| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Letters |
1
North Shore Hospital, Auckland 1309, New Zealand
2
Tauranga Hospital, Bay of Plenty 3001, New Zealand
aAddress correspondence to this author at: Ward 3, North Shore Hospital, Private Bag 93-503, Takapuna, Auckland 1309, New Zealand. E-mail armstrog{at}whl.co.nz.
To the Editor:
The joint European Society of Cardiology/American College of Cardiology guidelines recently redefined myocardial infarction (1). The preferred biomarker for myocardial damage is a cardiac troponin, with an increased value being defined as a measurement exceeding the 99th percentile of a reference control group in the appropriate clinical setting, using an assay with a CV <10% at this value. No troponin assays appear to achieve this target (2). It has been recommended that reference values be determined and published in the peer-reviewed literature (1)(3). We were unable to find data for a reference control group specifically relating to the Bayer ACS:Centaur Troponin I (TnI) assay.
A factor that must be considered when defining the interval is the effect of specimen type on TnI concentrations close to the upper limit of the reference interval. Several studies have shown that the concentration of any of the troponins measured in heparin-plasma specimens may be markedly lower than in serum specimens (3). The ACS:Centaur TnI is reported to show mean plasma values 94% ± 3% compared with serum values, with 11% of plasma specimens having values >20% lower than serum specimens (4).
The aim of the present study was to define the TnI values in an apparently healthy, asymptomatic population, using the Bayer ACS:Centaur TnI assay. Specimens were collected into both heparin-containing and plain tubes to determine whether the specimen type would have any clinically meaningful effect on the reference values.
A total of 221 hospital staff members gave informed consent to take part in the study. To preserve confidentiality, no records were kept that allowed results to be linked back to the participants in the study. The sample population was self-selected in that they volunteered to take part in the study. The participants were 66% female, 25–65 years of age, and 92% of Caucasian ethnicity. Thus they were both younger and had a higher proportion of females compared with the population of patients who present at our hospitals with acute coronary syndromes. The use of older people as a reference group is problematic because of the increased likelihood of silent atherosclerotic plaque rupture (5). Such cases may falsely increase the range of troponin values obtained. Our study group was fit to work, and no one was aware of any medical condition that could have affected TnI concentrations.
Specimens were collected, centrifuged, and analyzed on the same day. The specimens were collected from two hospital sites and analyzed on two separate Centaur (Bayer) immunoassay analyzers. The assay method used was a two-site sandwich immunoassay with direct chemiluminometric detection; the assay used constant amounts of polyclonal goat anti-TnI antibody labeled with acridinium ester and monoclonal mouse anti-troponin antibodies coupled to paramagnetic particles. Calibrators and controls were analyzed in accordance with the manufacturer’s specifications. Twenty specimens from each site were exchanged and showed no significant difference in the values obtained using either instrument (P = 0.34, Wilcoxon signed-rank test).
Troponin data from plain and heparin-containing tubes showed means of 0.02 and 0.01 µg/L, medians of 0.0 and 0.0 µg/L, and ranges of 0–0.31 and 0–0.20 µg/L, respectively. The majority of specimens had TnI concentrations <0.15 µg/L. This is the limit of detection for the method used and is consistent with previous findings (6)(7).
The 99th percentile was 0.16 µg/L for both the serum and heparin-plasma specimens. The CV at the 99th percentile value of 0.16 µg/L was 22%. It reached the recommended value of 10% at 0.32 µg/L. The mean difference between heparin-plasma and serum samples was -0.01 µg/L (SD, 0.02 µg/L). The Bland-Altman plot in Fig. 1
shows the percentage difference between the paired serum and heparin-plasma specimens. At these low concentrations, the serum specimens tended to give higher values than heparin-plasma specimens. Although the difference was statistically significant (P <0.001, Wilcoxon signed-rank test), it is not sufficient to alter the clinical response to results close to these values and does not justify having two reference intervals related to each specimen type (8).
|
An increase in troponin above the 99th percentile (as per the recent guidelines) would mean that a TnI >0.16 µg/L is consistent with myocardial cell injury. This is close to the detection limit of the assay and is consistent with the concept that any detectable troponin in the circulation is probably abnormal.
Previous studies with this assay have found concentrations up to 0.21 µg/L in skeletal muscle injury and 0.17 µg/L in chronic renal failure (6). Our data suggest that an upper reference limit of 0.16 µg/L is more appropriate despite exceeding the recommended CV at this concentration. We believe that this change will significantly increase the sensitivity for detecting myocardial necrosis (1)(3).
In summary, we have shown that the upper reference limit for a healthy population is <0.16 µg/L for TnI concentrations measured using the Bayer ACS:Centaur method. The difference between TnI values obtained for serum or heparin-plasma specimens is only just significant at the low concentrations found in a healthy reference population. This difference is not likely to alter the clinical response and so does not justify having a different reference interval related to each specimen type.
References
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  B. H. Cuthbertson, A. R. Amiri, B. L. Croal, S. Rajagopalan, O. Alozairi, J. Brittenden, and G. S. Hillis Utility of B-type natriuretic peptide in predicting perioperative cardiac events in patients undergoing major non-cardiac surgery Br. J. Anaesth., August 1, 2007; 99(2): 170 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Adamczyk, R. J. Brashear, and P. G. Mattingly Choline concentration in normal blood donor and cardiac troponin-positive plasma samples. Clin. Chem., November 1, 2006; 52(11): 2123 - 2124. [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Croal, G. S. Hillis, P. H. Gibson, M. T. Fazal, H. El-Shafei, G. Gibson, R. R. Jeffrey, K. G. Buchan, D. West, and B. H. Cuthbertson Relationship Between Postoperative Cardiac Troponin I Levels and Outcome of Cardiac Surgery Circulation, October 3, 2006; 114(14): 1468 - 1475. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
