Correspondence

Troponin T Levels and Abciximab Therapy in Unstable Angina

N Engl J Med 1999; 341:1084-1085September 30, 1999

Article

To the Editor:

The accuracy of measurements of troponin T and creatine kinase MB fraction (CK-MB) is central to the results of the c7E3 Fab Antiplatelet Therapy in Unstable Angina (CAPTURE) study reported by Hamm et al. (May 27 issue).1 The authors state that “all serum samples were stored at –20°C or lower and transported to a central laboratory, where they were stored at –80°C until they were analyzed.”

It is recognized that total creatine kinase activity decreases steadily when stored at a temperature of –30°C (there is a decline in activity of 8.3 percent after four weeks).2 A similar reduction has been demonstrated for CK-MB under long-term storage at –20°C.3 The stability of troponin T is less well documented. Wu et al. found that levels in 38 of 40 samples stored at –20°C for eight weeks were within 10 percent of the original values.4 However, the stability of troponin T after storage for this amount of time is not known. Hamm et al. do not state how long the serum samples were stored at –20°C or lower, nor do they disclose whether all samples were stored for the same amount of time before analysis. The patients in the CAPTURE study were recruited between May 1993 and December 1995.5 Did the authors store additional serum samples from the patients to assess the degree of decay caused by long-term storage at very low temperatures? The decline in the activity of CK-MB, and possibly troponin T, may have affected the results of the study and should have been addressed in the study design.

Eli I. Lev, M.D.
Julio I. Osende, M.D.
Azfar G. Zaman, M.D.
Mount Sinai Medical Center, New York, NY 10029-6574

5 References

1. 1

   Hamm CW, Heeschen C, Goldmann B, et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med 1999;340:1623-1629
   Full Text | Web of Science | Medline

2. 2

   Lev EI, Hendler I, Siebner R, Tashma Z, Wiener M, Tur-Kaspa I. Creatine kinase activity decrease with short-term freezing. Enzyme Protein 1994;48:238-242
   Medline

3. 3

   Nealon DA, Henderson AR. Stability of commonly used thiols and of human creatine kinase isoenzymes during storage at various temperatures in various media. Clin Chem 1977;23:816-829
   Web of Science | Medline

4. 4

   Wu AHB, Valdes R Jr, Apple FS. Cardiac troponin-T immunoassay for diagnosis of acute myocardial infarction. Clin Chem 1994;40:900-907
   Web of Science | Medline

5. 5

   The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997;349:1429-1435[Erratum, Lancet 1997;350:744.]
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We share the concern of Lev et al. regarding the stability of cardiac markers in blood samples. However, according to our experience, the delay between the time the samples were obtained and analysis at the core laboratory has no critical effects. A major influence may be expected only when samples are repeatedly thawed and refrozen. The samples from the CAPTURE study, however, were thawed only once for the analysis we presented. We found no substantial difference in the average troponin T levels in samples from patients recruited in 1993 and those from patients recruited in 1995 (1993 [n=318], 0.36±1.04 ng per milliliter; 1995 [n=462], 0.35±0.94 ng per milliliter). Furthermore, a recent repeated analysis of samples from a previous study,1 which were stored at –80°C over a two-year period, showed no substantial decline in troponin T concentrations (1996, 0.24±0.64 ng per milliliter; 1998, 0.23±0.51 ng per milliliter).

Indeed, measurements of creatine kinase activity may be less stable over time. However, in our study, the CK-MB mass concentration was measured, which may be less sensitive to storage,2 and correlated well with the on-site measurements of creatine kinase activity (R²=0.92, P<0.001). Thus, we assume that the storage of the samples did not significantly influence the study results.

Christian W. Hamm, M.D.
Kerckhoff Heart Center, 61231 Bad Nauheim, Germany

Christopher Heeschen, M.D.
Stanford University School of Medicine, Stanford, CA 94305-5406

2 References

1. 1

   Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997;337:1648-1653
   Full Text | Web of Science | Medline

2. 2

   Gerhardt W, Katus H, Ravkilde J, et al. S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. Clin Chem 1991;37:1405-1411
   Web of Science | Medline