The primary purpose of this review is to come up with approximations of diagnostics test accuracy, and hence compare troponin T with troponin I. Patients with suspected acute myocardial infarction (AMI) and acute chest pain have recently been evaluated using methods such as myocardial bound (CK-MB) or creatine kinase (CK). Diagnosis of AMI has been set at some criteria by the World Health Organization (WHAMIO). These criteria include history compatible with ischemia, typical electrocardiographic changes or elevation in blood test result. Troponin T and troponin I have recently been used to predict the adverse cardiac events as well as testing for AMI. However, troponin test is not easy to understand. The fraction of troponin used (T or I), the time since the start of myocardial or the criteria used to define abnormality makes the test characteristics largely different. Specificity and sensitivity will for instance increase or decrease depending on the increase or decrease of the cutoff number.
Depending on the number of hours since onset of the chest pain, sensitivity tends to increase since troponin depends on its discharge and myocardial cells damage. Thereafter, the sensitivity normally decreases following removal of troponins from the circulation. Nevertheless, “many of the reports on which current estimates of sensitivity and specificity are based do not report the time from the onset of symptoms or only provide the worst value in the first 24 hours” (Mark et al. 2001, p. 2). From time to time, description of the accuracy of the test is very critical especially for decision making in the emergency department (ED) where it is based on prior values.
Department of Primary Health Care (2011) established that, in the recent past, cardiac troponin (cTn) is preferred to creatine kinase for the purpose of diagnosis. It was found that the strong need for accurate testing of cardiac troponin was as a result of American College of Cardiology (ACC) and European Society of Cardiology (ESC) redefinition of myocardial infarction as “any amount of myocardial necrosis caused by ischaemia” (Department of Primary Health Care 2011, p.2). Troponin I (cTnI) and T (cTnT) indicates the degree of presence of myocardial necrosis by measuring the increase in the level of troponin. Although there are many studies that can measure troponin reliably, Department of Primary Health Care (2011) claimed that most of them were not able to produce result within a short duration of time. To simplify performance, they added that some tests for troponins have been modified in order to save time, besides using a blood sample that does not need pre-treatment and by reducing the probability of occurrence of operator error.
Myocardial infarction (MI) patients differ in respect to level of presentation that they undergo. While a small proportion shows no symptoms at all, others undergo severe or acute chest pain. The discomfort in the chest is usually heavy and instinctive and characteristically not localized well. An air hunger, sensation, or gas hang-up is experienced. Severe diaphoresis and shortness of breath is basically the only symptom. Sublingual nitroglycerin can be sued to relieve the symptoms which take place from minutes to hours. Both women and elderly patients with diabetes mellitus can experience difficulties being diagnosed with ordinary symptoms. During acute MI, there are no distinguishable characteristics for the physical examination. Chronological Measurements and electrocardiograms of troponin are very essential, even though the physical results and the history can spark doubts of acute MI.
Separation of MI from angina or other etiologies of patients with chest pains is therefore possible with cTn testing. An initial release of cTn which is enclosed inside the cell cytosol is produced by myocardial necrosis. cTn diffusion allows speedy detection which is sustained for a few hours. The cTn component usually contains three units, that is “Troponin T (TnT), Troponin I (TnI),and Troponin C (TnC)” (Department of Primary Health Care 2011, p.2). Detection of both TnI and TnT are done by three commercial tests. TnI is a protein with a 24KD and upholds a 40% structural peculiarity from the skeletal Troponin I. TnT is a protein with 37KD which is 10 to 30% different from troponin T isoforms from the skeletal region. TnI and TnT are released in diverse forms following a myocardial damage. “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” (Alpert 2000, p. 23).
In case of a chronic kidney disease (CKD), higher elevations of TnT has shown apparent bias compared to TnI which is known to set hurdles in MI in such a patient population. Elevations are not limited to finish stage disease, since TnT and TnI elevations are generally manifested in patients with predialysis, particularly those who are not associated with ACS.7 regardless of the type of heart disease, or if other factors are responsible for increased levels, free from ischemia- is an active field of scientific examination. Increased troponin in CKD patients makes it important to consider the diagnostic usefulness of cTn in patients with signs reminiscent of NSTEMI.
Prognostic as well as the diagnostics features of both TnI and TnT in CKD patients who do not exhibit ACS symptoms has made many author to conclude that “TnI had slightly better specificity, while TnT helped predict all-cause mortality” (Needham et al. 2004, p56). The factors that may affect the acknowledgement of TnT or TnI in the transmission include “the ability of a test system to detect the presence of troponin in both free and, completed forms, proteolysis of the cTn molecule, or modification of cTn” (Needham et al. 2004, p56). Availability of commercial cardiac specific troponin tests has eased the differentiation of MI from other chest pain causes. Definition of cardiac troponin has been made from a large number of studies as the “current gold standard test for diagnosis of acute MI” (Alpert 2000).
Recognition of TnI can also be influenced by the vender related disparities in consistency of assays as well as the similarity of antibodies. Apparently, unless further investigation on the superiority of either TnT ot TnI is conducted to produce a more compelling results, then the consensus remains that both TnI and TnT are rather comparable for diagnostics application. The aim of this study is to review the available existing literatures to compare troponin T with troponin I in diagnosis of myocardial infarction.
In order to get the information which discussed whether troponin T is better than troponin I in diagnosis of myocardial infarction, 6 databases were searched. Only the studies that were published after 2001 were included. Google scholar, Google, and DISCOVER were the main search engines which were used to search these articles. The search took more than two days because it was hard to find data published after 2001, most of the relevant data had been published between 1999 and 2000. Key words and databases used are available in appendix(x).
The characteristics of studies included in these studies included: studies published after 2001, studies published in English, patients with acute chest pain, articles available in full text; articles that measured the accuracy of myocardial infarction as the outcome, adults were included as the study population, and studies that compares nTn with nTi.
The evaluation tools that were used to evaluate the studies were obtained from Oxford University resources and were based on the results. Grading was determined using SIGN guidelines (2008), as shown in appendix (xx). It is recommendable for clinicians to interpret the outcome based on the number of hours following the onset of chest pain as much as it could be possible.
Twelve articles were identified, but seven were excluded as they did not meet the inclusion criteria. Three of them discussed the role troponin in general, without showing a clear comparison between troponin T and troponin I. One of them discussed the role of troponin T alone while another one discussed the role of troponin I. Two articles met all the inclusion criteria but could not be include because they did not meet time frame criteria. The four articles that met all the inclusion criteria scored highly with rating ranging from 1++ to 1-.The four studies clearly compared the role of triponin T and triponin I in diagnosis of myocardial infarction.
Four studies used small sample ranging between 51 and 102 patients, but 1 study used a big sample of up to 2220 patients. Two of the studies which established the accuracy of troponin revealed some differences. For instance, one study established that the overall accuracies of both cTnT and cTnT in regard to discrimination between diagnosis of AMI and AMI was very similar while another study established that Troponin I seemed to be more accurate. The troponin specificity and sensitivity seemed to follow a similar pattern in all the studies. If cTnI turned out to be less sensitive than cTnT, the condition was coupled with higher specificity of cTnI. Generally, the specificity of cTnI was slightly elevated than cTnT. When the sensitivity for both cTnI and cTnT increased from about 10% to 90% within a short period from the start of the chests pain, most of the studies revealed that specificity turns down slowly from about 87% to 80% for troponin T, but at about 94% for troponin I. Degree of troponin I elevation revealed a steady pattern of increase of risk of MI.
Discussion and conclusion
The existing data for the four studies which passed the inclusion criteria were summarized in regard to their existing data on “the accuracy of troponin T and I values as diagnostic tests for AMI for patients with acute chest pain” (Mark et al. 2001, p.5). The results obtained can help the clinicians for varied probability of AMI pretests and for determination of troponin I and troponin T in varied periods since the start of the chest pain. Although most of the studies tend to demonstrate that troponin I is better than troponin T in regard to ruling in MI, such results may not be very outright as the studies have been conducted on relatively small samples of population which may not make a good representative of the wider population.
The most critical significance for the clinicians from these studies is that “the sensitivity of the troponin tests, like that of any other cardiac enzyme, is highly dependent on the number of hours since the onset of chest pain” (Mark et al. 2001, p.4). The test fails to detect cases of AMI within the first 6 hours following the start of the chest pain. On the other hand, later after at least 12 hours following the onset of chest pain, the test becomes somewhat sensitive. The indication against the existence of AMI is shown by a negative troponin.
Stolear et al. (2000) established that TnT considerably correlates with the result and that it is an independent interpreter of cardiovascular actions. They emphasized cTnT is not caused by myocardial infarction alone. It is found that during sepsis, an increase in cTnT takes place as a result of patients with angina instability and without myocardial infarction. Essentially, cTnT was found to possess low specificity in renal failure but generally with high agree that cTnT on its own is not a valid test for diagnosing myocardial infarction in dialysis patients.
Mark et al. (2001) reports that a past meta–analysis publication of AMI diagnosis by use of troponins was made but it had multiple limitations. They add that the study used adverse cardiac events instead of diagnosis of AMI for its outcome, and that the study quality was not assessed. Mark et al. (2002) therefore suggest “the results of a systematic review of the literature documenting use of troponins for diagnosing AMI, with assessment of the quality of the studies and synthesis of results when appropriate (Mark et al. 2001, p. 2).
Schwarzmeier et al. (2005) provided that patients with body myositis inclusion do not exhibit TnI elevation without presence of myocardial damage, while TnT is elevated. This revealed that there could be a basis of false-positives for TnT. Cardiac troponin (cTn), compared to other biomakesr, has a specitivity and sensitivity with strong ability to detect very small amounts of myocardial damage. As such, many studies with evidence approach recommend the role played by cTn in diagnosis of MI in absence of apparent electrocardiographic (ECG) evidence; cTn is the preferable marker for MI diagnosis.
In a bid to tackle the disparities between the tests for TnT and TnI which are available commercially, several authors have compared directly, “the ability of TnT and TnI to accurately detect MI and guide triage in patients presented with suspected ACS” (Needham et al. 2004, p59). Most of the authors provide that “the assays are functionally equivalent for both diagnosis and risk assessment” (Collinson et al. 2001, p.12).
In a study examining the capability of cTn to establish the patients who can benefit from revascularization if indicated or coronary angiography, authors established that “low level elevations of either TnI or TnT equivalently identified at risk patients” (Morrow, 2001, p.56). In spite of demonstrating varied types of release patterns, the authors found that TnI and TnT interrelated adequately, in patients experiencing replacement of aortic valve (Hetland & Dickstein 2001).
In patients undergoing percutaneous coronary intervention, TnT and TnI were found to have equivalent prognostic information (Gurr and Leitz, 2004). TnI uses a variety of cut-points for the purpose of MI diagnosis. This is as a result of a couple of factors including “historical lack of a common TnI reference material for standardization, as well as calibration and antibody differences” (Gurr and Leitz, 2004, p. 25).
Although there exists a strong clinical consensus of both TnI and TnT assays, there exists some discrepancies between the two assays. Fieke et al. (2009) provides that use of cut points for TnI and TnT which have been recommended results in safe discharge of only the patients who have been tested with TnI, “as the quantitative value of TnI, but not for TnT, identified patients actually presenting with MI” (p. 23). On the other hand, the author states that a larger scale of study is essential to validate their results. Furthermore, “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)” (Speth, 2002 p.85). Elsewhere, studies have shown that both TnT and TnI are subdued in patients treated with heparin. This makes it unclear to conclude that TnI is preferred in clinical environment.
A common limitation in all the studies is the broad range of manufacturers, cutoffs, reagents, and processes used in the studies. Though these ideas may guide the physicians without such data, it is thought that each clinical center establish its own optimum cutoffs at each point and for each test. Although the sensitivity and specificity may be impacted by the differences in the manufacturing, the data did not provide any clear pattern, and quantification of the degree of such impact was worsened by lack of an apparent pattern and other aspects such as inclusion criteria, settings and study population. Besides being used for diagnosis of AMI, troponins can also be used for risk stratification. Future review may want to examine the ability of “troponin T and I to stratify patients into high-risk and low-risk groups for adverse cardiac events” (Mark et al. 2001, p.6)
Although the primary purpose of this review is to come up with approximations of diagnostics tests accuracy, it is recommendable to apply these results for further research guidance. Considering that the troponin T and I depends so much on the duration since the onset of the chest pain, when the blood is drawn, future research should always consider recording this time. In addition, the future researchers may consider “using WHO criteria for AMI, ensure blinding of the diagnosing physicians to the results of the troponin test, and provide adequate data for future systematic reviews and meta-analyses” (Mark et al. 2001, p.9). Finally, researchers should make sure that troponin T and I are measured so that their diagnosis can easily be compared. It is recommendable for clinicians to interpret the outcome based on the number of hours following the onset of chest pain as much as it could be possible.
Alpert, J, et al., 2000, ‘For the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction’, J Am Coll Cardiol vol. 2000, no. 36, pp. 959-969.
Collinson, PO, et al., 2001, ‘Clinical evaluation of the ACS:180 cardiac Troponin I assay’, Ann Clin Biochem. Vol. 38, pp. 509-19.
Department of Primary Health care, 2011, Point-of-care test for cardiac troponin, Oxford University, Oxford.
Fieke et al, 2009, ‘the heart in sporadic inclusion body myositis: a study in 51 patients’, Journal Of Neurology, vol.257, no. 3, pp. 447-451.
Hetland, O & Dickstein, K, 2001, ‘Cardiac troponins I and T in patients with suspected acute coronary syndrome: a comparative study in a routine setting’, Department of Clinical Chemistry, vol.44, no. 7, pp. 14-30
Mark, H, Ebell, MD, MS, Dan, F, Cheryl, A, Flynn, MD, 2001, ‘A Systematic Review of Troponin T and I for Diagnosing Acute Myocardial Infarction’, Journal Of Family Practice, Vol. 49, No. 6, pp. 2-6.
Morrow, DA, et al., 2001, ‘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 vol. 286, pp. 2405-2412.
Needham, DM, et al., 2004, Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature, Can J Cardiol, vol. 20, pp.12-12.
Schwarzmeier, JD, et al., 2005, ‘Positive Troponin T without cardiac involvement in inclusion body myositis’, Hum Pathol, vol. 36, pp. 917-21.
Speth, M, et al., 2002, ‘Interaction between heparin and cardiac troponin T and troponin I from patients after coronary bypass surgery’, Clinical Biochemistry vol. 35, pp. 355-362.