ABSTRACT
BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have received international endorsement as the standard biomarkers for detection of myocardial injury, for risk stratification in patients suspected of acute coronary syndrome, and for the diagnosis of myocardial infarction. An evidence-based clinical database is growing rapidly for high-sensitivity (hs) troponin assays. Thus, clarifications of the analytical principles for the immunoassays used in clinical practice are important. CONTENT: The purpose of this mini-review is (a) to provide a background for the biochemistry of cTnT and cTnI and (b) to address the following analytical questions for both hs cTnI and cTnT assays: (i) How does an assay become designated hs? (ii) How does one realistically define healthy (normal) reference populations for determining the 99th percentile? (iii) What is the usual biological variation of these analytes? (iv) What assay imprecision characteristics are acceptable? (v) Will standardization of cardiac troponin assays be attainable? SUMMARY: This review raises important points regarding cTnI and cTnT assays and their reference limits and specifically addresses hs assays used to measure low concentrations (nanograms per liter or picograms per milliliter). Recommendations are made to help clarify the nomenclature. The review also identifies further challenges for the evolving science of cardiac troponin measurement. It is hoped that with the introduction of these concepts, both laboratorians and clinicians can develop a more unified view of how these assays are used worldwide in clinical practice.
Subject(s)
Humans , Acute Coronary Syndrome , Biochemistry , Biomarkers , Diagnosis , Hope , Immunoassay , Myocardial Infarction , TroponinABSTRACT
Acute coronary syndromes [ACS] are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to pre-vent progression to infarction. The problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B-type natriuretic peptides can be shown to be diagnostic and prognostic in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS
ABSTRACT
To assess the effect of recalibration of the Roche 3rd-generation cTnT assay with recombinant human cardiac troponin T [cTnT] standards on clinical decision limits. Serum samples from 77 patients [66 +/- 16 years] admitted to the coronary care unit were assayed using the 2nd- and 3rd-generation cTnT assays. There was excellent agreement [r = 0.99 Spearman, 95% Cl 0.99-1.0; p = 0.0001, n = 153] between the 2nd- and 3rd-generation cTnT assays across the analytical range, but there was a curvilinear relationship between values. There was concordance between the 2nd- and 3rd-generation cTnT values in the range from 0 to 0.2 micro g/l. Above 0.2 micro g/l, however, there were increasing but predictable differences. There was no statistical difference between the 2nd- and 3rd-generation cTnT assays, demonstrated by a linear relationship below 0.2 micro g/l. This confirms that the 3rd-generation assay was calibrated to that of the 2nd-generation assay in the range of 0-0.2 micro g/l. The detection limit and upper reference limit of normal will be unaffected by this change in calibration. A non-linear relationship at higher 2nd-generation concentrations [0.2-25.0 micro g/l] was observed. Clinical decision limits up to 0.2 micro g/l associated with increased cardiac risk are unaffected by the assay calibration, but values greater than 0.2 micro g/I are affected