T roponin is the biomarker of choice for the detection of cardiac injury. To use it properly, one must understand how sensitive the specific assay being used is for detecting cardiac injury, the fact that elevated troponin levels are highly specific for cardiac injury and some critical issues related to the basic science of the protein and its measurement. In this article, we review the biology of troponin, characteristics of assays that measure serum troponin levels and how to apply these measurements to patients who present with possible cardiovascular disease. We also discuss other clinical situations in which troponin levels may be elevated.
The biology of troponinThe 3-unit troponin complex (troponin I, T and C) along with tropomyosin is located on the actin filament and is essential for the calcium-mediated regulation of skeletal and cardiac muscle contraction. 1 There are tissue-specific isoforms of troponin I, T and C. 2,3 Because the cardiac isoform of troponin C is shared by slow-twitch skeletal muscles, troponin C does not have cardiac specificity and thus is not used in assays for the diagnosis of cardiac injury. 4 There is one cardiac troponin I (cTnI) isoform in myocardial tissue. 5 This isoform has a post-translational tail of 32 amino acids on the N-terminus. 6,7 This sequence and the 42% and 45% dissimilarity with sequences of the other isoforms 8 have made possible the generation of highly specific monoclonal antibodies without cross-reactivity with other noncardiac forms. 9 Three genes control cardiac troponin T (cTnT). 10 These genes and alternative mRNA splicing produce a series of isoforms 10,11 with variable sequences close to the regions of the N-terminus and C-terminus. 10,12 Human cardiac muscle contains 4 troponin T isoforms, but only one is characteristic of the normal adult heart. 13,14 Highly specific antibodies have been made to the N-terminus-specific sequence of this cTnT isoform. 15 The skeletal isoforms present in the fetal heart are replaced by cTnI and cTnT late during fetal development. 16,17 cTnI is not expressed in skeletal muscle or other tissues during development 17 or in response to degenerative or regenerative muscle disease processes. 18 Thus, it is unlikely to be reexpressed in damaged tissues. The situation is more complex for cTnT. Re-expression of fetal forms occurs in cardiac tissue 12 and in diseased skeletal muscle. 19 With the firstgeneration cTnT assay, this problem was compounded by a nonspecific tag antibody that cross-reacted with troponin T in skeletal muscle. 20 Once this antibody was replaced by one with high specificity, false-positive elevations from skeletal muscle were eliminated. 15 Studies using immunohistochemistry and polymerase chain reaction have confirmed that these fetal isoforms are not detected by the assay used today. 21,22 Thus, the assay used to measure cTnT levels has cardiac specificity equivalent to that of assays for cTnI.
Characteristics of troponin assaysMost troponin is found in the 3-unit complex (troponin I, T and C) of the c...
