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Using logistic regression models to investigate the effects of high-sensitivity cardiac troponin T confounders on ruling in acute myocardial infarction

  • Li Liu EMAIL logo , Xueya Cai , Tanzy Love , Matthew Corsetti , Andrew M. Mathias , Andrew Worster , Jinhui Ma and Peter A. Kavsak
Published/Copyright: January 26, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 7

Abstract

Objectives

Confounding factors, including sex, age, and renal dysfunction, affect high-sensitivity cardiac troponin T (hs-cTnT) concentrations and the acute myocardial infarction (AMI) diagnosis. This study assessed the effects of these confounders through logistic regression models and evaluated the diagnostic performance of an optimized, integrated prediction model.

Methods

This retrospective study included a primary derivation cohort of 18,022 emergency department (ED) patients at a US medical center and a validation cohort of 890 ED patients at a Canadian medical center. Hs-cTnT was measured with 0/3 h sampling. The primary outcome was index AMI diagnosis. Logistic regression models were optimized to predict AMI using delta hs-cTnT and its confounders as covariates. The diagnostic performance of model cutoffs was compared to that of the hs-cTnT delta thresholds. Serial logistic regressions were carried out to evaluate the relationship between covariates.

Results

The area under the curve of the best-fitted model was 0.95. The model achieved a 90.0% diagnostic accuracy in the validation cohort. The optimal model cutoff yielded comparable performance (90.5% accuracy) to the optimal sex-specific delta thresholds (90.3% accuracy), with 95.8% agreement between the two diagnostic methods. Serial logistic regressions revealed that delta hs-cTnT played a more predominant role in AMI prediction than its confounders, among which sex is more predictive of AMI (total effect coefficient 1.04) than age (total effect coefficient 0.05) and eGFR (total effect coefficient −0.008).

Conclusions

The integrated prediction model incorporating confounding factors does not outperform hs-cTnT delta thresholds. Sex-specific hs-cTnT delta thresholds remain to provide the highest diagnostic accuracy.

Keywords: acute coronary syndrome; AMI; cardiac troponin; clinical chemistry; confounding factors; high-sensitivity cardiac troponin assay
Corresponding author: Li Liu, MD, PhD, Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, GRB-554B, Boston, MA 02114, USA; Harvard Medical School, Boston, MA, USA; and Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA, Phone: 617-726-9653, Fax: 617-726-7474, E-mail:

  1. Research funding: This work was partially supported by the United States National Institute of Environmental Health Sciences at the National Institutes of Health (Grant T32ES007271). The study sponsors had no role in the study design; in the collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the article for publication.

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

  3. Competing interests: Peter Kavsak has received grants and provision of study materials from Roche Diagnostics, Abbott Laboratories, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, and Siemens Healthcare Diagnostics. He has received consulting fees or honoraria from Abbott Laboratories, Beckman Coulter, Quidel, Roche Diangostics, Siemens Healthcare Diagnostics, and Thermo Fisher Scientific. He has received support for attending meetings from Randox Laboratories. Peter Kavsak and Andrew Worster have a pending patent application filed by McMaster University as inventors in the acute cardiovascular biomarker field. Andrew Worster has received research grant from the Canadian Institute of Health Research. Xueya Cai has received research grant from the National Institutes of Health. No other financial relationships were declared.

  4. Informed consent: Not applicable.

  5. Ethical approval: This retrospective study consisted of a primary cohort approved by the University of Rochester Institutional Review Board and an external validation cohort with previous approval by the Hamilton Integrated Research Ethics Board.

  6. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-10-06
Accepted: 2023-01-16
Published Online: 2023-01-26
Published in Print: 2023-06-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-1004
Keywords for this article
acute coronary syndrome; AMI; cardiac troponin; clinical chemistry; confounding factors; high-sensitivity cardiac troponin assay

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  1. Frontmatter
  2. Editorial
  3. ChatGPT: Angel or Demond? Critical thinking is still needed
  4. Mini Review
  5. Diagnostic accuracy of Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosing acute SARS-CoV-2 infection: a pooled analysis
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  8. Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs
  9. EFLM Papers
  10. Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI)
  11. Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP
  12. Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey
  13. Guidelines and Recommendations
  14. Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance
  15. General Clinical Chemistry and Laboratory Medicine
  16. Pre-analytical long-term stability of neopterin and neurofilament light in stored cerebrospinal fluid samples
  17. Development of a candidate reference measurement procedure by ID-LC-MS/MS for total tau protein measurement in cerebrospinal fluid (CSF)
  18. Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
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