Semin Vasc Med 2003; 03(4): 363-374
DOI: 10.1055/s-2004-815694
RISK STRATIFICATION

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Troponins in Acute Coronary Syndromes

Benjamin M. Scirica, David A. Morrow
  • Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA
Further Information

Publication History

Publication Date:
03 February 2004 (online)

ABSTRACT

Delivering superior clinical specificity and sensitivity for myocardial necrosis, cardiac troponin has replaced creatine kinase-MB as the preferred biomarker for establishing the diagnosis of myocardial infarction. On the basis of expert recommendations, present convention sets the diagnostic decision-limit for each assay at the 99th percentile of troponin levels in an apparently healthy reference population. Owing to a lack of standardization between different assays, this level, corresponding to the 99th percentile, will vary depending upon the manufacturer. Among patients presenting with an acute coronary syndrome (ACS), even low-level elevations of cardiac troponin T or I are associated with higher risk of death and recurrent ischemic events compared with patients with a troponin level below the appropriate decision limit. Renal failure does not appear to diminish the prognostic value of troponins among patients with a high clinical probability of ACS. In addition, patients with elevated levels of troponin appear to gain the most benefit from more aggressive medical therapy with antithrombin and antiplatelet medications as well as an early invasive management strategy. Cardiac troponins offer extremely high tissue specificity but do not discriminate between ischemic and nonischemic mechanisms of myocardial injury; thus, presently the clinician must assess whether a patient's presenting symptoms are consistent with ACS. It is possible that future generations of troponin assays will detect specific post-translational modifications of troponins that may increase the analytic sensitivity for myocardial damage and offer insight into the timing and mechanism of myocardial injury.

REFERENCES

  • 1 Hamm C W, Braunwald E. A classification of unstable angina revisited.  Circulation . 2000;  102 118-122
  • 2 Scirica B M, Cannon C P, Antman E M. et al . Validation of the thrombolysis in myocardial infarction (TIMI) risk score for unstable angina pectoris and non-ST-elevation myocardial infarction in the TIMI III registry.  Am J Cardiol . 2002;  90 303-305
  • 3 Cannon C P. Evidence-based risk stratification to target therapies in acute coronary syndromes.  Circulation . 2002;  106 1588-1591
  • 4 Braunwald E, Antman E M, Beasley J W. et al . ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina).  J Am Coll Cardiol . 2002;  40 1366-1374
  • 5 Morrow D A. Troponins in patients with acute coronary syndromes: biologic, diagnostic, and therapeutic implications.  Cardiovasc Toxicol . 2001;  1 105-110
  • 6 Morrow D A, Braunwald E. Future of biomarkers in acute coronary syndromes: moving toward a multimarker strategy.  Circulation . 2003;  108 250-252
  • 7 Ross R. Atherosclerosis-an inflammatory disease.  N Engl J Med . 1999;  340 115-126
  • 8 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes.  Circulation . 2001;  104 365-372
  • 9 Hamm C W, Ravkilde J, Gerhardt W. et al . The prognostic value of serum troponin T in unstable angina.  N Engl J Med . 1992;  327 146-150
  • 10 Ahmed S A, Williamson J R, Roberts R, Clark R E, Sobel B E. The association of increased plasma MB CPK activity and irreversible ischemic myocardial injury in the dog.  Circulation . 1976;  54 187-193
  • 11 Ishikawa Y, Saffitz J E, Mealman T L, Grace A M, Roberts R. Reversible myocardial ischemic injury is not associated with increased creatine kinase activity in plasma.  Clin Chem . 1997;  43 467-475
  • 12 Wu A H, Ford L. Release of cardiac troponin in acute coronary syndromes: ischemia or necrosis?.  Clin Chim Acta . 1999;  284 161-174
  • 13 Chocron S, Alwan K, Toubin G. et al . Effects of myocardial ischemia on the release of cardiac troponin I in isolated rat hearts.  J Thorac Cardiovasc Surg . 1996;  112 508-513
  • 14 Chen Y, Serfass R C, Mackey-Bojack S M, Kelly K L, Titus J L, Apple F S. Cardiac troponin T alterations in myocardium and serum of rats after stressful, prolonged intense exercise.  J Appl Physiol . 2000;  88 1749-1755
  • 15 Antman E M, Grudzien C, Mitchell R N, Sacks D B. Detection of unsuspected myocardial necrosis by rapid bedside assay for cardiac troponin T.  Am Heart J . 1997;  133 596-598
  • 16 Carlson R J, Navone A, McConnell J P. et al . Effect of myocardial ischemia on cardiac troponin I and T.  Am J Cardiol . 2002;  89 224-226
  • 17 Thayapran N, Prigent F, Steingart R, Feng Y J, Lowenkron D, Wu A H. Is there a release of cardiac troponin during exercise testing?.  (abstract). Circulation . 1997;  96 I-461
  • 18 Kwong R Y, Schussheim A E, Rekhraj S. et al . Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging.  Circulation . 2003;  107 531-537
  • 19 Jaffe A S, Ravkilde J, Roberts R. et al . It's time for a change to a troponin standard.  Circulation . 2000;  102 1216-1220
  • 20 The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Myocardial infarction redefined-a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.  J Am Coll Cardiol . 2000;  36 959-969
  • 21 Shi Q, Ling M, Zhang X. et al . Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays.  Clin Chem . 1999;  45 1018-1025
  • 22 Morrow D A, Rifai N, Tanasijevic M J, Wybenga D R, de Lemos A J, Antman E M. Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B substudy.  Clin Chem . 2000;  46 453-460
  • 23 Labugger R, Organ L, Collier C, Atar D, Van Eyk E J. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction.  Circulation . 2000;  102 1221-1226
  • 24 Katrukha A G, Bereznikova A V, Filatov V L. et al . Degradation of cardiac troponin I: implication for reliable immunodetection.  Clin Chem . 1998;  44 2433-2440
  • 25 Heidenreich P A, Alloggiamento T, Melsop K, McDonald K M, Go A S, Hlatky M A. The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis.  J Am Coll Cardiol . 2001;  38 478-485
  • 26 Heeschen C, Hamm C W, Bruemmer J, Simoons M L. Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial.  J Am Coll Cardiol . 2000;  35 1535-1542
  • 27 James S K, Armstrong P, Barnathan E. et al . Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome. A GUSTO-IV substudy.  J Am Coll Cardiol . 2003;  41 916-924
  • 28 Venge P, Lagerqvist B, Diderholm E, Lindahl B, Wallentin L. Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy).  Am J Cardiol . 2002;  89 1035-1041
  • 29 Morrow D A, Cannon C P, Rifai N. et al . Ability of minor elevations of troponin I and T to identify patients with unstable angina and non-ST elevation myocardial infarction who benefit from an early invasive strategy: results from a prospective, randomized trial.  JAMA . 2001;  286 2405-2412
  • 30 Ohman E M, Armstrong P W, Christenson R H. et al . Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.  N Engl J Med . 1996;  335 1333-1341
  • 31 Ohman E M, Armstrong P W, White H D. et al . Risk stratification with a point-of-care cardiac troponin T test in acute myocardial infarction. GUSTOIII Investigators. Global Use of Strategies To Open Occluded Coronary Arteries.  Am J Cardiol . 1999;  84 1281-1286
  • 32 Giannitsis E, Muller-Bardorff M, Lehrke S. et al . Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction.  Circulation . 2001;  104 630-635
  • 33 Kurowski V, Hartmann F, Killermann D P. et al . Prognostic significance of admission cardiac troponin T in patients treated successfully with direct percutaneous interventions for acute ST-segment elevation myocardial infarction.  Crit Care Med . 2002;  30 2229-2235
  • 34 Hamm C W, Heeschen C, Goldmann B. et al . Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) study investigators.  N Engl J Med . 1999;  340 1623-1629
  • 35 Topol E J. Inflammation and embolization in ischemic heart disease.  J Invasive Cardiol . 2000;  12 (suppl B) 2B-7B
  • 36 Topol E J, Yadav J S. Recognition of the importance of embolization in atherosclerotic vascular disease.  Circulation . 2000;  101 570-580
  • 37 Heeschen C, van Den Brand J M, Hamm C W, Simoons M L. Angiographic findings in patients with refractory unstable angina according to troponin T status.  Circulation . 1999;  100 1509-1514
  • 38 Wong G C, Morrow D A, Murphy S. et al . Elevations in troponin T and I are associated with abnormal tissue level perfusion: a TACTICS-TIMI 18 substudy. Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction.  Circulation . 2002;  106 202-207
  • 39 Matetzky S, Sharir T, Domingo M. et al . Elevated troponin I level on admission is associated with adverse outcome of primary angioplasty in acute myocardial infarction.  Circulation . 2000;  102 1611-1616
  • 40 Morrow D A, Antman E M, Tanasijevic M. et al . Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI 11B substudy.  J Am Coll Cardiol . 2000;  36 1812-1817
  • 41 Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group.  J Am Coll Cardiol . 1997;  29 43-48
  • 42 Newby L K, Ohman E M, Christenson R H. et al . Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin T-positive status: the paragon-B troponin T substudy.  Circulation . 2001;  103 2891-2896
  • 43 Januzzi J L, Chae C U, Sabatine M S, Jang I K. Elevation in serum troponin I predicts the benefit of tirofiban.  J Thromb Thrombolysis . 2001;  11 211-215
  • 44 FRISC II Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study.  Lancet . 1999;  354 708-715
  • 45 Akkerhuis K M, Alexander J H, Tardiff B E. et al . Minor myocardial damage and prognosis: are spontaneous and percutaneous coronary intervention-related events different?.  Circulation . 2002;  105 554-556
  • 46 Abdelmeguid A E, Topol E J, Whitlow P L, Sapp S K, Ellis S G. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions.  Circulation . 1996;  94 1528-1536
  • 47 Shyu K G, Kuan P L, Cheng J J, Hung C R. Cardiac troponin T, creatine kinase, and its isoform release after successful percutaneous transluminal coronary angioplasty with or without stenting.  Am Heart J . 1998;  135(5 Pt 1) 862-867
  • 48 Fuchs S, Gruberg L, Singh S. et al . Prognostic value of cardiac troponin I re-elevation following percutaneous coronary intervention in high-risk patients with acute coronary syndromes.  Am J Cardiol . 2001;  88 129-133
  • 49 Bertinchant J P, Polge A, Ledermann B. et al . Relation of minor cardiac troponin I elevation to late cardiac events after uncomplicated elective successful percutaneous transluminal coronary angioplasty for angina pectoris.  Am J Cardiol . 1999;  84 51-57
  • 50 Bonz A W, Lengenfelder B, Strotmann J. et al . Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).  J Am Coll Cardiol . 2002;  40 662-668
  • 51 Cantor W J, Newby L K, Christenson R H. et al . Prognostic significance of elevated troponin I after percutaneous coronary intervention.  J Am Coll Cardiol . 2002;  39 1738-1744
  • 52 Wu A H, Boden W E, McKay R G. Long-term follow-up of patients with increased cardiac troponin concentrations following percutaneous coronary intervention.  Am J Cardiol . 2002;  89 1300-1302
  • 53 Jaffe A S. Elevations in cardiac troponin measurements: false false positives.  Cardiovasc Toxicol . 2001;  1 87-92
  • 54 Mair J, Wohlfarter T, Koller A, Mayr M, Artner-Dworzak E, Puschendorf B. Serum cardiac troponin T after extraordinary endurance exercise.  Lancet . 1992;  340 1048
  • 55 Fitzmaurice T F, Brown C, Rifai N, Wu A H, Yeo K T. False increase of cardiac troponin I with heterophilic antibodies.  Clin Chem . 1998;  44 2212-2214
  • 56 Ricchiuti V, Voss E M, Ney A, Odland M, Anderson P A, Apple F S. Cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second generation cardiac troponin T assay by Boehringer Mannheim.  Clin Chem . 1998;  44 1919-1924
  • 57 Morrow D A. Cardiac-specific troponins-beyond ischemic heart disease. In: Wu AH, ed. Cardiac Markers Totowa, NJ: Humana Press; 2003: 149-170
  • 58 Giannitsis E, Muller-Bardorff M, Kurowski V. et al . Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism.  Circulation . 2000;  102 211-217
  • 59 Salim A, Velmahos G C, Jindal A. et al . Clinically significant blunt cardiac trauma: role of serum troponin levels combined with electrocardiographic findings.  J Trauma . 2001;  50 237-243
  • 60 Adams III E J, Davila-Roman V G, Bessey P Q, Blake D P, Ladenson J H, Jaffe A S. Improved detection of cardiac contusion with cardiac troponin I.  Am Heart J . 1996;  131 308-312
  • 61 Apple F S, Murakami M M, Pearce L A, Herzog C A. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease.  Circulation . 2002;  106 2941-2945
  • 62 Freda B J, Tang W H, Van Lente F, Peacock W F, Francis G S. Cardiac troponins in renal insufficiency: review and clinical implications.  J Am Coll Cardiol . 2002;  40 2065-2071
  • 63 Aviles R J, Askari A T, Lindahl B. et al . Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.  N Engl J Med . 2002;  346 2047-2052
  • 64 Apple F S, Ricchiuti V, Voss E M, Anderson P A, Ney A, Odland M. Expression of cardiac troponin T isoforms in skeletal muscle of renal disease patients will not cause false-positive serum results by the second generation cardiac troponin T assay.  Eur Heart J . 1998;  19 (suppl N) N30-N33
  • 65 Missov E, Mair J. A novel biochemical approach to congestive heart failure: cardiac troponin T.  Am Heart J . 1999;  138 95-99
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