AMEI's Current Trends in Diagnosis & Treatment

Register      Login

VOLUME 1 , ISSUE 2 ( July-December, 2017 ) > List of Articles

REVIEW ARTICLE

Cardiac Biomarkers in Acute Coronary Syndrome

Gurinder Mohan, Ranjeet Kaur, Trimaan Singh

Keywords : Acute myocardial infarction, Cardiac biomarkers, Cardiac troponin,Acute coronary syndrome

Citation Information : Mohan G, Kaur R, Singh T. Cardiac Biomarkers in Acute Coronary Syndrome. Curr Trends Diagn Treat 2017; 1 (2):80-88.

DOI: 10.5005/jp-journals-10055-0019

License: CC BY-NC 4.0

Published Online: 00-12-2017

Copyright Statement:  Copyright © 2017; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Acute coronary syndrome (ACS) is one of the leading causes of admission to the emergency departments (EDs) worldwide. The diagnosis of ACS involves the evaluation of clinical signs and symptoms, electrocardiographic assessment, and measurement of cardiac circulating biomarkers. In the last 60 years, the use of laboratory markers has changed considerably. Early biomarker assessment has entailed testing for total enzyme activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) but was highly nonspecific. Soon thereafter, the development of immunoassays, as well as technical advances in automation, allowed the measurements of the CK MB isoenzyme (CK-MB) in mass rather than in activity and myoglobin. Currently, cardiac troponins (CTn) have the highest sensitivity and specificity for myocardial necrosis and represent the biochemical gold standard for diagnosing acute myocardial infarction (AMI). This review provides a chronology of the major events that marked the evolution of cardiac biomarker testing and the development of the relative assays from the first introduction of AST in the 1950s to the last high-sensitivity troponin immunoassays in the 2010s.


PDF Share
  1. Selker HP, Zalenski RJ, Antman EM, Aufderheide TP, Bernard SA, Bonow RO, Gibler WB, Hagen MD, Johnson P, Lau J, et al. An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: a report from a National Heart Attack Alert Program Working Group. Ann Emerg Med 1997 Jan; 29(1):13-87.
  2. Singh TP, Nigam AK, Gupta AK, Singh B. Cardiac biomarkers: when to test? – Physician perspective. J Indian Acad Clin Med 2011;12(2):117-121.
  3. Alpert JS, Thygesen K, Antman E, Bassand JP. 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 Sep;36(3):959-969.
  4. Fox KA, Eagle KA, Gore JM, Steg PG, Anderson FA; GRACE and GRACE2 Investigators. The Global Registry of Acute Coronary Events, 1999 to 2009-GRACE. Heart 2010 Jul;96(14):1095-1101.
  5. Ajay VS, Prabhakaran D. Coronary heart disease in Indians: implications of the INTERHEART study. Indian J Med Res 2010 Nov;132:561-566.
  6. Morrow DA, Braunwald E. Future of biomarkers in acute coronary syndromes: moving toward a multimarker strategy. Circulation 2003 Jul;108(3):250-252.
  7. Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol 2006 Jul;48(1):1.
  8. Penttila K, Koukkunen H, Halinen M, Rantanen T, Pyorala K, Punnonen K, Penttila I. Myoglobin, creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain. Clin Biochem 2002 Nov;35(8):647.
  9. Morrow DA, Antman EM. Evaluation of highly. sensitive assays for cardiac troponin. Clin Chem 2009 Jan;55(1): 53-55.
  10. Angurana DK, Lone NA, Khan KA, Jalal S, Sangral R, Rather HA, Alai MS, Habib K, Bhogal BN, Jan VM. Rapid measurement of B- type natriuretic peptide in the diagnosis of congestive heart failure in patients presenting to the emergency department with acute shortness of breath. Int J Med Sci 2011 Mar;3(3):77-82.
  11. Ladue JS, Wr.blewski F, Karmen A. Serum glutamic oxaloacetic transaminase activity in human acute transmural myocardial infarction. Science 1954 Sep;120(3117):497-499.
  12. Karmen A, Wroblewski F, LaDue JS. Transaminase activity in human blood. J Clin Invest 1955 Jan;34(1):126-131.
  13. Penttila I, Penttila K, Rantanen T. Laboratory diagnosis of patients with acute chest pain. Clin Chem Lab Med 2000 Mar;38(3):187-197.
  14. Johnston CC, Bolton EC. Cardiac enzymes. Ann Emerg Med 1982 Jan;11(1):27-35.
  15. Wroblewski F, Ross C, Gregory K. Isoenzymes and myocardial infarction. N Engl J Med 1960 Sep;263:531-536.
  16. Konttinen A. Hydroxybutyrate dehydrogenase in detection of myocardial infarction. Lancet 1961 Sep;2(7201):556-558.
  17. Galbraith LV, Leung FY, Jablonsky G, Henderson AR. Time related changes in the diagnostic utility of total lactate dehydrogenase, lactate dehydrogenase isoenzyme-1, and two lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction. Clin Chem 1990 Jul;36(7):1317-1322.
  18. Hill BR, Levi C. Elevation of a serum component in neoplastic disease. Cancer Res 1954 Aug;14(7):513-515.
  19. Wroblewski F, LaDue JS. Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 1955 Oct;90(1):210-213.
  20. Wroblewski F, Ruegsegger P, LaDue JS. Serum lactic dehydrogenase activity in acute transmural myocardial infarction. Science 1956 Jun;123(3208):1122-1123.
  21. Ulmer DD, Vallee BL, Wacker WE. Metalloenzymes and myocardial infarction. II. Malic and lactic dehydrogenase activities and zinc concentrations in serum. N Engl J Med 1956 Sep;255(10):450-456.
  22. Dreyfus JC, Schapira G, Rasnais J, Scebat L. Serum creatine kinase in the diagnosis of myocardial infarct. Rev Fr Etud Clin Biol 1960 Apr;5:386-387.
  23. Sorensen NS. Creatine phosphokinase in the diagnosis of myocardial infarction. Acta Med Scand 1963 Jan/Dec;174(6): 725-734.
  24. Shell WE, Kjekshus JK, Sobel BE. Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity. J Clin Invest 1971 Dec;50(12):2614-2625.
  25. Sobel BE, Bresnahan GF, Shell WE, Yoder RD. Estimation of infarct size in man and its relation to prognosis. Circulation 1972 Oct;46(4):640-648.
  26. Roe CR, Limbird LE, Wagner GS, Nerenberg ST. Combined isoenzyme analysis in the diagnosis of myocardial injury: Application of electrophoretic methods for the detection and quantitation of the creatine phosphokinase MB isoenzyme. J Lab Clin Med 1972 Oct;80(4):577-590.
  27. Panteghini M. Enzyme and muscle diseases. Curr Opin Rheumatol 1995;7:469-474.
  28. Puleo PR, Guadagno PA, Roberts R, Scheel MV, Marian AJ, Churchill D, Perryman MB. Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB. Circulation 1990 Sep;82(3):759-764.
  29. Wu AH, Wang XM, Gornet TG, Ordóñez-Llanos J. Creatine kinase MB isoforms in patients with skeletal muscle injury: ramifications for early detection of acute myocardial infarction. Clin Chem 1992 Dec;38(12):2396-2400.
  30. Zimmerman J, From R, Meyer D, Boudreaux A, Wun CC, Smalling R, Davis B, Habib G, Roberts R. Diagnostic marker cooperative study for the diagnosis of myocardial infarction. Circulation 1999 Apr;99(13):1671-1677.
  31. Seo H, Miyazaki S, Furuno T, Nonogi H, Haze K, Hiramori K. Creatine kinase-MB protein mass is a better indicator for the assessment of acute myocardial infarction in the lower range of creatine kinase level. Jpn Heart J 1993 Nov;34(6): 717-727.
  32. Pettersson T, Ohlsson O, Tryding N. Increased CK-MB (mass concentration) in patients without traditional evidence of acute myocardial infarction. A risk indicator of coronary death. Eur Heart J 1992 Oct;13(10):1387-1392.
  33. Ravkilde J, Nissen H, Mickley H, Andersen PE, Thayssen P, Horder M. Cardiac troponin-T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris. Am Heart J 1994;127: 13-20.
  34. Abbas SA, Glazier JJ, Wu AH, Dupont C, Green SF, Pearsall LA, Waters DD, McKay RG. Factors associated with the release of cardiac troponin T following percutaneous transluminal coronary angioplasty. Clin Cardiol 1996 Oct;19(10):782-786.
  35. Pearson JR, Carrea F. Evaluation of the clinical usefulness of a chemiluminometric method for measuring creatine kinase. Clin Chem 1990.;36:1809.
  36. Gilkeson G, Stone MJ, Waterman M, Ting R, Gomez-Sanchez CE, Hull A, Willerson JT. Detection of myoglobin by radioimmunoassay in human sera: its usefulness and limitations as an emergency room screening test for acute myocardial infarction. Am Heart J 1978 Jan;95(1):70-77.
  37. Varki AP, Roby DS, Watts H, Zatuchni J. Serum myoglobin in acute myocardial infarction: a clinical study and review of the literature. Am Heart J 1978 Nov;96(5):680-688.
  38. Bhayana V, Cohoe S, Leung FY, Jablonsky G, Henderson AR. Diagnostic evaluation of creatine kinase-2 mass and creatine kinase-3 and -2 isoform ratios in early diagnosis of acute myocardial infarction. Clin Chem 1993;39:488-495.
  39. Greaser ML, Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem 1971;246: 4226-4233.
  40. Katus HA, Remppis A, Looser S, Hallermeier K, Scheffold T, Kübler W. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol 1989 Dec;21(12):1349-1353.
  41. Horwich TB, Patel J, MacLellan WR, Fonarow GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003 Aug 19;108(7):833-838.
  42. Ni CY. Cardiac troponin I: a biomarker for detection and risk stratification of minor myocardial damage. Clin Lab 2001; 47(9-10):483-492.
  43. Ohman EM, Armstrong PW, Christenson RH, Granger CB, Katus HA, Hamm CW, O'Hanesian MA, Wagner GS, Kleiman NS, Harrell FE Jr, et al. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators. N Engl J Med 1996 Oct 31;335(18):1333-1341.
  44. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002 Dec 3;106(23): 2941-2945.
  45. Evaluation of a bedside whole-blood rapid troponin T assay in the emergency department. Rapid Evaluation by Assay of Cardiac Troponin T (REACTT) Investigators Study Group. Acad Emerg Med 1997 Nov;4(11):1018-1024.
  46. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997 Dec 4;337(23):1648-1653.
  47. Li D, Jialal I, Keffer J. Greater frequency of increased cardiac troponin T than increased cardiac troponin I in patients with chronic renal failure. Clin Chem 1996 Jan;42(1):114-115.
  48. Needham DM, Shufelt KA, Tomlinson G, Scholey JW, Newton GE. Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature. Can J Cardiol 2004 Oct;20(12):1212-1218.
  49. Khan NA, Hemmelgarn BR, Tonelli M, Thompson CR, Levin A. Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis. Circulation 2005 Nov 15;112(20):3088-3096.
  50. Jurlander B, Farhi ER, Banas JJ Jr, Keany CM, Balu D, Grande P, Ellis AK. Coronary angiographic findings and troponin T in patients with unstable angina pectoris. Am J Cardiol 2000 Apr 1;85(7):810-814.
  51. Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group. Circulation 1996 May 1;93(9):1651-1657.
  52. Stubbs P, Collinson P, Moseley D, Greenwood T, Noble M. Prospective study of the role of cardiac troponin T in patients admitted with unstable angina. BMJ 1996 Aug 3;313(7052): 262-264.
  53. Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM. Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 2002;346: 204-205.
  54. Sakuma M, Nakamura M, Tanaka F, Onoda T, Itai K, Tanno K, Ohsawa M, Sakata K, Yoshida Y, Kawamura K, et al. Plasma B-type natriuretic peptide level and cardiovascular events in chronic kidney disease in a community-based population. Circ J 2010;74(4):792-797.
  55. Sommerer C, Beimler J, Schwenger V, Heckele N, Katus HA, Giannitsis E, Zeier M. Cardiac biomarkers and survival in haemodialysis patients. Eur J Clin Invest 2007;37(5):350-356.
  56. Galvani M, Ottani F, Oltrona L, Ardissino D, Gensini GF, Maggioni AP, Mannucci PM, Mininni N, Prando MD, Tubaro M, et al. N-terminal pro-brain natriuretic peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes. Circulation 2004 Jul 13;110(2): 128-134.
  57. de Lemos JA, Morrow DA. Brain natriuretic peptide measurement in acute coronary syndromes: ready for clinical application? Circulation 2002 Dec 3;106(23):2868-2870.
  58. White HD, French JK. Use of brain natriuretic peptide levels for risk assessment in non-ST-elevation acute coronary syndromes. J Am Coll Cardiol. 2003 Dec 3;42(11):1917-1920.
  59. Varo N, de Lemos JA, Libby P, Morrow DA, Murphy SA, Nuzzo R, Gibson CM, Cannon CP, Braunwald E, Schönbeck U. Risk prediction after acute coronary syndromes. Circulation 2003 Sep 2;108(9):1049-1052.
  60. Sabatine MS, Morrow DA, de Lemos JA, Gibson CM, Murphy SA, Rifai N, McCabe C, Antman EM, Cannon CP, Braunwald E. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 2002 Apr 16;105(15):1760-1763.
  61. Lindahl B, Lindbäck J, Jernberg T, Johnston N, Stridsberg M, Venge P, Wallentin L. Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy. J Am Coll Cardiol 2005 Feb 15;45(4):533-541.
  62. Jernberg T, James S, Lindahl B, Stridsberg M, Venge P, Wallentin L. NT-proBNP in unstable coronary artery disease–experiences from the FAST, GUSTO IV and FRISC II trials. Eur J Heart Fail 2004 Mar 15;6(3):319-325.
  63. Heeschen C, Dimmeler S, Fichtlscherer S, Hamm CW, Berger J, Simoons ML, Zeiher AM, CAPTURE Investigators. Prognostic value of placental growth factor in patients with acute chest pain. JAMA 2004 Jan 28;291(4):435-441.
  64. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004 Feb 12; 350(7):655-663.
  65. Kay JD, Trichon BH, Kisslo M, Pentagini M. Serum brain natriuretic peptide levels cannot differentiate pulmonary disease from left-heart failure if the right ventricle is dilated. Circulation 2003;108 IV:397.
  66. Kikuta K, Yasue H, Yoshimura M, Morita E, Sumida H, Kato H, Kugiyama K, Ogawa H, Okumura K, Ogawa Y, et al. Increased plasma levels of B-type natriuretic peptide in patients with unstable angina. Am Heart J 1996 Jul;132(1 Pt 1):101-107.
  67. Tateishi J, Masutani M, Ohyanagi M, Iwasaki T. Transient increase in plasma brain (B-type) natriuretic peptide after percutaneous transluminal coronary angioplasty. Clin Cardiol. 2000 Oct;23(10):776-780.
  68. Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, Heineke J, Kotlarz D, Xu J, Molkentin JD, et al. The transforming growth factor – Beta superfamily member growth – differentiationfactor – 15 protects the heart from ischemia. Circ Res 2006;98(3):351-360.
  69. Glatz JF, van Bilsen M, Paulussen RJ, Veerkamp JH, van der Vusse GJ, Reneman RS. Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox. Biochim Biophys Acta 1988 Jul 1;961(1):148-152.
  70. Ishii J, Wang JH, Naruse H, Taga S, Kinoshita M, Kurokawa H, Iwase M, Kondo T, Nomura M, Nagamura Y, et al. Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid-binding protein in early detection of acute myocardial infarction. Clin Chem 1997 Aug;43(8 Pt 1):1372-1378.
  71. Alhadi HA, Fox KA. Do we need additional markers of myocyte necrosis: the potential value of heart fatty-acidbinding protein. QJM 2004 Apr;97(4):187-198.
  72. Glatz JF, Van der Vusse GJ, Maessen JG, Van Dieijen-Visser MP, Hermens WT. Fatty acid-binding protein as marker of muscle injury: experimental findings and clinical application. Acta Anaesthesiol Scand Suppl 1997;111:292-294.
  73. Górski J, Hermens WT, Borawski J, Mysliwiec M, Glatz JF. Increased fatty acid-binding protein concentration in plasma of patients with chronic renal failure. Clin Chem 1997 Jan;43(1): 193-195.
  74. Al-Hadi HA, William B, Fox KA. Serum level of heart-type Fatty Acid-binding protein in patients with chronic renal failure. Sultan Qaboos Univ Med J 2009 Dec;9(3):311-314.
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.