A Systematic Review of Troponin T and I Values as a Prognostic Tool for Patients with Chest Pain

Troponin T. Using unstable angina to determine inclusion and 30 days as the duration of follow-up, several studies found a low sensitivity of troponin T as a prognostic test. Three studies of unstable angina were quite similar in design and inclusion, using a cutoff of 0.1 ng/mL, blood drawn on admission to the emergency department, and an outcome of death at 30 days.^16,21,24 The summary test characteristics for these studies were a sensitivity of 0.63, a specificity of 0.66, an LR+ of 1.9, and an LR- of 0.6.

Depending on the combination of cutoff, timing of the blood draw, and duration of follow-up, a positive troponin T had a range of sensitivity from 0.38 to 0.63 and of specificity from 0.77 to 0.95 for the outcome of death or nonfatal MI at 30 days.^{6,18,19,23,26,27} Two studies 18.¹⁹ were similar in design, and their test characteristics could be combined (sensitivity=0.44, specificity=0.81, LR+=2.3, and LR-=0.7).

Patients with Unstable Angina or Non-Q-Wave MI

Troponin I .A positive troponin I in patients with unstable angina or non-Q-wave MI produced sensitivities from 0.72 to 0.78 and specificities from 0.59 to 0.60 for the outcome of death at 30 to 42 days.^18,34 For the outcome of death or nonfatal Ml using the same inclusion criteria, the range of sensitivity was from 0.59 to 1.00 and of specificity was from 0.60 to 0.74.^18,32,33

Troponin T. For an outcome of death, the LR+ was 1.3 to 1.8, and the LR- was 0.0 to 0.3.^18,29 The study²⁹ with an LR- of 0.0 had no false-negatives and a sensitivity of 1.0; it used a very low cutoff of 0.06 for an abnormal test result. Using the same cohort with a cutoff of 0.2, the investigators found a sensitivity of 0.72 and a specificity of 0.45. As expected, a lower cutoff improved the sensitivity of the test.

Discussion

Although one goal of systemic reviews is to pool study data from multiple sources to calculate summary measures of test accuracy, not all reviews can achieve that goal. In our study, a lack of standardization in study parameters limited our ability to combine summary estimates effectively. However, we have identified several important guidelines for clinicians using the troponin test and for future research in this area.

Most studies of the troponin test have evaluated it in patients with unstable angina or unstable angina and non-Q-wave MI. Although the test has some value in the non-Q-wave MI patients for identifying higher-risk and lower-risk groups, all such patients would generally be admitted to the hospital and followed closely. For primary care and emergency physicians evaluating a patient with chest pain in the emergency department, an important goal is to identify patients for whom adverse cardiac events such as death or nonfatal MI are unlikely in the near future. These patients could be sent home to follow up with their primary care physician and possibly undergo noninvasive testing as outpatients.

Unfortunately, only a few studies have included patients with chest pain or patients with chest pain and a normal ECG. The most useful study is that of Hamm and colleagues.¹⁴ In their study of 773 patients with chest pain and no ST elevation, troponin T and I both had a low LR- for the identification of patients at low risk of death or nonfatal MI in the 30 days following their episode of chest pain. Only 1 in 300 patients with a normal ECG and normal troponin I 6 hours after the onset of chest pain had an adverse outcome in the 30 days after hospital discharge and only 1 in 100 of those with normal ECG and normal troponin T. Although the troponin T test actually had a lower LR- and was potentially more useful, this test is not widely available in the United States. More studies of both troponin T and I are needed among patients with chest pain or chest pain and normal ECG to validate the findings of Hamm and coworkers.

Using a lower cutoff for abnormal with troponin T improves the sensitivity of the test. Lindahl and colleagues²⁹ found a sensitivity of 1.0 at a cutoff of 0.06 for the outcome of death in a study of patients with unstable angina or non-Q-wave MI; the sensitivity was only 0.86 for a cutoff of 0.2. Other pairs of studies had a similar pattern, which was expected. Future studies should report the sensitivity and specificity of the tests for several cutoffs, including lower values such as 0.05 ng/mL for troponin T.

Also, the sensitivity of troponin was improved when the peak value in the first 6 to 24 hours of admission was used instead of the value on admission to the emergency department. For example, among patients with unstable angina the sensitivity was 0.63 when blood was drawn on admission to the emergency department^16,21,24 and 1.0 when the peak value in the first 16 hours was used.²⁴ This makes physiologic sense, since patients presenting early in the course of their episode of unstable angina or MI may have undetectable levels of troponin which rise as the episode progresses.