Cardiac Troponin
1997; Elsevier BV; Volume: 111; Issue: 1 Linguagem: Inglês
10.1378/chest.111.1.2
ISSN1931-3543
AutoresChris S. Brown, Barry Bertolet,
Tópico(s)Cardiovascular Function and Risk Factors
ResumoFor years, physicians have relied upon serum markers to assist with the diagnosis of myocardial injury. The introduction of the serum glutamicoxaloacetic transaminase (SGOT) assay in 1954,1LaDue J.S. Wroblewshi F. Karmen A. Serum glutamic oxaloacetic transaminase activity in human acute transmural myocardial infarction [abstract].Science. 1954; 120: 497Crossref PubMed Scopus (217) Google Scholarfollowed by lactic dehydrogenase (LDH) isoenzymes in 1957,2Vesell E.S. Beam A.G. Localization of lactic acid dehydrogenase activity in serum fraction [abstract].Proc Natl Acad Sci USA. 1957; 94: 96Google Scholar and creatine kinase (CK) in 1966,3Vanderveen K.J. Willebrands A.F. Isoenzymes of creatinine phosphokinase in tissue extracts and in normal and pathological sera [abstract].Clin Chem Acta. 1966; 13: 312Crossref PubMed Scopus (134) Google Scholar revolutionized the diagnosis and management of patients with suspected myocardial infarction. Even though these assays were helpful, physicians demanded a more specific test for the diagnosis of acute myocardial infarction. In the mid-1970s, CK isoenzyme analysis (eg, CK-MB) was introduced,4Roberts R. Henry P.D. Witteveen SAGJ et al.Quantification of serum creatine phosphokinase (CPK) isoenzyme activity.Am J Cardiol. 1974; 33: 650-654Abstract Full Text PDF PubMed Scopus (125) Google Scholar and since has remained the gold standard for diagnosis of myocardial injury. However, with an increased application in a broader population, many patients without apparent cardiac disease were found to have elevations of CK-MB. Most often, these false elevations were secondary to skeletal muscle injury. Therefore, physicians have remained without a specific assay for myocardial injury … until now. Recently, troponin has been introduced as a marker of cardiac injury.5Katus H.A. Remppis A. Neumann F.J. et al.Diagnostic efficiency of troponin T measurements in acute myocardial infarction.Circulation. 1991; 83: 902-912Crossref PubMed Scopus (766) Google Scholar, 6Adams J.E. Bodor G.S. Davila-Roman V.G. et al.Cardiac troponin I: a marker with high specificity for cardiac injury.Circulation. 1993; 88: 101-106Crossref PubMed Google Scholar The troponin complex is located on the thin filament of the contractile apparatus in both striated and skeletal muscle tissue (Fig 1).7Katus H.A. Scheffold T. Remppis A. et al.Proteins of the troponin complex.Laboratory Medicine. 1992; 23: 311-317Crossref Scopus (69) Google Scholar Troponin consists of three proteins, troponin T, I, and C, that work together to regulate the force and velocity of muscle contraction by modulating the interaction of actin and myosin.6Adams J.E. Bodor G.S. Davila-Roman V.G. et al.Cardiac troponin I: a marker with high specificity for cardiac injury.Circulation. 1993; 88: 101-106Crossref PubMed Google Scholar, 7Katus H.A. Scheffold T. Remppis A. et al.Proteins of the troponin complex.Laboratory Medicine. 1992; 23: 311-317Crossref Scopus (69) Google Scholar The troponin complex is not found in smooth muscle. Differing isoforms of the troponin proteins are expressed in striated muscle as compared to skeletal muscle. Cardiac troponin T varies from skeletal troponin T by a unique set of amino acids, where cardiac troponin I differs from skeletal troponin I by a significant difference in the sequence of 31 amino acids.8Keffer J.M. Myocardial markers of injury evolution and insights.Am J Clin Pathol. 1996; 105: 305-320Crossref PubMed Scopus (117) Google Scholar These unique features can be exploited and allow for a very specific cardiac assay of myocardial injury. When myocyte damage occurs, the cellular membrane loses its integrity releasing its intracellular macromolecules into the interstitium. These macromolecules eventually find their way into the intravascular spaces and lymphatics. Cardiac troponin T (37,000 d) and troponin I (21,000 d), due to their smaller molecular weight when compared to CK (86,000 d), can be detected in the serum within a few hours after the onset of myocardial injury (mean, 4 h; range, 1 to 10 h). The enzyme concentration peaks from the second to fifth day, and unlike CK, remains elevated for 7 days allowing for the diagnosis of recent myocardial injury7Katus H.A. Scheffold T. Remppis A. et al.Proteins of the troponin complex.Laboratory Medicine. 1992; 23: 311-317Crossref Scopus (69) Google Scholar, 8Keffer J.M. Myocardial markers of injury evolution and insights.Am J Clin Pathol. 1996; 105: 305-320Crossref PubMed Scopus (117) Google Scholar, 9Cummins B. Auckland M.L. Cummins P. Cardiac-specific troponin I. radioimmunoassay in the diagnosis of acute myocardial infarction.Am Heart J. 1987; 113: 1333-1344Abstract Full Text PDF PubMed Scopus (399) Google Scholar, 10Bodor O.S. Porter S. Landt Y. et al.Development of monoclonal antibodies for an assay of cardiac troponin I and preliminary results in suspected cases of myocardial infarction.Clin Chem. 1992; 38: 2203-2214Crossref PubMed Scopus (399) Google Scholar (Fig 2). The major advantage of cardiac troponin involves its greater specificity for myocardial injury than CK or myoglobin. A study11Apple F.S. Voss B. Lund L. et al.Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.Clin Chem Acta. 1995; 237: 59-66Crossref PubMed Scopus (30) Google Scholar compared cardiac troponin I, CK-MB, and myoglobin levels in patients who presented to the emergency department with acute chest pain. All three markers were 100% sensitive in detecting the acute myocardial injury; however, the specificity of myoglobin for myocardial injury was only 61% compared with CK-MB at 86%, and cardiac troponin I at 92%. Of note, five of the six patients with elevated cardiac troponin I levels, but without other evidence of acute myocardial injury, had either recent cardiac surgery, myocardial contusion, or unstable angina which could explain the elevated levels.11Apple F.S. Voss B. Lund L. et al.Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.Clin Chem Acta. 1995; 237: 59-66Crossref PubMed Scopus (30) Google Scholar As reported by Bonnefoy and colleagues in this issue of CHEST (see page 15), of patients who had undergone cardioversion, 40% had elevation of total CK or myoglobin and 7% had elevation of the CK-MB consistent with acute myocardial injury. None of these patients had elevation of the cardiac troponin I levels, suggesting that cardiac troponin I may be a more specific marker of myocyte injury. Many times, the percent of CK-MB of the total CK rather than the absolute CK-MB value is used to differentiate skeletal muscle from myocardial injury; however, this practice may also lead to false conclusions. The CK-MB, total CK, and cardiac troponin I levels were measured in nine marathon runners. Seven had elevated CK and CK-MB without clinical or echocardiographic evidence of acute myocardial infarction. The percent CK-MB did not help differentiate the source of the elevated levels; whereas, cardiac troponin I was not elevated in any of these patients. Moreover, this same study also measured the CK, CK-MB, and cardiac troponin I levels of 209 patients with either acute skeletal muscle injury, chronic muscle disease, or prolonged hemodialysis. Elevations of CK-MB level were found in 59% of the patients with acute muscle injury, 78% of the patients with chronic muscle disease, and 4% of the patients with chronic renal failure. Cardiac troponin I levels were elevated in six patients; however, all were subsequently diagnosed during their hospital admission with acute myocyte injury.6Adams J.E. Bodor G.S. Davila-Roman V.G. et al.Cardiac troponin I: a marker with high specificity for cardiac injury.Circulation. 1993; 88: 101-106Crossref PubMed Google Scholar For similar reasons, it has also been difficult to diagnose myocardial infarction after surgery using CK/CK-MB. Adams et al12Adams J.B. Sicard O.A. Allen B.T. et al.Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I.N Engl J Med. 1994; 330: 670-674Crossref PubMed Scopus (501) Google Scholar diagnosed 8 of 108 patients with postoperative acute myocardial infarction based on finding new wall motion abnormalities on echocardiogram. All of these patients had elevated cardiac troponin I levels, whereas only 75% had an elevated CK-MB. Furthermore, 19 patients without echocardiographic evidence of myocardial infarction had elevated CK-MB levels compared to one with an elevated cardiac troponin I level. Of note, this one "false-positive" patient had a prolonged episode of hypotension. Therefore, the specificity of CK-MB was 81% and cardiac troponin I was 99%.12Adams J.B. Sicard O.A. Allen B.T. et al.Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I.N Engl J Med. 1994; 330: 670-674Crossref PubMed Scopus (501) Google Scholar Cardiac troponin also appears to be more sensitive than CK-MB, particularly for minor myocardial injuries. In a series of 25 cardiac patients who had just successfully completed coronary angioplasty, 44% had elevated cardiac troponin T levels; whereas 16% of these patients had elevated CK levels with only half having an MB fraction greater than 5%.13Karim M.A. Shinn M. Oskarsson H. et al.Significance of cardiac troponin T release after percutaneous transluminal coronary angioplasty.Am J Cardiol. 1995; 76: 521-523Abstract Full Text PDF PubMed Scopus (80) Google Scholar In another series, 32 of 209 critically ill patients (15.3%) had elevated cardiac troponin I levels, and 20 of those 32 had completely unrecognized acute cardiac events masked by their coexisting medical illnesses. This lack of sensitivity was due primarily to the physicians not believing that the elevated CK-MB represented myocardial injury, as well as the result of CK measurements being improperly timed to detect the event. However, in some, the CK-MB level was never elevated. These patients with elevated troponin I levels were hypotensive more frequently, required longer intensive care stays, and had higher mortality rates.14Guest T.M. Ramanathan A.V. Tuteur P.O. et al.Myocardial injury in critically ill patients a frequently unrecognized complication.JAMA. 1995; 273: 1945-1949Crossref PubMed Scopus (310) Google Scholar Cardiac troponin appears to be a more sensitive indicator of coronary reperfusion. Serial measurements of myoglobin, CK-MB, and cardiac troponin I were obtained in 25 acute myocardial infarction patients who had received thrombolytic therapy. Coronary reperfusion was determined by 90-min coronary angiography. The change (large peak) in cardiac troponin I levels was found to be the most sensitive marker for reperfusion at 82% compared to myoglobin at 76% and CK-MB at 65%.15Apple F.S. Henry T.D. Berger C.R. et al.Early monitoring of serum cardiac troponin I for assessment of coronary reperfusion following thrombolytic therapy.Am J Clin Pathol. 1996; 105: 6-10Crossref PubMed Scopus (55) Google Scholar In a similar study comparing cardiac troponin T, CK-MB, and myoglobin, cardiac troponin T was found to be the most sensitive noninvasive marker of reperfusion.11Apple F.S. Voss B. Lund L. et al.Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy.Clin Chem Acta. 1995; 237: 59-66Crossref PubMed Scopus (30) Google Scholar Unlike CK-MB, cardiac troponin has been shown to be an independent prognostic indicator in patients with unstable angina. Of 104 unstable angina patients admitted into the hospital, 27 had elevated troponin T levels. Most of these patients subsequently had a clinical event within the next month—30% experienced a myocardial infarction, 20% developed refractory angina, and 67% required a revascularization procedure. In this group of cardiac patients, an elevated cardiac troponin T level denoted a poor short-term prognosis, and this may be a marker for an atherosclerotic plaque which is particularly fragile.16Wu A.H. Abbas S.A. Green S. et al.Prognostic value of cardiac troponin T in unstable angina patients.Am J Cardiol. 1995; 76: 970-972Abstract Full Text PDF PubMed Scopus (106) Google Scholar In retrospect, these patients were actually "misdiagnosed" by CK-MB as only having unstable angina and rather should have been labeled as non-Q-wave myocardial infarction survivors. Present utility of cardiac troponin is outlined in Table 1. The only disadvantage of cardiac troponin is in its utility for the diagnosis of reinfarction. Due to its long half-life, a second myocardial infarction within 7 to 10 days of the first may be difficult to diagnose using cardiac troponin assays alone.Table 1Uses of Cardiac TroponinDiagnosis Acute MI (0-24 h) Recent MI (24-168 h) Cardiac contusion Perioperative MI Cardiac allograft rejectionClinical assessment Significance of side-branch occlusion during coronary revascularization procedures Assessment of coronary artery reperfusion following thrombolytic therapy Open table in a new tab No head-to-head comparison studies have been performed; however, the assay for cardiac troponin I appears to have several advantages over cardiac troponin T. The assay for cardiac troponin T has been positive in patients with diseased skeletal muscles.17Jaffe A.S. In search of specificity: the troponins.ACC Cur J Rev. 1995; 5: 29-33Crossref Scopus (7) Google Scholar One such example is that of a patient with polymyositis and no apparent cardiac disease.18Kobayashi S. Tanaka M. Tamura N. et al.Serum cardiac troponin T in polymyositis/dematomyositis [letter].Lancet. 1992; 340: 726Abstract PubMed Scopus (95) Google Scholar Also, troponin T has been shown to be elevated in patients with regenerating skeletal muscles.19Saggin L. Gorza L. Ausoni S. et al.Cardiac troponin T in developing, regenerating, and denervated rat skeletal muscle.Development. 1990; 110: 547-554PubMed Google Scholar The other disadvantage is the observance that cardiac troponin T is elevated in patients with chronic renal insufficiency. In a preliminary report, 26 blood samples from chronic dialysis patients without evidence of acute myocardial injury were elevated. Sixty-nine percent had elevated troponin T, and none had elevated troponin I levels. Some hypothesize that the cardiac troponin T levels are elevated in these patients due to a myopathy with muscle regeneration, which is known to occur with uremia.20McLaurin M.D. Apple F.S. Herzog C.A. et al.Cardiac troponin I, T, and CK-MB in chronic hemodialysis.Circulation. 1995; 92: I-80Google Scholar, 21Li D. Jailal I. Keffer J. Greater frequency of increased troponin T than increased cardiac troponin I in patients withchronic renal failure.Clin Chem. 1996; 42: 114-115PubMed Google Scholar In conclusion, cardiac troponin has been shown to be a more sensitive and specific marker of myocyte injury than myoglobin or CK-MB. The assay for cardiac troponin I currently seems to be the most sensitive and specific biochemical marker for the diagnosis of myocardial injury; however, in the absence of muscle disease or renal failure, the assay for cardiac troponin T seems to be adequate. It is now time for CK-MB to take its place in history along with SGOT and LDH. Cardiac troponin will certainly become the most reliable biochemical aid in the diagnosis of cardiac injury.
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