Cardiac Troponins— How Useful Are they in Diagnosing or Excluding Myocardial Damage?

ABSTRACTS & COMMENTARY

Synopsis: In patients with acute coronary syndromes, cardiac troponin I provided useful prognostic information and permitted the early identification of patients with an increased risk of death.

Sources: Ohman EM, et al. N Engl J Med 1996;338: 1333-1341; Antman EM, et al. N Engl J Med 1996;338: 1342-1349.

In the absence of specific electrocardiographic changes, physicians have been totally dependent on serial measurements of serum levels of cardiac enzymes (i.e., usually creatinine kinase and its myocardial MG isoenzyme) to differentiate between unstable angina and acute myocardial infarctions in the absence of new Q wave development on the electrocardiogram. In recent years, enzyme immunoassays have been developed to measure serum levels of cardiac troponin T and cardiac troponin I.1,2,3 These proteins, along with troponin C, regulate the calcium-dependent interactions between myosin and actin, which are intimately involved in cardiac contraction and relaxation. Studies of peak troponin T levels measured within 24 hours after admission in small selected populations have found an increased number of cardiac events in patients with increased troponin T levels, even those without elevated CK-MB levels.4,5 Therefore, this test has improved sensitivity and specificity over CK-MB in the diagnosis and exclusion of myocardial injury.6,7

Ohman and colleagues representing the GUSTO-IIa investigators examined the value of serum levels of cardiac troponin T, serum creatinine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia. On admission, 289 of 801 patients had elevated troponin T levels, and the mortality rate within 30 days was significantly higher in these patients than patients with lower troponin T levels (11.8% vs 3.9%, respectively). Troponin T levels remained significantly predictive of 30-day mortality. Therefore, the authors conclude that the cardiac troponin T level was a powerful independent risk marker in patients who present with acute myocardial ischemia and that it permitted further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level measurements. Antman and associates studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction. The mortality rate at 42 days was found to be significantly higher in the 573 patients with elevated cardiac troponin I levels; equally important, there were statistically significant increases in mortality with increasing levels of cardiac troponin I. They conclude that in patients with acute coronary syndromes, cardiac troponin I provided useful prognostic information and permitted the early identification of patients with an increased risk of death.

COMMENT BY HAROLD L. KARPMAN, MD

Previous studies have suggested that the measurement of cardiac troponin T is useful in predicting risk in patients with unstable angina and that it appears to be superior to CK-MB in its predictive potential.4,5 Both Ohman et al’s prospective study and Antman et al’s retrospective study clearly demonstrate that the troponin T and troponin I levels were significantly predictive of relatively short-term mortality in patients with acute coronary syndromes even after the analysis was adjusted for electrocardiographic categories and for the CK-MB levels. A third study has also found that the risk of death from myocardial infarction during five months of follow-up was increased significantly with increasing levels of troponin T measured within the first 24 hours.8

Clinical studies have demonstrated improved time-dependent sensitivity and improved specificity for troponin I and troponin T compared to CK-MB in that patients who suffered an acute myocardial infarction had an earlier rise in troponin I than CK- MB. Based on these data, patients who present with chest pain without an ECG diagnostic of an acute myocardial injury, who are troponin I assay negative at eight hours, and who are chest pain free without evidence of ischemia on ECG are good candidates for early stress testing; if negative, discharge on medical management should be considered.

A stat troponin I assay (turnaround time approximately 60 min) obtained in the emergency department at the time of presentation will permit early identification of patients having an myocardial infarction; therefore, patients with a positive troponin I, if appropriate from a clinical point of view, may be sent directly to the cardiac catheterization laboratory for primary reperfusion therapy. Patients with negative assays should be treated with medical therapy for unstable angina or, if appropriate, for chest pain of non-cardiac origin. The troponin I assay will permit more accurate evaluations of patients with chest pain or abnormal electrocardiograms after trauma or injury (especially if they have a confusing elevated CK-MB level); if the troponin I assay is negative, an elevated CK-MB level will almost certainly be due to non-cardiac causes since a negative troponin I assay in this setting excludes myocardial injury and eliminates the need for any further testing. Finally, patients presenting with chest pain 2-6 days prior to admission may have sustained an acute myocardial infarction, but the CK-MB will have returned to normal levels in the majority of patients; since troponin I remained elevated for 4-6 days after a myocardial infarction, it is the preferred diagnostic test in this setting because a negative troponin I level excludes infarction in the previous five days in 96% of cases. Finally, it should be recognized that a negative troponin I assay does not exclude the diagnosis of unstable angina and does not exclude myocardial infarction of less than seven hours in duration.

In summary, it appears quite likely that measurements of serum cardiac troponins in serum in patients with acute coronary syndromes as they are admitted to the hospital or the emergency department are more specific than CK-MB and will permit identification of patients who are suffering or who have recently suffered an acute myocardial infarction. In addition, these measurements will help identify those at increased risk for subsequent cardiac complications, including death, even in those patients who do not have an elevated CK-MB fraction. The measurement of cardiac troponins will move rapidly from the teaching and university hospital environment into the community hospital and their emergency departments since these laboratory tests appear to be important in accurate diagnosis and in determining prognosis in patients presenting with acute coronary syndromes.

References

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3. Bodor GS, et al. Clin Chem 1992;38:2203-2214.

4. Hamm CW, et al. N Engl J Med 1992;327:146-150.

5. Ravkilde J, et al. Scand J Clin Lab Invest 1993;53: 677-685.

6. Adams JE 3d, et al. Circulation 1993;88:101-106.

7. Mair J, et al. Crit Rev Clin Lab Sci 1992;29: 31-57.

8. Lindahl B, et al. Circulation 1996;93:1651-1657.