A Systematic Review of Troponin T and I for Diagnosing Acute Myocardial Infarction

Test Accuracy by Time from the Onset of Symptoms

Figure 1 shows the sensitivity for studies of troponin T using cutoffs of 0.1,7,8,14 0.2,6,14,19 and 0.519 plotted against the number of hours from the onset of chest pain. Specificity was similar for all 3 cutoffs and is plotted as a single line. The authors of most of these studies evaluated the widely used enzyme-linked immunoassay test from Boehringer-Mannheim. The following equations plot the logarithmic curves for sensitivity shown on the graph and allow for the calculation of the sensitivity and specificity of troponin T for any number of hours following the onset of chest pain (note that these equations are only valid over the range for which data are available; ie, 0-12 hours from the onset of chest pain):

Cutoff 0.1: sensitivity=(-0.0011 × hours2) + (0.0634 × hours) + 0.4036

Cutoff 0.2: sensitivity=(-0.0132 × hours2) + (0.2363 × hours) - 0.0862

Cutoff 0.5: sensitivity=(-0.0111 × hours2) + (0.223 × hours) - 0.0981

All cutoffs: specificity=(-.0084 × hours) + 0.8821

Data from high-quality studies were more limited for troponin I. Only 4 level I studies reported data for troponin I,^10,11,13,15 and only one of these reported results for sensitivity and specificity for different times from the onset of symptoms. The authors of that study¹³ only reported the sensitivity and specificity for ranges of 6, 12, 24, and 72 hours and used a cutoff of 2.5 ng/mL. Sensitivity was 17% in the 0 to 6-hour range, 92% in the 6 to 12-hour range, and 100% for the highest value in the 12 to 24-hour range. The specificity was 95% from 0 to 12 hours, and 98% from 12 to 24 hours. The corresponding positive and negative likelihood ratios are 3.4 and 0.9 for the 0 to 6-hour range, 18.4 and 0.08 for the 6 to 12-hour range, and 50 and 0.01 for the 12 to 24-hour range. A single level II study of a bedside troponin I test²⁴ measured the sensitivity as a function on the hours from the onset of chest pain, using a cutoff of 0.1 ng/mL. This graph is shown in Figure 2. The formula for sensitivity is:

Sensitivity=(-0.0128 × hours2) + (0.2438 × hours) - 0.0971

Sensitivity does not exceed 80% until 5 hours after the onset of chest pain. Specificity was not reported in this study.

Test Accuracy by Time After Admission

The authors of 5 studies reported the sensitivity and specificity measured from the time of arrival at the ED. Summary estimates of the sensitivity and specificity for troponin T, using a cutoff of 0.2 ng/mL at the time of admission, were 33% and 93% (values from the fixed effects model were 35% and 94%). The corresponding positive and negative likelihood ratios are 4.7 and 0.7, and the weighted area under the ROC curve is 0.77.^{14,18,19,22,23} Using the peak value of troponin T in the first 24 hours and a cutoff of 0.2, the sensitivity and specificity are 98% and 87% (values from the fixed effects model were 98% and 89%). The corresponding positive and negative likelihood ratios are 7.5 and 0.02, and the weighted area under the ROC curve is 0.99.^19,16,20

Discussion

We have summarized the existing data on the accuracy of troponin T and I values as diagnostic tests for AMI for patients with acute chest pain. These data are summarized for clinicians in Table 2. The sensitivities and specificities in Table 2 are estimated from the best-fit curves shown in Figure 2. Note that for troponin I, sensitivity data are from one study²⁴ and specificity from another.¹³ Nomograms can help physicians interpret the results of troponin T and troponin I at different times from the onset of chest pain and for different pretest probabilities of AMI.* Although troponin I appears to be better at ruling in MI than troponin T, these results are based on a single small study.

The most important take-home message for clinicians 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. The test is insensitive (ie, will miss many cases of AMI) within the first 6 hours after the onset of chest pain, when patients often present to the ED. However, by 12 or more hours after pain onset the test is quite sensitive, and a negative troponin value is strong evidence against the presence of AMI.

Diagnostic tests are symmetric if a positive test result as effectively rules in disease as a negative test result rules it out. For example, a test with a positive likelihood ratio of 5 and a negative likelihood ratio of 0.2 (1/5) would be symmetric. Examination of the likelihood ratios reveals that the troponin tests are asymmetric with respect to the positive and negative likelihood ratios. However, this relationship is not consistent. Troponin T and I are very useful at ruling out AMI when the value is negative at 10 or more hours from the onset of chest pain (negative likelihood ratio 0.1). However, a negative test value early in the course of the episode of chest pain does very little to reduce the likelihood of AMI. A positive troponin T value, however, is only moderately useful at ruling in AMI when blood was drawn 6 or more hours after the onset of pain (positive likelihood ratio=~5). Although a positive troponin I value from blood drawn 6 or more hours after the onset of pain appears to be very useful at ruling in AMI (positive likelihood ratio=~15), this is based on one relatively small study. While asymmetry is neither good nor bad, it is important to recognize when interpreting test results.