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Katherine Soreng, Ph.D. Bayer HealthCare LLC, Diagnostics Division, Tarrytown, New York


The commercial availability of rapid, sensitive, cardiac-specific troponin tests have revolutionized cardiac biomarker utility in the differentiation of myocardial infarction (MI) from other causes of chest pain. A large number of studies have resulted in the definition of cardiac troponin (cTn) as the current gold standard test for diagnosis of acute MI .1 Compared to other cardiac biomarkers such as CK-MB and myogloblin, cardiac troponin demonstrates superior sensitivity and specificity, with the ability to detect even minor amounts of myocardial damage. Hence, evidence-based studies support a role for cTn both in the diagnosis of MI, as well as for post-infarction risk assessment. Current guidelines from the European Society of Cardiology (ESC), American College of Cardiology (ACC) and American Heart Association (AHA) state that cTn is the preferred marker for MI diagnosis, particularly in absence of clear electrocardiographic (ECG) evidence.1,2 Patients with non-ST-segment elevation myocardial infarction (NSTEMI) often present with normal ECGSs, or inconclusive ECG irregularities such as T-wave inversion or ST-segment depression. Testing for cTn allows differentiation of MI from unstable angina (or other etiologies) in the NSTEMI patient presenting with chest pain. Myocardial necrosis (ischemia induced and other) produces an initial release of cTn contained within the cell cytosol. The diffusion rate of cytosolic cTn allows detection approximately six hours post-infarct, with a peak usually at 12-24 hours, and a gradual return to normal generally within 7-14 days. Secondary degradation of the myofibrils is thought to drive this extended release pattern, accounting for the elevated levels following depletion of cytosolic cTn. (Figure 1) It is frequently difficult to accurately assess the timeframe from symptom onset to physician examination because patients are often unable to correctly identify when symptoms first appeared, and a lack of clear symptoms often complicates interpretation. Therefore, current ESC/AHA/ACC guidelines recommend that serial troponin testing be utilized to confirm a diagnosis of MI in the setting of inconclusive ECG evidence, with a second sample usually collected at 6-12 hours post presentation.1,2 Serial testing is particularly useful for patients with either a negative or low-level initial cTn result in the presence of clinical symptoms suggestive of MI.

Figure 1 Cardiac Markers: Approximate Levels vs. Time of Onset Post MI

100 x ULRR
Cardiac Marker Concentration

Myoglobin CK-MB Troponin I Troponin T CK LDH

50 x ULRR

0 0 1 2 3 4
Time (days)



Troponin originates within the sarcomere of both cardiac and striated skeletal muscle. Each sarcomere is comprised of actin and myosin filaments, which interact to produce a muscle contraction. Each actin filament is associated with several tropomyosin molecules (Figure 2). In turn, each tropomyosin molecule is associated with a troponin complex, which regulates actin-myosin binding. The cTn complex is composed of three units: Troponin T (TnT), Troponin I (TnI), and Troponin C (TnC). While troponin is found in both skeletal and cardiac muscle, the high specificity of cTn for cardiomyocyte necrosis is conferred by unique peptide sequences present in cTn, but absent in skeletal troponin (sTn).

Figure 2 Schematic of Troponin Molecule


Head-to-tail overlap Actin Tropomyosin

Commercial tests exist for the detection of both TnI and TnT. In contrast, TnC is identical to skeletal troponin C, and hence is not utilized diagnostically for myocardial necrosis. TnI Is a 24 KD protein that maintains a 40% structural distinction from the skeletal Troponin I isoforms.3,4,5 TnT is a 37 KD protein that is 10-30% dissimilar from skeletal troponin T isoforms.5 Following myocardial damage, TnT and TnI are released in different forms. TnT is primarily found as the intact T:I:C complex, free TnT, and smaller immunoreactive fragments. TnI is released primarily as the intact T:I:C: and I:C complex. The binary form of cTnI:C appears to be the predominant molecule.

The development of tests with antibodies targeted to the cardiac-specific troponin peptide region allow for clear differentiation of cTn from sTn and the elimination of cross reactivity in the setting of skeletal muscle injury or disease. It is generally considered that a positive cTn represents irreversible damage to the cardiomyocyte, although it is possible that very low elevations of cTn could occur in the context of reversible damage. Commonly, the detection of elevated cTn results from necrosis induced by cardiac ischemia. However, other conditions can cause elevations in cTn as a result of damage to the heart independent of vascular disease. These conditions include acute pulmonary embolism, acute pericarditis, sepsis, heart failure, and myocarditis.6 Therefore, results of cTn testing should always be considered in the context of a comprehensive clinical examination.


Confounding circumstances exist in renal patients who often exhibit elevated cTn is the absence of clinically suspected myocardial ischemia, or other known causes of cTn elevation. In chronic kidney disease patients (CKD), a clear bias has been noted for higher elevations of TnT as compared to TnI, which can complicate diagnosis of a MI in this patient population. These elevations are not apparently confined to end stage disease, as elevations of both TnI and T (with a higher percentage of patients positive for TnT) are commonly found in predialyisis patients with no clinical suspicion of ACS.7 Whether cTn elevations in CKD patients represent undiagnosed coronary artery or other heart disease, or if increased levels result from other factors independent of silent ischemia, is an active area of clinical investigation. Because of elevations in troponin in CKD patients, the current diagnostic utility of cTn in these patients presenting with symptoms suggestive of NSTEMI must be carefully considered. In a review of diagnostic and prognostic test characteristics for both TnI and TnT in CKD patients without ACS symptoms, the authors found that TnI had slightly better specificity, while TnT helped predict all-cause mortality.8

There are a number of factors that may impact the recognition of TnI or TnT in circulation, including the ability of a test system to detect the presence of troponin in both free and, complexed forms, proteolysis of the cTn molecule, or modification of cTn. Vendor-based differences in assay standardization and antibody affinity also affect recognition of TnI in circulation. Historically, due to a licensing agreement, TnT has had a single commercial supplier, although this may change in the future. Many different manufacturers offer a test for TnI. To address potential differences between commercially available tests for TnI and TnT, multiple publications have directly compared the ability of TnI and TnT to accurately detect MI and guide triage in patients presenting with suspected ACS. Current publications overwhelmingly suggest that that the assays are functionally equivalent for both diagnosis and risk assessment.9,10, 11,12,13 Several studies have compared TnI to TnT in high-risk patients with suspected or known acute coronary syndrome (ACS). In three separate meta-analytic reviews of published trials using ACS patients, investigators concluded that TnI and TnT provided similar diagnostic and prognostic information14, 15, 16 (Table 1). In studies investigating the ability of cTn

Table 1 Meta-analysis of Troponin I and Troponin T in Acute Coronary Syndrome Patients Reference Title Prognostic role of troponin T versus Troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies. Cardiac troponins in suspected acute coronary syndrome: a meta-analysis of published trials. Conclusion Troponin T and I show similar prognostic significance for acute myocardial infarction or death in the same patients with unstable angina pectoris. The 2 markers are equally sensitive and specific, as confirmed by meta-analysis, and this supports a role in risk stratification. In conclusion, cTnI and cTnT provide similar information in ACS. In summary, our study found that among patients with possible cardiac ischemia or diagnosed unstable angina, an elevated troponin T or I indicates a significantly higher short-term risk of cardiac events including death and MI.

Olatidoye AG, et al. Am J Cardiol 1998;81:1405-10

Fleming SM, et al. Cardiology 2001;95:66-73

Heidenreich P, et al. J Am Coll Cardiol 2001;38:478-85

The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis.


to identify patients likely to benefit from both glycoprotein IIb/IIIa inhibitors and an early invasive strategy (coronary angiography and revascularization if indicated), investigators found that low level elevations of either TnI or TnT equivalently identified at risk patients.17,18 In patients undergoing aortic valve replacement, investigators concluded that TnI and TnT correlated sufficiently, despite demonstrating different patterns of release.19 In patients receiving percutaneous coronary intervention, TnI and TnT were found to provide equally predictive prognostic information.20 Assays for TnI utilize a number of different cut-points in the diagnosis of MI. This is the result of multiple factors, including historical lack of a common TnI reference material for standardization, as well as calibration and antibody differences. Multiple studies have investigated the clinical utility of individual vendor-specific cTn tests, providing evidence-based guides for diagnostic cut-points and risk assessment. Regardless of variability in clinical decision limits, all current cTn assays appear to have similar diagnostic and prognostic capacity in the clinical setting.


Despite the strong consensus of the clinical agreement between TnI and TnT, some minor differences are apparent between the two assays. Although the vast majority of studies support similar clinical utility between the two tests, a few exceptions have been published. At least one recent paper suggested that when using the recommended cutpoints for TnI and TnT, safe discharge of patients was only possible in patients tested with TnI, as the quantitative value of TnI, but not for TnT, identified patients actually presenting with MI. However, the authors do state that validation of their findings would require a larger scale study.21 In addition, TnT may be more susceptible to inhibition by heparin than TnI in patients where heparin is used as an anticoagulant (during open heart surgery or hospitalization).22 However, other evidence suggests that both TnT and TnI are inhibited in heparin treated patients, excluding a clear preferential use of TnI in this clinical context. In one publication, patients with inclusion body myositis had elevated TnT with no elevation in TnI in the absence of any indication of myocardial damage. Hence, a potential source of false-positives for TnT was identified.23 Unless further evidence-based investigations demonstrate compelling evidence of the superiority of one form of troponin testing over another (particularly using evidence- based approaches that best reflect clinical value), the clear current consensus appears to be that TnI and TnT are equivalent for both diagnostic and prognostic applications. The high specificity and sensitivity of cTn testing, along with the availability of rapid and cost-effective testing platforms, has positioned it as an indispensable tool available to the clinical practitioner.


1. Alpert J, et al. for the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969. 2. Braunwald E, et al. ACC/AHA guidelines for the management of patients with unstableangina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 2000;36:9701062. 3. Christenson RH, et al. Cardiac Troponin I measurement with the ACCESS immunoassaysystem: analytical and clinical performance characteristics. Clin Chem 1998;44:5260. 4. Bodor GS, et al. Development of monoclonal antibodies for an assay of cardiac Troponin Iand preliminary results in suspected cases of myocardial infarction. Clin Chem 1992;38:2203-14. 5. Mair J. Cardiac Troponin I and Troponin T: are enzymes still relevant as cardiac markers? Clin Chem Acta 1997;257:99-115. 6. Roongsritong C, et al. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest 2004;125:187784. 7. Abbas NA, et al. Cardiac troponins and renal function in nondialysis patients with chronic kidney disease. Clin Chem 2005;51:2059-66. 8. Needham DM, et al. Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature. Can J Cardiol 2004;20:1212-18. 9. Collinson PO, et al. Clinical evaluation of the ACS:180 cardiac Troponin I assay. Ann Clin Biochem 2001;38:509-19. 10. Morrow DA, et al. Ability of minor elevation of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 2001;286:240512. 11. Panteghini M, et al. Coronary angiographic findings in patients with clinical unstable angina according to cardiac Troponin I and T concentrations in serum. Arch Pathol Lab Med 2002; Apr;126(4):448-51. 12. Wu, AH. A comparison of cardiac Troponin T and cardiac Troponin I in patients with acute coronary syndromes. Coron Artery Dis 1999;10:69-74. 13. Hamm CW, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac Troponin T or Troponin I. N Engl J Med 1997;337:1648-53.


14. Fleming SM, et al. Cardiac troponins in suspected acute coronary syndrome: a meta-analysis of published trials. Cardiology 2001;95:66-73. 15. Olatidoye AG, et al. Prognostic role of Troponin T versus Troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies. Am J Cardiol 1998;81:1405-10. 16. Heidenreich P, et al., The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis. J Am Coll Cardiol 2001;38:478-85. 17. Morrow DA, et al. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 2001;286:2405-12. 18. Morrow DA, et al. Evaluation of the AccuTnI cardiac Troponin I assay for risk assessment in acute coronary syndromes. Clin Chem 2003;49:1396-98. 19. Gurr E and Leitz K. Comparison of cardiac Troponin T and I in healthy men and in aortic valve replacement. Clin Chem Lab Med 2004;42:1020-26. 20. Nageh T, et al. Cardiac Troponin T and I and creatine kinase-MB as markers of myocardial injury and predictors of outcome following percutaneous coronary intervention. Int J Cardiol 2003;92:285-93. 21. Eisenman A, et al. Are all troponin assays equivalent in the emergency department? Singapore Med J 2005;46:325-7. 22. Speth M, et al. Interacation between heparin and cardiac troponin T and troponin I from patients after coronary bypass surgery. Clinical Biochemistry 2002;35:355-62. 23. Schwarzmeier JD, et al. Positive Troponin T without cardiac involvement in inclusion body myositis. Hum Pathol 2005;36:917-21.


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