The Relationship between Thioredoxin-2, Systemic Immune-inflammatory Index, and Short-term Adverse Cardiovascular Events in Septic Cardiomyopathy
-
Yafei Zhang
,
Dahe Han
,
Chun Yang
,
Yali Chao
,
Qing Xiao
,
Chenliang Sun
,
Yi Guo
Abstract
To explore the relationship between thioredoxins (Trx) -2, systemic-immune inflammatory index (SII), and short-term major adverse cardiac events (MACE) in septic cardiomyopathy (SCM).
A retrospective study was conducted on 98 SCM patients admitted to Affiliated Jinling Hospital, Medical School of Nanjing University Emergency Intensive Care Unit (EICU) from July 2022 to June 2024. Patients underwent routine blood tests and data assessment upon admission. Based on the occurrence of MACE by day 28, patients were divided into the MACE group and the non-MACE (N-MACE) group. Clinical data were collected, and logistic regression, along with restricted cubic spline models, analyzed the relationships between SII, Trx-2, and MACE risk in SCM patients.
Among the 98 SCM patients included, there were 35 (35.71%) in the MACE group and 63 (64.29%) in the N-MACE group. Logistic regression analysis showed that elevated SII and serum Trx-2 levels correlated with an increased risk of MACE within 28 days post-admission for SCM patients. Restricted cubic spline analysis revealed a linear dose-response relationship between both SII and Trx-2 levels with short-term MACE risk in SCM. The ROC curve showed AUC values of 0.869 for LVEF, 0.881 for SII, while combining SII + Trx-2 yielded 0.926 (95% CI: 0.862-0.989), with specificity at 83.98 % and sensitivity at 98.80%.
The abnormal increase of serum SII and Trx-2 levels in SCM patients is related to the occurrence of MACE within 28 days after admission. The risk of MACE increases with the increase of serum SII and Trx-2 levels.
1. Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, et al. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022;9(1):56.
2. Srzić I, Nesek Adam V, Tunjić Pejak D. SEPSIS DEFINITION: WHAT'S NEW IN THE TREATMENT GUIDELINES. Acta Clin Croat. 2022;61(Suppl 1):67-72.
3. Jacobi J. The pathophysiology of sepsis - 2021 update: Part 2, organ dysfunction and assessment. Am J Health Syst Pharm. 2022;79(6):424-36.
4. Narváez I, Canabal A, Martín C, Sánchez M, Moron A, Alcalá J, et al. Incidence and evolution of sepsis-induced cardiomyopathy in a cohort of patients with sepsis and septic shock. Med Intensiva (Engl Ed). 2018;42(5):283-291.
5. Jayaprakash N, Gajic O, Frank RD, Smischney N. Elevated modified shock index in early sepsis is associated with myocardial dysfunction and mortality. J Crit Care. 2018;43(8):30-35.
6. Boissier F, Aissaoui N. Septic cardiomyopathy: Diagnosis and management. J Intensive Med. 2021;2(1):8-16.
7. Carbone F, Liberale L, Preda A, Schindler TH, Montecucco F. Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting. Cells. 2022;11(18):2833.
8. Yang B, Lin Y, Huang Y, Shen YQ, Chen Q. Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases. Redox Biol. 2024;70(5):103032.
9. Kundumani-Sridharan V, Subramani J, Owens C, Das KC. Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy. Arterioscler Thromb Vasc Biol. 2021;41(8):2293-14.
10. Wei ZX, Cai XX, Fei YD, Wang Q, Hu XL, Li C, et al. Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling. Cell Mol Life Sci. 2024;81(1):88.
11. Chen Z, Feng Y, Zhang RB, Li X, Xu JB. Effect of grelin on TRX expression in chronic heart failure tissue: A protocol of systematic review and meta-analysis. Medicine (Baltimore). 2020;99(21):e20294.
12. Wang X, Xing Y, Tang Z, Tang Y, Shen J, Zhang F. Thioredoxin-2 impacts the inflammatory response via suppression of NF-κB and MAPK signaling in sepsis shock. Biochem Biophys Res Commun. 2020;524(4):876-82.
13. Xia Y, Xia C, Wu L, Li Z, Li H, Zhang J. Systemic Immune Inflammation Index (SII), System Inflammation Response Index (SIRI) and Risk of All-Cause Mortality and Cardiovascular Mortality: A 20-Year Follow-Up Cohort Study of 42,875 US Adults. J Clin Med. 2023;12(3):1128.
14. Ding P, Guo H, Sun C, Yang P, Kim NH, Tian Y, et al. Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study. BMC Gastroenterol. 2022;22(1):121.
15. Sun J, Qi Y, Wang W, Meng P, Han C, Chen B. Systemic Immune-Inflammation Index (SII) as a Predictor of Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study. Med Sci Monit. 2024;30:e943414.
16. Jiang D, Bian T, Shen Y, Huang Z. Association between admission systemic immune-inflammation index and mortality in critically ill patients with sepsis: a retrospective cohort study based on MIMIC-IV database. Clin Exp Med. 2023;23(7):3641-50.
17. Liu C, Wu X, Deng R, Xu X, Chen C, Wu L, et al. Systemic immune-inflammation index combined with quick sequential organ failure assessment score for predicting mortality in sepsis patients. Heliyon. 2023;9(9):e19526.
18. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247.
19. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, Damske BA, Parrillo JE. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med. 1984;100(4):483-90.
20. Ye C, Yuan L, Wu K, Shen B, Zhu C. Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study. BMC Pulm Med. 2023;23(1):295.
21. Zhang S, Wei Y, Liu J, Zhuang Y. MiR-940 Serves as a Diagnostic Biomarker in Patients with Sepsis and Regulates Sepsis-Induced Inflammation and Myocardial Dysfunction. J Inflamm Res. 2021;14(4):4567-4574.
22. Zimmerman JE, Kramer AA. Outcome prediction in critical care: the Acute Physiology and Chronic Health Evaluation models. Curr Opin Crit Care. 2008;14(5):491-7.
23. Balamuth F, Scott HF, Weiss SL, Webb M, Chamberlain JM, Bajaj L, et al. Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department. JAMA Pediatr. 2022;176(7):672-8.
24. Lin YM, Lee MC, Toh HS, Chang WT, Chen SY, Kuo FH, et al. Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis. Ann Intensive Care. 2022;12(1):112.
25. Yang J, Ran T, Lin X, Xu J, Zhou S, Chen C, et al. Association between preoperative systemic immune inflammation index and postoperative sepsis in patients with intestinal obstruction: A retrospective observational cohort study. Immun Inflamm Dis. 2024;12(2):e1187.
26. Pricop M, Ancusa O, Talpos S, Urechescu H, Bumbu BA. The Predictive Value of Systemic Immune-Inflammation Index and Symptom Severity Score for Sepsis and Systemic Inflammatory Response Syndrome in Odontogenic Infections. J Pers Med. 2022;12(12):2026.
27. Ni J, Wang H, Li Y, Shu Y, Liu Y. Neutrophil to lymphocyte ratio (NLR) as a prognostic marker for in-hospital mortality of patients with sepsis: A secondary analysis based on a single-center, retrospective, cohort study. Medicine (Baltimore). 2019;98(46):e18029.
28. Su M, Chen C, Li S, Li M, Zeng Z, Zhang Y, et al. Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nat Cardiovasc Res. 2022;1(8):732-47.
29. Russell NJ, Stöhr W, Plakkal N, Cook A, Berkley JA, Adhisivam B, et al. Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS). PLoS Med. 2023;20(6):e1004179.
30. Mangalesh S, Dudani S, Malik A. The systemic immune-inflammation index in predicting sepsis mortality. Postgrad Med. 2023;135(4):345-51.
31. Li YY, Xiang Y, Zhang S, Wang Y, Yang J, Liu W, et al. Thioredoxin-2 protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy and apoptosis in H9c2 cardiomyocytes. Am J Transl Res. 2017;9(3):1471-82.
32. Matsuo Y. Introducing Thioredoxin-Related Transmembrane Proteins: Emerging Roles of Human TMX and Clinical Implications. Antioxid Redox Signal. 2022;36(13-15):984-1000.
33. Lu H, Li S, Zhong X, Huang S, Jiao X, He G, et al. Immediate outcome prognostic value of plasma factors in patients with acute ischemic stroke after intravenous thrombolytic treatment. BMC Neurol. 2022;22(1):359.
34. Zhang W, Chen H, Xu Z, Zhang X, Tan X, He N, et al. Liensinine pretreatment reduces inflammation, oxidative stress, apoptosis, and autophagy to alleviate sepsis acute kidney injury. Int Immunopharmacol. 2023;122(8):110563.
35. Liu AB, Li SJ, Yu YY, Zhang JF, Ma L. Current insight on the mechanisms of programmed cell death in sepsis-induced myocardial dysfunction. Front Cell Dev Biol. 2023;11(9):1309719.
36. Qin Z, Shen S, Qu K, Nie Y, Zhang H. Mild hypothermia in rat with acute myocardial ischaemia-reperfusion injury complicating severe sepsis. J Cell Mol Med. 2021;25(13):6448–54.
37. Levy B, Girerd N, Amour J, Besnier E, Nesseler N, Helms J, et al. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial. JAMA. 2022;327(5):442-53.
2. Srzić I, Nesek Adam V, Tunjić Pejak D. SEPSIS DEFINITION: WHAT'S NEW IN THE TREATMENT GUIDELINES. Acta Clin Croat. 2022;61(Suppl 1):67-72.
3. Jacobi J. The pathophysiology of sepsis - 2021 update: Part 2, organ dysfunction and assessment. Am J Health Syst Pharm. 2022;79(6):424-36.
4. Narváez I, Canabal A, Martín C, Sánchez M, Moron A, Alcalá J, et al. Incidence and evolution of sepsis-induced cardiomyopathy in a cohort of patients with sepsis and septic shock. Med Intensiva (Engl Ed). 2018;42(5):283-291.
5. Jayaprakash N, Gajic O, Frank RD, Smischney N. Elevated modified shock index in early sepsis is associated with myocardial dysfunction and mortality. J Crit Care. 2018;43(8):30-35.
6. Boissier F, Aissaoui N. Septic cardiomyopathy: Diagnosis and management. J Intensive Med. 2021;2(1):8-16.
7. Carbone F, Liberale L, Preda A, Schindler TH, Montecucco F. Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting. Cells. 2022;11(18):2833.
8. Yang B, Lin Y, Huang Y, Shen YQ, Chen Q. Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases. Redox Biol. 2024;70(5):103032.
9. Kundumani-Sridharan V, Subramani J, Owens C, Das KC. Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy. Arterioscler Thromb Vasc Biol. 2021;41(8):2293-14.
10. Wei ZX, Cai XX, Fei YD, Wang Q, Hu XL, Li C, et al. Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling. Cell Mol Life Sci. 2024;81(1):88.
11. Chen Z, Feng Y, Zhang RB, Li X, Xu JB. Effect of grelin on TRX expression in chronic heart failure tissue: A protocol of systematic review and meta-analysis. Medicine (Baltimore). 2020;99(21):e20294.
12. Wang X, Xing Y, Tang Z, Tang Y, Shen J, Zhang F. Thioredoxin-2 impacts the inflammatory response via suppression of NF-κB and MAPK signaling in sepsis shock. Biochem Biophys Res Commun. 2020;524(4):876-82.
13. Xia Y, Xia C, Wu L, Li Z, Li H, Zhang J. Systemic Immune Inflammation Index (SII), System Inflammation Response Index (SIRI) and Risk of All-Cause Mortality and Cardiovascular Mortality: A 20-Year Follow-Up Cohort Study of 42,875 US Adults. J Clin Med. 2023;12(3):1128.
14. Ding P, Guo H, Sun C, Yang P, Kim NH, Tian Y, et al. Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study. BMC Gastroenterol. 2022;22(1):121.
15. Sun J, Qi Y, Wang W, Meng P, Han C, Chen B. Systemic Immune-Inflammation Index (SII) as a Predictor of Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study. Med Sci Monit. 2024;30:e943414.
16. Jiang D, Bian T, Shen Y, Huang Z. Association between admission systemic immune-inflammation index and mortality in critically ill patients with sepsis: a retrospective cohort study based on MIMIC-IV database. Clin Exp Med. 2023;23(7):3641-50.
17. Liu C, Wu X, Deng R, Xu X, Chen C, Wu L, et al. Systemic immune-inflammation index combined with quick sequential organ failure assessment score for predicting mortality in sepsis patients. Heliyon. 2023;9(9):e19526.
18. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247.
19. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, Damske BA, Parrillo JE. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med. 1984;100(4):483-90.
20. Ye C, Yuan L, Wu K, Shen B, Zhu C. Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study. BMC Pulm Med. 2023;23(1):295.
21. Zhang S, Wei Y, Liu J, Zhuang Y. MiR-940 Serves as a Diagnostic Biomarker in Patients with Sepsis and Regulates Sepsis-Induced Inflammation and Myocardial Dysfunction. J Inflamm Res. 2021;14(4):4567-4574.
22. Zimmerman JE, Kramer AA. Outcome prediction in critical care: the Acute Physiology and Chronic Health Evaluation models. Curr Opin Crit Care. 2008;14(5):491-7.
23. Balamuth F, Scott HF, Weiss SL, Webb M, Chamberlain JM, Bajaj L, et al. Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department. JAMA Pediatr. 2022;176(7):672-8.
24. Lin YM, Lee MC, Toh HS, Chang WT, Chen SY, Kuo FH, et al. Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis. Ann Intensive Care. 2022;12(1):112.
25. Yang J, Ran T, Lin X, Xu J, Zhou S, Chen C, et al. Association between preoperative systemic immune inflammation index and postoperative sepsis in patients with intestinal obstruction: A retrospective observational cohort study. Immun Inflamm Dis. 2024;12(2):e1187.
26. Pricop M, Ancusa O, Talpos S, Urechescu H, Bumbu BA. The Predictive Value of Systemic Immune-Inflammation Index and Symptom Severity Score for Sepsis and Systemic Inflammatory Response Syndrome in Odontogenic Infections. J Pers Med. 2022;12(12):2026.
27. Ni J, Wang H, Li Y, Shu Y, Liu Y. Neutrophil to lymphocyte ratio (NLR) as a prognostic marker for in-hospital mortality of patients with sepsis: A secondary analysis based on a single-center, retrospective, cohort study. Medicine (Baltimore). 2019;98(46):e18029.
28. Su M, Chen C, Li S, Li M, Zeng Z, Zhang Y, et al. Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nat Cardiovasc Res. 2022;1(8):732-47.
29. Russell NJ, Stöhr W, Plakkal N, Cook A, Berkley JA, Adhisivam B, et al. Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS). PLoS Med. 2023;20(6):e1004179.
30. Mangalesh S, Dudani S, Malik A. The systemic immune-inflammation index in predicting sepsis mortality. Postgrad Med. 2023;135(4):345-51.
31. Li YY, Xiang Y, Zhang S, Wang Y, Yang J, Liu W, et al. Thioredoxin-2 protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy and apoptosis in H9c2 cardiomyocytes. Am J Transl Res. 2017;9(3):1471-82.
32. Matsuo Y. Introducing Thioredoxin-Related Transmembrane Proteins: Emerging Roles of Human TMX and Clinical Implications. Antioxid Redox Signal. 2022;36(13-15):984-1000.
33. Lu H, Li S, Zhong X, Huang S, Jiao X, He G, et al. Immediate outcome prognostic value of plasma factors in patients with acute ischemic stroke after intravenous thrombolytic treatment. BMC Neurol. 2022;22(1):359.
34. Zhang W, Chen H, Xu Z, Zhang X, Tan X, He N, et al. Liensinine pretreatment reduces inflammation, oxidative stress, apoptosis, and autophagy to alleviate sepsis acute kidney injury. Int Immunopharmacol. 2023;122(8):110563.
35. Liu AB, Li SJ, Yu YY, Zhang JF, Ma L. Current insight on the mechanisms of programmed cell death in sepsis-induced myocardial dysfunction. Front Cell Dev Biol. 2023;11(9):1309719.
36. Qin Z, Shen S, Qu K, Nie Y, Zhang H. Mild hypothermia in rat with acute myocardial ischaemia-reperfusion injury complicating severe sepsis. J Cell Mol Med. 2021;25(13):6448–54.
37. Levy B, Girerd N, Amour J, Besnier E, Nesseler N, Helms J, et al. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial. JAMA. 2022;327(5):442-53.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Cardiovascular diseases Cardiomyopathy Neutrophils Septic Thioredoxins | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Zhang Y, Han D, Yang C, Chao Y, Xiao Q, Sun C, Guo Y. The Relationship between Thioredoxin-2, Systemic Immune-inflammatory Index, and Short-term Adverse Cardiovascular Events in Septic Cardiomyopathy. Iran J Allergy Asthma Immunol. 2025;:1-12.
