 537-548
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000049

TY - JOUR
T1 - Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis
A1 - Fa-chao Chen
A1 - Yin-chuan Xu
A1 - Zhao-cai Zhang
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 7
SP - 537
EP - 548
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Y1 - 2020
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2000049


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.

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

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.

关键词:多种生物标志物;心脏功能障碍;脓毒症;死亡率

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]ACCP/SCCM, 1992. American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med, 20(6):864-874.

[2]Alhadi HA, Fox KAA, 2010. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction: the potential for influencing patient management. Sultan Qaboos Univ Med J, 10(1):41-49.

[3]Annane D, Bellissant E, Cavaillon JM, 2005. Septic shock. Lancet, 365(9453):63-78.

[4]Arimoto T, Takeishi Y, Shiga R, et al., 2005. Prognostic value of elevated circulating heart-type fatty acid binding protein in patients with congestive heart failure. J Card Fail, 11(1):56-60.

[5]Askari AT, Brennan ML, Zhou XR, et al., 2003. Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction. J Exp Med, 197(5):615-624.

[6]Avaliani T, Talakvadze T, Tabagari S, 2019. Prognostic value of plasma myeloperoxidase level’s and echocardiographic determinants in chronic heart failure patients. Georgian Med News, (288):55-60.

[7]Baldus S, Heeschen C, Meinertz T, et al., 2003. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation, 108(12):1440-1445.

[8]Berdal JE, Stavem K, Omland T, et al., 2008. Prognostic merit of N-terminal-proBNP and N-terminal-proANP in mechanically ventilated critically ill patients. Acta Anaesthesiol Scand, 52(9):1265-1272.

[9]Bessière F, Khenifer S, Dubourg J, et al., 2013. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med, 39(7):1181-1189.

[10]Blanco J, Muriel-Bombín A, Sagredo V, et al., 2008. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care, 12(6):R158.

[11]Charpentier J, Luyt CE, Fulla Y, et al., 2004. Brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis. Crit Care Med, 32(3):660-665.

[12]Consuegra-Sanchez L, Fredericks S, Kaski JC, 2009. Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular risk. Atherosclerosis, 203(2):346-352.

[13]Cook NR, Ridker PM, 2009. Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures. Ann Intern Med, 150(11):795-802.

[14]Dellinger RP, Levy MM, Carlet JM, et al., 2008. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med, 34(1):17-60.

[15]Fromm RE Jr, 2007. Cardiac troponins in the intensive care unit: common causes of increased levels and interpretation. Crit Care Med, 35(2):584-588.

[16]Fu XY, Kassim SY, Parks WC, et al., 2001. Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem, 276(44):41279-41287.

[17]Funayama A, Shishido T, Netsu S, et al., 2011. Serum pregnancy-associated plasma protein a in patients with heart failure. J Card Fail, 17(10):819-826.

[18]Glatz JFC, van Bilsen M, Paulussen RJA, et al., 1988. Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox. Biochim Biophys Acta, 961(1):148-152.

[19]Hanley JA, McNeil BJ, 1983. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology, 148(3):839-843.

[20]Huber W, Mayr U, Umgelter A, et al., 2018. Mandatory criteria for the application of variability-based parameters of fluid responsiveness: a prospective study in different groups of ICU patients. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(7):515-524.

[21]Janes H, Pepe MS, Gu W, 2008. Assessing the value of risk predictions by using risk stratification tables. Ann Intern Med, 149(10):751-760.

[22]Jardin F, Fourme T, Page B, et al., 1999. Persistent preload defect in severe sepsis despite fluid loading: a longitudinal echocardiographic study in patients with septic shock. Chest, 116(5):1354-1359.

[23]Jo YH, Kim K, Lee JH, et al., 2012. Heart-type fatty acid-binding protein as a prognostic factor in patients with severe sepsis and septic shock. Am J Emerg Med, 30(9):1749-1755.

[24]Kadowaki S, Watanabe T, Otaki Y, et al., 2017. Combined assessment of myocardial damage and electrical disturbance in chronic heart failure. World J Cardiol, 9(5):457-465.

[25]Kim JS, Kim M, Kim YJ, et al., 2019. Troponin testing for assessing sepsis-induced myocardial dysfunction in patients with septic shock. J Clin Med, 8(2):239.

[26]Klouche K, Pommet S, Amigues L, et al., 2014. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med, 29(4):229-237.

[27]Kolodziej AR, Abo-Aly M, Elsawalhy E, et al., 2019. Prognostic role of elevated myeloperoxidase in patients with acute coronary syndrome: a systemic review and meta-analysis. Mediat Inflamm, 2019:2872607.

[28]Kothari N, Keshari RS, Bogra J, et al., 2011. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care, 26(4):435.e1-435.e7.

[29]Levy MM, Fink MP, Marshall JC et al., 2003. 2001 SCCM/ ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med, 29:530-538.

[30]Mackinnon A, Mulligan R, 1998. Combining cognitive testing and informant report to increase accuracy in screening for dementia. Am J Psychiatry, 155(11):1529-1535.

[31]Mehta NJ, Khan IA, Gupta V, et al., 2004. Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic shock. Int J Cardiol, 95(1):13-17.

[32]Melenovsky V, Hwang SJ, Lin G, et al., 2014. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J, 35(48):3452-3462.

[33]Nakata T, Hashimoto A, Hase M, et al., 2003. Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome. Cardiology, 99(2):96-104.

[34]Ng LL, Pathik B, Loke IW, et al., 2006. Myeloperoxidase and C-reactive protein augment the specificity of B-type natriuretic peptide in community screening for systolic heart failure. Am Heart J, 152(1):94-101.

[35]O'Donoghue M, de Lemos JA, Morrow DA, et al., 2006. Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes. Circulation, 114(6):550-557.

[36]Papanikolaou J, Makris D, Mpaka M, et al., 2014. New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients. Crit Care, 18(3):R94.

[37]Park KC, Gaze DC, Collinson PO, et al., 2017. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res, 113(14):1708-1718.

[38]Parker MM, Shelhamer JH, Bacharach SL, et al., 1984. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med, 100(4):483-490.

[39]Pellitero S, Reverter JL, Pizarro E, et al., 2007. Pregnancy-associated plasma protein-A levels are related to glycemic control but not to lipid profile or hemostatic parameters in type 2 diabetes. Diabetes Care, 30(12):3083-3085.

[40]Pencina MJ, D'Agostino RB, D'Agostino RB Jr, et al., 2008. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med, 27(2):157-172.

[41]Pepe MS, Janes H, Longton G, et al., 2004. Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol, 159(9):882-890.

[42]Perner A, Cecconi M, Cronhjort M, et al., 2018. Expert statement for the management of hypovolemia in sepsis. Intensive Care Med, 44(6):791-798.

[43]Podrez EA, Febbraio M, Sheibani N, et al., 2000. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest, 105(8):1095-1108.

[44]Post F, Weilemann LS, Messow CM, et al., 2008. B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients. Crit Care Med, 36(11):3030-3037.

[45]Riedemann NC, Guo RF, Ward PA, 2003. Novel strategies for the treatment of sepsis. Nat Med, 9(5):517-524.

[46]Sato R, Nasu M, 2015. A review of sepsis-induced cardiomyopathy. J Intensive Care, 3:48.

[47]Schrijver IT, Kemperman H, Roest M, et al., 2017. Myeloperoxidase can differentiate between sepsis and non-infectious SIRS and predicts mortality in intensive care patients with SIRS. Intensive Care Med Exp, 5:43.

[48]Singer M, Deutschman CS, Seymour CW, et al., 2016. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 315(8):801-810.

[49]Wittfooth S, Tertti R, Lepäntalo M, et al., 2011. Studies on the effects of heparin products on pregnancy-associated plasma protein A. Clin Chim Acta, 412(3-4):376-381.

[50]Witthaut R, Busch C, Fraunberger P, et al., 2003. Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction. Intensive Care Med, 29(10):1696-1702.

[51]Yan GT, Lin J, Hao XH, et al., 2009. Heart-type fatty acid-binding protein is a useful marker for organ dysfunction and leptin alleviates sepsis-induced organ injuries by restraining its tissue levels. Eur J Pharmacol, 616(1-3):244-250.

[52]Yucel T, Memiş D, Karamanlioglu B, et al., 2008. The prognostic value of atrial and brain natriuretic peptides, troponin I and C-reactive protein in patients with sepsis. Exp Clin Cardiol, 13(4):183-188.

[53]Zhang ZC, Dai HW, Yu YH, et al., 2012. Usefulness of heart-type fatty acid-binding protein in patients with severe sepsis. J Crit Care, 27(4):415.e13-415.e18.

[54]Zhang ZC, Dai HW, Yu YH, et al., 2014. Elevated pregnancy-associated plasma protein A predicts myocardial dysfunction and death in severe sepsis. Ann Clin Biochem, 51(1):22-29.

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