Home Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
Article
Licensed
Unlicensed Requires Authentication

Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences

  • Ferruh Artunc EMAIL logo , Stefanie Haag , Björn Friedrich , Christian Mueller , Hans-Ulrich Häring and Andreas Peter
Published/Copyright: March 20, 2019
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 8

Abstract

Background

High sensitivity assays for the determination of cardiac troponin I (cTnI) are able to reliably measure cTnI far below the 99th percentile of healthy persons (hs-cTnI) and display sex-specific differences. There is uncertainty regarding the clinical utility of hs-cTnI in asymptomatic hemodialysis (HD) patients and if sex-specific differences also apply in this cohort.

Methods

In this multicenter study we measured hs-cTnI and sensitive cTnI (s-TnI) concentrations (both on Siemens Centaur) in 215 HD patients from a predialytic sample to determine the prevalence of elevated concentrations above the 99th percentile, the association with baseline characteristics, prognostic accuracy for death, and sex-specific differences.

Results

Hs-cTnI and s-cTnI concentrations were below the 99th percentile in 93% and 85% of patients with a median concentration of 12 ng/L (interquartile range 7–66) and 19 ng/L (12; 31, p < 0.0001). Hs-cTnI and s-cTnI concentrations were independently associated with age (p < 0.05) and ischemic cardiac disease (p < 0.05), but not with residual renal function. Both hs-cTnI and s-cTnI were predictors of death after median follow-up of 2.6 years with an AUC of 0.733 and 0.744, respectively (both p < 0.0001). Important sex-differences emerged for hs-cTnI, but not for s-cTnI: first, women had significantly lower hs-cTnI concentrations than men (p = 0.03); second, hs-cTnI had significantly higher prognostic accuracy for death in women than for men (AUC 0.824 vs. 0.674, p = 0.04).

Conclusions

The majority of HD patients have (h)s-cTnI concentrations below the 99th percentile. High normal values are predictive of death. Hs-cTnI allows to elucidate important sex-differences in HD patients with lower concentrations and higher prognostic accuracy in women.

Keywords: hemodialysis; high sensitivity; prognosis; sex-specific; troponin I
Corresponding author: Ferruh Artunc, MD, Corresponding author: Ferruh Artunc, MD, Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology and Nephrology, University Hospital of Tuebingen, Otfried-Mueller-Str. 10, 72076 Tuebingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tuebingen, Tuebingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany; and German Center for Diabetes Research (DZD), Tuebingen, Germany, Phone: +49-7071-2982711, Fax: +49-7071-2925215

Acknowledgments

We thank all study participants. Also, we gratefully acknowledge the technical support of Susanne Faix and Isolde Riedlinger.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Parts of the reagents for this study were provided free of charge by the manufacturer, Siemens Healthineers Eschborn, Germany. Professor Mueller received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the KTI, the Cardiovascular Research Foundation Basel, Abbott, Astra Zeneca, Biomerieux, Beckman Coulter, BRAHMS, Indorsia, Roche, Siemens, and Singulex, as well as a speaker/consulting honoraria or travel support from Abbott, Amgen, Bayer, BMS, Boehringer Ingelheim, BRAHMS, Cardiorentis, Daiichi Sankyo, Indorsia, Novartis, Roche, Sanofi, Siemens, and Singulex. Professor Peter has received a speaker honoraria and/or travel support Roche, Siemens, Abbott and Bioporto.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Collinson PO, Boa FG, Gaze DC. Measurement of cardiac troponins. Ann Clin Biochem 2001;38:423–49.10.1177/000456320103800501Search in Google Scholar

2. Adams 3rd JE. Clinical application of markers of cardiac injury: basic concepts and new considerations. Clin Chim Acta 1999;284:127–34.10.1016/S0009-8981(99)00074-1Search in Google Scholar

3. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237–69.10.1093/eurheartj/ehy462Search in Google Scholar

4. Garg P, Morris P, Fazlanie AL, Vijayan S, Dancso B, Dastidar AG, et al. Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin. Intern Emerg Med 2017;12:147–55.10.1007/s11739-017-1612-1Search in Google Scholar

5. Giannitsis E, Katus HA. Cardiac troponin level elevations not related to acute coronary syndromes. Nat Rev Cardiol 2013;10:623–34.10.1038/nrcardio.2013.129Search in Google Scholar

6. Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol 2002;40:2065–71.10.1016/S0735-1097(02)02608-6Search in Google Scholar

7. Artunc F, Haap M, Heyne N, Weyrich P, Wolf S. [Interpretation of elevated serum troponin levels in end stage renal disease – case 2/2010]. Dtsch Med Wochenschr 2010;135:240.10.1055/s-0030-1247609Search in Google Scholar PubMed

8. Katus HA, Haller C, Muller-Bardorff M, Scheffold T, RemppisA. Cardiac troponin T in end-stage renal disease patients undergoing chronic maintenance hemodialysis. Clin Chem 1995;41:1201–3.10.1093/clinchem/41.8.1201Search in Google Scholar

9. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002;106:2941–5.10.1161/01.CIR.0000041254.30637.34Search in Google Scholar

10. Artunc F, Mueller C, Breidthardt T, Twerenbold R, Peter A, ThamerC, et al. Sensitive troponins – which suits better for hemodialysis patients? Associated factors and prediction of mortality. PLoS One 2012;7:e47610.10.1371/journal.pone.0047610Search in Google Scholar PubMed PubMed Central

11. Stolear JC, Georges B, Shita A, Verbeelen D. The predictive value of cardiac troponin T measurements in subjects on regular haemodialysis. Nephrol Dial Transplant 1999;14:1961–7.10.1093/ndt/14.8.1961Search in Google Scholar PubMed

12. Khan NA, Hemmelgarn BR, Tonelli M, Thompson CR, LevinA. Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis.Circulation 2005;112:3088–96.10.1161/CIRCULATIONAHA.105.560128Search in Google Scholar PubMed

13. Michos ED, Wilson LM, Yeh H, Berger Z, Suarez-Cuervo C, Stacy SR, et al. Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: A systematic review and meta-analysis. Ann Intern Med 2014;161:491–501.10.7326/M14-0743Search in Google Scholar PubMed

14. Diris JH, Hackeng CM, Kooman JP, Pinto YM, Hermens WT, van Dieijen-Visser MP. Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients. Circulation 2004;109:23–5.10.1161/01.CIR.0000109483.45211.8FSearch in Google Scholar PubMed

15. Wang AY, Lai KN. Use of cardiac biomarkers in end-stage renal disease. J Am Soc Nephrol 2008;19:1643–52.10.1681/ASN.2008010012Search in Google Scholar PubMed

16. Kanderian AS, Francis GS. Cardiac troponins and chronic kidney disease. Kidney Int 2006;69:1112–4.10.1038/sj.ki.5000174Search in Google Scholar PubMed

17. Keller T, Wanner C, Krane V, Kraus D, Genser B, Scharnagl H, et al. Prognostic value of high-sensitivity versus conventional cardiac troponin T assays among patients with type 2 diabetes mellitus undergoing maintenance hemodialysis. Am J Kidney Dis 2018;71:822–30.10.1053/j.ajkd.2017.10.016Search in Google Scholar PubMed

18. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361:858–67.10.1056/NEJMoa0900428Search in Google Scholar PubMed

19. Jarolim P. Terminology of cardiac troponin assays and data censoring. Clin Chem Lab Med 2017;55:1672–4.10.1515/cclm-2017-0258Search in Google Scholar PubMed

20. Boeddinghaus J, Twerenbold R, Nestelberger T, Badertscher P, Wildi K, Puelacher C, et al. Clinical validation of a novel high-sensitivity cardiac troponin I assay for early diagnosis of acute myocardial infarction. Clin Chem 2018;64:1347–60.10.1373/clinchem.2018.286906Search in Google Scholar PubMed

21. Gore MO, Seliger SL, deFilippi CR, Nambi V, Christenson RH, Hashim IA, et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;63:1441–8.10.1016/j.jacc.2013.12.032Search in Google Scholar PubMed PubMed Central

22. Gunsolus I, Sandoval Y, Smith SW, Sexter A, Schulz K, Herzog CA, et al. Renal dysfunction influences the diagnostic and prognostic performance of high-sensitivity cardiac troponin I. J Am Soc Nephrol 2018;29:636–43.10.1681/ASN.2017030341Search in Google Scholar PubMed PubMed Central

23. Haag S, Friedrich B, Peter A, Haring HU, Heyne N, Artunc F. Systemic haemodynamics in haemodialysis: intradialytic changes and prognostic significance. Nephrol Dial Transplant 2018;33:1419–27.10.1093/ndt/gfy041Search in Google Scholar PubMed PubMed Central

24. Musetti V, Masotti S, Prontera C, Storti S, Ndreu R, Zucchelli Gian C, et al. Evaluation of the analytical performance of a new ADVIA immunoassay using the Centaur XPT platform system for the measurement of cardiac troponin I. Clin Chem Lab Med 2018;56:e229–31.10.1515/cclm-2018-0054Search in Google Scholar PubMed

25. Chamney PW, Wabel P, Moissl UM, Muller MJ, Bosy-Westphal A, Korth O, et al. A whole-body model to distinguish excess fluid from the hydration of major body tissues. Am J Clin Nutr 2007;85:80–9.10.1093/ajcn/85.1.80Search in Google Scholar PubMed

26. Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW,Bosy-Westphal A, et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas 2006;27:921–33.10.1088/0967-3334/27/9/012Search in Google Scholar PubMed

27. Schork A, Woern M, Kalbacher H, Voelter W, Nacken R, Bertog M, et al. Association of plasminuria with overhydration in patients with CKD. Clin J Am Soc Nephrol 2016;11:761–9.10.2215/CJN.12261115Search in Google Scholar PubMed PubMed Central

28. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45.10.2307/2531595Search in Google Scholar

29. Kimenai DM, Janssen E, Eggers KM, Lindahl B, den Ruijter HM, Bekers O, et al. Sex-specific versus overall clinical decision limits for cardiac troponin I and T for the diagnosis of acute myocardial infarction: a systematic review. Clin Chem 2018;64:1034–43.10.1373/clinchem.2018.286781Search in Google Scholar PubMed

30. Collinson PO, Heung YM, Gaze D, Boa F, Senior R, Christenson R, et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012;58:219–25.10.1373/clinchem.2011.171082Search in Google Scholar PubMed

31. Welsh P, Preiss D, Shah ASV, McAllister D, Briggs A, Boachie C, et al. Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Clin Chem 2018;64:1607–16.10.1373/clinchem.2018.292086Search in Google Scholar PubMed PubMed Central

32. Clerico A, Zaninotto M, Ripoli A, Masotti S, Prontera C, Passino C, et al. The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications. Clin Chem Lab Med 2017;55:1634–51.10.1515/cclm-2016-0933Search in Google Scholar PubMed

33. Artunc F, Nowak A, Muller C, Peter A, Heyne N, Haring HU, et al. Mortality prediction using modern peptide biomarkers in hemodialysis patients – a comparative analysis. Kidney Blood Press Res 2014;39:563–72.10.1159/000368468Search in Google Scholar PubMed

34. Artunc F, Mueller C, Breidthardt T, Twerenbold R, Rettig I, Usta E, et al. Comparison of the diagnostic performance of three natriuretic peptides in hemodialysis patients: which is the appropriate biomarker? Kidney Blood Press Res 2012;36: 172–81.10.1159/000343406Search in Google Scholar PubMed

Received: 2018-11-01
Accepted: 2019-02-14
Published Online: 2019-03-20
Published in Print: 2019-07-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper
  4. Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler
  5. Reviews
  6. Blood contamination in salivary diagnostics: current methods and their limitations
  7. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment
  8. Genetics and Molecular Diagnostics
  9. Measuring the chronology of the translational process of molecular genetic discoveries
  10. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements
  11. General Clinical Chemistry and Laboratory Medicine
  12. Post-translational modification-derived products are associated with frailty status in elderly subjects
  13. Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease
  14. Estimated urinary osmolality based on combined urinalysis parameters: a critical evaluation
  15. Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer
  16. Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma
  17. Human chorionic gonadotropin suspected heterophile interference investigations in immunoassays: a recommended approach
  18. Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification
  19. Diagnostic accuracy of a fully automated multiplex celiac disease antibody panel for serum and plasma
  20. Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status
  21. Hematology and Coagulation
  22. The association between activated protein C ratio and Factor V Leiden are gender-dependent
  23. Reference Values and Biological Variations
  24. Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?
  25. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases
  26. Cancer Diagnostics
  27. Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
  28. Cardiovascular Diseases
  29. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
  30. Infectious Diseases
  31. Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring
  32. Letters to the Editor
  33. Vitamin B12 and folate levels in a healthy population: establishing reference intervals
  34. Reference values of a new serum folate assay traceable to the WHO International Standard
  35. Serum protein electrophoresis and complement deficiencies: a veteran but very versatile test in clinical laboratories
  36. Introduction of a novel ELISA assay for serum AMH determination
  37. Bone alkaline phosphatase on the IDS-iSYS automated analyser; cross-reactivity with intestinal ALP
  38. Evaluation of the MULTISURE HIV Rapid Test in a Korean population with low human immunodeficiency virus prevalence
  39. Vancomycin immunoassay: does the Advia Centaur XPT underestimate the exposure of patients? A method comparison study
  40. Hb Hunan and Hb Hengyang: Two unexpected discoveries during HbA1c measurements
  41. Analytical performance of a CE-marked immunoassay to quantify phosphorylated neurofilament heavy chains
  42. Implementation of an automated method for direct quantification of urinary ammonium
  43. Congress Abstracts
  44. Proceedings of ACBI 2018 41ST Annual Conference Association of Clinical Biochemists in Ireland
https://doi.org/10.1515/cclm-2018-1176
Keywords for this article
hemodialysis; high sensitivity; prognosis; sex-specific; troponin I

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper
  4. Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler
  5. Reviews
  6. Blood contamination in salivary diagnostics: current methods and their limitations
  7. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment
  8. Genetics and Molecular Diagnostics
  9. Measuring the chronology of the translational process of molecular genetic discoveries
  10. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements
  11. General Clinical Chemistry and Laboratory Medicine
  12. Post-translational modification-derived products are associated with frailty status in elderly subjects
  13. Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease
  14. Estimated urinary osmolality based on combined urinalysis parameters: a critical evaluation
  15. Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer
  16. Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma
  17. Human chorionic gonadotropin suspected heterophile interference investigations in immunoassays: a recommended approach
  18. Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification
  19. Diagnostic accuracy of a fully automated multiplex celiac disease antibody panel for serum and plasma
  20. Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status
  21. Hematology and Coagulation
  22. The association between activated protein C ratio and Factor V Leiden are gender-dependent
  23. Reference Values and Biological Variations
  24. Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?
  25. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases
  26. Cancer Diagnostics
  27. Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
  28. Cardiovascular Diseases
  29. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
  30. Infectious Diseases
  31. Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring
  32. Letters to the Editor
  33. Vitamin B12 and folate levels in a healthy population: establishing reference intervals
  34. Reference values of a new serum folate assay traceable to the WHO International Standard
  35. Serum protein electrophoresis and complement deficiencies: a veteran but very versatile test in clinical laboratories
  36. Introduction of a novel ELISA assay for serum AMH determination
  37. Bone alkaline phosphatase on the IDS-iSYS automated analyser; cross-reactivity with intestinal ALP
  38. Evaluation of the MULTISURE HIV Rapid Test in a Korean population with low human immunodeficiency virus prevalence
  39. Vancomycin immunoassay: does the Advia Centaur XPT underestimate the exposure of patients? A method comparison study
  40. Hb Hunan and Hb Hengyang: Two unexpected discoveries during HbA1c measurements
  41. Analytical performance of a CE-marked immunoassay to quantify phosphorylated neurofilament heavy chains
  42. Implementation of an automated method for direct quantification of urinary ammonium
  43. Congress Abstracts
  44. Proceedings of ACBI 2018 41ST Annual Conference Association of Clinical Biochemists in Ireland
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 17.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2018-1176/html
Scroll to top button