Troponin testing: Analytical aspects
- Allan S Jaffe, MD
Allan S Jaffe, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Mayo Medical School
- David A Morrow, MD, MPH
David A Morrow, MD, MPH
- Professor of Medicine
- Harvard Medical School
- Section Editor
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
Cardiac injury occurs when there is disruption of normal cardiac myocyte membrane integrity. This results in the loss into the extracellular space (including blood) of intracellular constituents, including detectable levels of a variety of biologically active cytosolic enzymes and structural proteins, referred to as biomarkers, such as troponin, creatine kinase, myoglobin, heart-type fatty acid binding protein, and lactate dehydrogenase. Injury is usually considered irreversible (cell death), but definitive proof that cell death is always the cause when troponin is released, without possible contributions from reversible other mechanisms, is not available. (See "Troponin testing: Clinical use", section on 'Possible acute myocardial injury'.)
When a sufficient number of myocytes have died (myocyte necrosis), elevations of troponin occur. If this occurs over a short period, acute clinical disease may be apparent. If over a longer period, more chronic processes may be responsible. The causes of cardiac injury are numerous. Ischemia, consequent to an imbalance between the supply and demand of oxygen (and nutrients), is one common cause. Because earlier biomarkers of cardiac injury were much less sensitive and thus when elevated were more likely to reflect marked insults such as ischemia, some clinicians consider any elevation of a biomarker of cardiac injury as indicative of ischemic heart disease. However, this assumption has never been correct, and is even less so now that more sensitive markers such as troponin are in clinical use. Other causes of myocardial injury are included in a table (table 1).
The biochemical characteristics and utility of troponins for the diagnosis of cardiac injury, and acute myocardial infarction in particular, will be reviewed here. Other relevant topics include:
●(See "Troponin testing: Clinical use".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Adams JE 3rd, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 1990s? Circulation 1993; 88:750.
- Katus HA, Remppis A, Scheffold T, et al. Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. Am J Cardiol 1991; 67:1360.
- Adams JE 3rd, Schechtman KB, Landt Y, et al. Comparable detection of acute myocardial infarction by creatine kinase MB isoenzyme and cardiac troponin I. Clin Chem 1994; 40:1291.
- Adams JE 3rd, Bodor GS, Dávila-Román VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation 1993; 88:101.
- Bodor GS, Porterfield D, Voss EM, et al. Cardiac troponin-I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue. Clin Chem 1995; 41:1710.
- Jaffe AS, Vasile VC, Milone M, et al. Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol 2011; 58:1819.
- Rittoo D, Jones A, Lecky B, Neithercut D. Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: implications for the diagnosis of myocardial infarction. J Am Coll Cardiol 2014; 63:2411.
- Wens SC, Schaaf GJ, Michels M, et al. Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease. Circ Cardiovasc Genet 2016; 9:6.
- Wu AH, Fukushima N, Puskas R, et al. Development and preliminary clinical validation of a high sensitivity assay for cardiac troponin using a capillary flow (single molecule) fluorescence detector. Clin Chem 2006; 52:2157.
- Kavsak PA, MacRae AR, Yerna MJ, Jaffe AS. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem 2009; 55:573.
- Wilson SR, Sabatine MS, Braunwald E, et al. Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial. Am Heart J 2009; 158:386.
- Venge P, Johnston N, Lindahl B, James S. Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia. J Am Coll Cardiol 2009; 54:1165.
- Giannitsis E, Kurz K, Hallermayer K, et al. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010; 56:254.
- Latini R, Masson S, Anand IS, et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 2007; 116:1242.
- Januzzi JL Jr, Bamberg F, Lee H, et al. High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation 2010; 121:1227.
- Diamond GA, Kaul S. How would the Reverend Bayes interpret high-sensitivity troponin? Circulation 2010; 121:1172.
- Korley FK, Jaffe AS. Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol 2013; 61:1753.
- Apple FS. A new season for cardiac troponin assays: it's time to keep a scorecard. Clin Chem 2009; 55:1303.
- Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012; 58:1574.
- Aw TC, van Wijk XM, Wu AH, Jaffe AS. Release of cardiac troponin using a high sensitivity assay after exercise: Type 2 acute myocardial infarction? Clin Chim Acta 2015; 446:6.
- White HD. Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis? J Am Coll Cardiol 2011; 57:2406.
- Panteghini M, Pagani F, Yeo KT, et al. Evaluation of imprecision for cardiac troponin assays at low-range concentrations. Clin Chem 2004; 50:327.
- Apple FS, Quist HE, Doyle PJ, et al. Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations. Clin Chem 2003; 49:1331.
- Ricchiuti V, Voss EM, Ney A, et al. Cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second generation cardiac troponin T assay by Boehringer Mannheim. Clin Chem 1998; 44:1919.
- Shi Q, Ling M, Zhang X, et al. Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays. Clin Chem 1999; 45:1018.
- Labugger R, Organ L, Collier C, et al. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. Circulation 2000; 102:1221.
- Heeschen C, Goldmann BU, Langenbrink L, et al. Evaluation of a rapid whole blood ELISA for quantification of troponin I in patients with acute chest pain. Clin Chem 1999; 45:1789.
- Katrukha AG, Bereznikova AV, Esakova TV, et al. Troponin I is released in bloodstream of patients with acute myocardial infarction not in free form but as complex. Clin Chem 1997; 43:1379.
- Wu AH, Feng YJ, Moore R, et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization. Clin Chem 1998; 44:1198.
- Jaffe AS, Ravkilde J, Roberts R, et al. It's time for a change to a troponin standard. Circulation 2000; 102:1216.
- Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007; 28:2525.
- Schulz O, Kirpal K, Stein J, et al. Importance of low concentrations of cardiac troponins. Clin Chem 2006; 52:1614.
- Kavsak PA, Wang X, Ko DT, et al. Short- and long-term risk stratification using a next-generation, high-sensitivity research cardiac troponin I (hs-cTnI) assay in an emergency department chest pain population. Clin Chem 2009; 55:1809.
- Derdeyn CP. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009; 361:97; author reply 98.
- de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 2010; 304:2503.
- deFilippi CR, de Lemos JA, Christenson RH, et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA 2010; 304:2494.
- Frankenstein L, Wu AH, Hallermayer K, et al. Biological variation and reference change value of high-sensitivity troponin T in healthy individuals during short and intermediate follow-up periods. Clin Chem 2011; 57:1068.
- Collinson PO, Heung YM, Gaze D, et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012; 58:219.
- McKie PM, Heublein DM, Scott CG, et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013; 59:1099.
- Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009; 361:858.
- Keller T, Zeller T, Peetz D, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009; 361:868.
- Jaffe AS, Apple FS. High-sensitivity cardiac troponin: hype, help, and reality. Clin Chem 2010; 56:342.
- Mills NL, Churchhouse AM, Lee KK, et al. Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA 2011; 305:1210.
- Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012; 60:1581.
- Jaffe AS, Apple FS, Morrow DA, et al. Being rational about (im)precision: a statement from the Biochemistry Subcommittee of the Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the definition of myocardial infarction. Clin Chem 2010; 56:941.
- Wu AH, Jaffe AS. The clinical need for high-sensitivity cardiac troponin assays for acute coronary syndromes and the role for serial testing. Am Heart J 2008; 155:208.
- Bais R. The effect of sample hemolysis on cardiac troponin I and T assays. Clin Chem 2010; 56:1357.
- Kaur S. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. Ann Clin Biochem 2015; 52:622.
- Macrae AR, Kavsak PA, Lustig V, et al. Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem 2006; 52:812.
- Jaffe AS, Moeckel M, Giannitsis E, et al. In search for the Holy Grail: suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association. Eur Heart J Acute Cardiovasc Care 2014; 3:313.
- Keller T, Zeller T, Ojeda F, et al. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA 2011; 306:2684.
- Shave R, George KP, Atkinson G, et al. Exercise-induced cardiac troponin T release: a meta-analysis. Med Sci Sports Exerc 2007; 39:2099.
- Gupta S, de Lemos JA. Use and misuse of cardiac troponins in clinical practice. Prog Cardiovasc Dis 2007; 50:151.
- Müller-Bardorff M, Weidtmann B, Giannitsis E, et al. Release kinetics of cardiac troponin T in survivors of confirmed severe pulmonary embolism. Clin Chem 2002; 48:673.
- Sabatine MS, Morrow DA, de Lemos JA, et al. Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35. Eur Heart J 2009; 30:162.
- Kurz K, Giannitsis E, Zehelein J, Katus HA. Highly sensitive cardiac troponin T values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia. Clin Chem 2008; 54:1234.
- Turer AT, Addo TA, Martin JL, et al. Myocardial ischemia induced by rapid atrial pacing causes troponin T release detectable by a highly sensitive assay: insights from a coronary sinus sampling study. J Am Coll Cardiol 2011; 57:2398.
- Siriwardena M, Campbell V, Richards AM, Pemberton CJ. Cardiac biomarker responses to dobutamine stress echocardiography in healthy volunteers and patients with coronary artery disease. Clin Chem 2012; 58:1492.