Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

[1]  D. Atar,et al.  Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction , 2021, Annals of Internal Medicine.

[2]  P. Collinson,et al.  Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction , 2021, Circulation.

[3]  F. Apple,et al.  Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays , 2021, Clinical chemistry and laboratory medicine.

[4]  P. Ponikowski,et al.  Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure , 2021, European journal of heart failure.

[5]  A. Jaffe,et al.  99th Percentile Upper-Reference Limit of Cardiac Troponin and the Diagnosis of Acute Myocardial Infarction. , 2020, Clinical chemistry.

[6]  Deepak L. Bhatt,et al.  2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. , 2020, European heart journal.

[7]  Lu Lu,et al.  Statistical Intervals: A Guide for Practitioners and Researchers (2nd ed.) , 2020, Technometrics.

[8]  A. Tveit,et al.  Cardiac Troponin I and T Are Associated with Left Ventricular Function and Structure: Data from the Akershus Cardiac Examination 1950 Study. , 2020, Clinical chemistry.

[9]  L. Lam,et al.  Discrepancy between Cardiac Troponin Assays Due to Endogenous Antibodies. , 2020, Clinical chemistry.

[10]  C. Fischbacher,et al.  Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome , 2019, Journal of the American College of Cardiology.

[11]  Jia Wei,et al.  False decrease of high-sensitivity cardiac troponin T assay in pneumatic tube system samples. , 2019, Clinica chimica acta; international journal of clinical chemistry.

[12]  A. Peters,et al.  Application of High-Sensitivity Troponin in Suspected Myocardial Infarction. , 2019, The New England journal of medicine.

[13]  F. Apple,et al.  Clinical Features and Outcomes of Emergency Department Patients With High-Sensitivity Cardiac Troponin I Concentrations Within Sex-Specific Reference Intervals. , 2019, Circulation.

[14]  P. Collinson,et al.  How Does the Analytical Quality of the High-Sensitivity Cardiac Troponin T Assay Affect the ESC Rule Out Algorithm for NSTEMI? , 2019, Clinical chemistry.

[15]  A. Jaffe,et al.  Possible mechanisms behind cardiac troponin elevations , 2018, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[16]  Ò. Miró,et al.  Prospective Validation of the 0/1-h Algorithm for Early Diagnosis of Myocardial Infarction. , 2018, Journal of the American College of Cardiology.

[17]  P. Kavsak,et al.  Assessing matrix, interferences and comparability between the Abbott Diagnostics and the Beckman Coulter high-sensitivity cardiac troponin I assays , 2018, Clinical chemistry and laboratory medicine.

[18]  A. Lyon,et al.  Simulation Models of Misclassification Error for Single Thresholds of High-Sensitivity Cardiac Troponin I Due to Assay Bias and Imprecision. , 2017, Clinical chemistry.

[19]  L. Lind,et al.  The applied statistical approach highly influences the 99th percentile of cardiac troponin I. , 2016, Clinical biochemistry.

[20]  O. Holmen,et al.  Gender, High-Sensitivity Troponin I, and the Risk of Cardiovascular Events (from the Nord-Trøndelag Health Study). , 2016, The American journal of cardiology.

[21]  R. Body,et al.  Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T. , 2016, Annals of emergency medicine.

[22]  Harlan M Krumholz,et al.  Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association , 2016, Circulation.

[23]  J. Greenslade,et al.  Two-hour diagnostic algorithms for early assessment of patients with acute chest pain--Implications of lowering the cardiac troponin I cut-off to the 97.5th percentile. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[24]  P. H. Petersen,et al.  Weekly and 90-minute biological variations in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls. , 2014, Clinical chemistry.

[25]  M. V. van Dieijen-Visser,et al.  Circulating cardiac troponin T exhibits a diurnal rhythm. , 2014, Journal of the American College of Cardiology.

[26]  A. Jaffe,et al.  Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. , 2013, Clinical biochemistry.

[27]  K. Andrassy,et al.  Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'. , 2013, Kidney international.

[28]  A. Jaffe,et al.  Defining high-sensitivity cardiac troponin concentrations in the community. , 2013, Clinical chemistry.

[29]  M. Pfeffer,et al.  A sensitive cardiac troponin T assay in stable coronary artery disease. , 2009, The New England journal of medicine.

[30]  A. Jaffe,et al.  National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. , 2007, Clinical chemistry.

[31]  H. Kwon,et al.  The Influence of Hemolysis, Turbidity and Icterus on the Measurements of CK-MB, Troponin I and Myoglobin , 2003, Clinical chemistry and laboratory medicine.

[32]  A. Jaffe,et al.  It's time for a change to a troponin standard. , 2000, Circulation.

[33]  Michael S. Ewer,et al.  Cardiotoxicity of anticancer treatments , 2015, Nature Reviews Cardiology.

[34]  P. Collinson,et al.  Influence of population selection on the 99th percentile reference value for cardiac troponin assays. , 2012, Clinical chemistry.

[35]  B. Lewis,et al.  [The new universal definition of myocardial infarction]. , 2009, Harefuah.

[36]  M. Balabolkin,et al.  [Classification of diabetes mellitus]. , 1980, Terapevticheskii arkhiv.