It’s Time for a Change to a Troponin Standard
Authors: Allan S. Jaffe, Jan Ravkilde, Robert Roberts, Ulf Naslund, Fred S. Apple, Marcello Galvani, Hugo Katus
Journal: Circulation (2000)

ecently, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) convened a conference to discuss refinements in the diagnosis of acute myocardial infarction.The panel on biochemistry considered issues related to the use of marker proteins.We were guided predominantly by the science of the area.We were also cognizant of the impact that changes in the standards would have on epidemiology, clinical trials, education of physicians, and patient care.Our recommendations will be incorporated, with the recommendations of the other panels, into a position paper for the ESC and the ACC.However, the members of the biochemistry group decided to express the opinions we felt were important in this area independently.Our thinking does not represent the position of the ESC, the ACC, or of the conjoint task force.Many modifications of the original World Health Organization criteria for acute myocardial infarction 1 have been accepted and incorporated into the ESC/ACC criteria; some deletions have also occurred.Until recently, most markers were detected using enzymatic activity; detection of the protein concentration now is preferred.Thus, it is more appropriate to refer to molecules released into the circulation as a consequence of cardiac injury as biochemical diagnostic markers or biomarkers.In this editorial, we emphasize issues related to the biochemical diagnosis of acute myocardial infarction.New and improved plasma biomarkers (troponins) with better sensitivity and specificity will be emphasized in preference to markers such as total creatine kinase (CK), CK-MB, lactate dehydrogenase, and aspartate aminotransferase.Rapid assays for the early detection of infarction that may be helpful will be delineated, and the use of the troponin markers to aid in the risk stratification of patients with acute coronary syndromes will be recommended. Specific Recommendations Biomarker IncreasesDetectable increases in the biomarkers of cardiac injury are indicative of injury to the myocardium, but elevations are not synonymous with an ischemic mechanism of injury.Therefore, increases do not now and did not in the past mandate a diagnosis of myocardial infarction. 2,3 Cardiac Troponins Are Preferred MarkersCardiac troponins (I or T) are the preferred markers for the diagnosis of myocardial injury. 4 -6 The improved tissue specificity of the troponins compared with CK-MB and other conventional markers is well established.Initially, because of assay difficulties, some questioned the specificity of cardiac troponin T (cTnT), especially in patients with renal failure. 7However, immunohistochemical and molecular studies on the skeletal muscle from such patients has established that the isoforms of cTnT that are re-expressed in response to injury are not detected with the second and third generation assays for cTnT. 8,9Thus, increased plasma levels of cTnI or cTnT are highly specific for release from the myocardium.This advantage has been established in clinical studies.It is now clear that when conjoint skeletal muscle and cardiac injury is present, the improved specificity of the troponins reduces the number of false-positive results while maintaining high sensitivity. 6,10 -12 This improved specificity is coupled with improved sensitivity. 4 -6,13 This fact, along with the prolonged time window 14,15 during which troponin markers are elevated, allow for the detection of a larger number of patients at risk for subsequent adverse cardiac events. 16 -19 For these reasons, troponins should be the preferred marker for diagnostic use.Laboratories should move as rapidly as feasible to implement cTnI or cTnT as the new standard.For clinical laboratories that cannot move as rapidly as others to implement this new standard, CK-MB values should be used. 20CK-MB has less tissue specificity than the troponins 8,11 ; however, the data documenting its specificity for irreversible injury is more robust. 21Most clinicians and laboratorians prefer to use mass assays.Several markers should no longer be used to evaluate cardiac disease.These include total CK, aspartate aminotransferase, total lactate dehydrogenase, and lactate dehydrogenase isoenzymes.These markers have poor specificity for the detection of cardiac injury because of their wide tissue distribution.Because total CK has served as the gold standard for so many years, some may wish to continue to measure it to allow for comparisons over time.This is a reasonable rationale for those conducting trials and epidemiologists.If used, a high threshold for abnormality (Ն2-fold increase)