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

Inclusion Criteria and Assessment of Study Quality

Inclusion criteria were designed to identify only those studies meeting Level 1b criteria, as defined by the Centre for Evidence-Based Medicine (cebm.jr2.ox.ac.uk/docs/levels.html). These inclusion criteria are:

• Prospective cohort study
• Adult patients with acute chest pain or other acute coronary syndrome
• At least 80% follow-up of patients
• Death, fatal or nonfatal MI, or any cardiac event at some point following hospital discharge

We excluded studies reporting only in-hospital outcomes and those without sufficient data to calculate sensitivity or specificity for at least one outcome.

Data Abstraction

Two independent investigators (either ME and DW or ME and LW) reviewed each article and abstracted data related to study quality, inclusion criteria, and test characteristics. Any discrepancies were resolved by consensus decision. The following data were abstracted: reference, study design, percentage of follow-up, outcomes measured, inclusion criteria for patients in the study, and data needed to calculate sensitivity or specificity.

Statistical Analysis

The primary outcomes were the test characteristics (sensitivity, specificity, post-test probability positive and negative, and positive and negative likelihood ratios* [LR+ and LR-, respectively]) for each combination of inclusion criteria, diagnostic test, and patient outcome.

Where possible, summary estimates of sensitivity and specificity were made using a DerSimonian and Laird random effects model. Sensitivity and specificity were pooled independently and weighted by the inverse of the variance using MetaTest software (version 0.6, Joseph Lau, MD, used with permission). If a fixed effects model and a random effects model calculated similar estimates of sensitivity or specificity, the statistic was deemed homogenous, and the more conservative random effects model result was reported. If the fixed effects model and the random effects model gave estimates that were different in a clinically meaningful way, the statistic was deemed heterogeneous, and only a range was reported.

Results

Twenty-eight studies met the inclusion criteria and had usable data for our systematic review.^6,8-34 Two studies used the research version of the Baxter Stratus enzyme-linked immunosorbent assay troponin I assay. A cutoff of 3.1 ng/mL corresponds to a cutoff of 0.6 in the commercial version of this assay.^15,19 One study²⁸ measured the troponin T level at 10 or more hours after the onset of chest pain. This was included with studies measuring the peak value within the first 24 hours. The study by Kerr and Dunt¹⁰ measured the troponin T value at 14 hours after the onset of chest pain. The study by Janorkar and colleagues³¹ followed patients for a variable length of time with a mean follow-up of 9 months and a standard deviation of 4 months.

In general, the studies used a wide variety of cutoffs, durations of follow-up, inclusion criteria, and outcomes. We have organized the results in 3 tables on the basis of the 3 populations studied in the available literature. [Table 1] shows data for patients with chest pain syndromes, [Table 2] for patients with unstable angina, and [Table 3] for patients with unstable angina or non-Q-wave MI. Unstable angina was generally defined as chest pain accompanied by electrocardiogram (ECG) changes but without evidence of MI, and non-Q-wave MI was defined on the basis of clinical and biochemical criteria for MI but without Q waves on the ECG.

Patients with Chest Pain

Troponin I. Only 1 study¹⁴ of patients with chest pain used the troponin I test, in this case a rapid bedside assay. It included 773 patients with chest pain and a normal ECG and used death or nonfatal MI as the outcome. The authors reported a sensitivity of 0.94, a specificity of 0.81, an LR+ of 5.0, and a very low LR- of 0.07.

Troponin T. Only 2 studies examined the accuracy of troponin T in patients with nontraumatic chest pain.^11,20 However, neither reported the rates of death or nonfatal MI during follow-up in a way that allowed calculation of sensitivity and specificity. The range of sensitivity for any cardiac event was from 0.31 to 0.54, the specificity from 0.78 to 0.92, the LR+ from 2.4 to 3.8, and the LR- from 0.6 to 0.7. Among patients with chest pain and a normal ECG, Hamm and coworkers¹⁴ reported an LR+ of 6.1 and an LR- of 0.2. Three studies included patients with chest pain who were admitted to rule out MI and were followed for 180 days to 2 years.^8-10 They reported a range of sensitivity of 0.52 to 0.67, specificity from 0.72 to 0.83, LR+ from 2.3 to 3.2, and LR- from 0.5 to 0.6.

Patients with Unstable Angina

Troponin I. Three studies of troponin I included patients with unstable angina and used the outcome of death during follow-up. The duration of follow-up ranged from 30 days to 9 months, and the cutoff for an abnormal test result was from 0.6 to 1.5 ng/mL.^19,21,31 The sensitivity varied widely from 0.5 to 1.0; however, 2 of the studies were small, with only 2 deaths in each study. The largest study found a sensitivity of only 0.52 and specificity of 0.73.²¹ For studies of troponin I using death or nonfatal MI as an outcome, results from 3 studies^15,18,22 could be combined, because the study designs were similar. They used a cutoff of 0.6 ng/mL, followed patients for 30 days, and used the peak troponin value in the first 8 to 72 hours. The summary test characteristics for these 3 studies were a sensitivity of 0.59, a specificity of 0.79, an LR+ of 2.8, and an LR- of 0.5.