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Emerging Biomarkers of Myocardial Ischemia

  • Jesse E. Adams
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Myocardial ischemia has a complex pathophysiology and can manifest with a multitude of clinical presentations, including without symptoms. Patients who present to the emergency department with a complaint of chest pain therefore require substantial diagnostic effort to determine whether their symptoms are related to acute myocardial ischemia. Present diagnostic approaches are typically protocol driven and include serial electrocardiograms and biomarkers obtained over an 8- to 12-h period for the detection of myocardial necrosis. This paradigm is reasonably effective in identifying patients who have acute coronary syndrome, especially when there is associated myocardial necrosis, but it offers only modest sensitivity and relies heavily on biomarkers that are increased only in the presence of irreversible myocardial injury (i.e., necrosis). For this reason, there has been intense research and clinical interest in the development of sensitive biomarkers of myocardial ischemia that are not dependent on the presence of myocardial necrosis. Markers investigated for this purpose include ultrasensitive troponin, ischemi-modified albumin, sCD40L, myeloperoxidase, glutathione peroxidase, nourins, unbound free fatty acid, and whole-blood choline. Despite the emergence of these candidate markers of ischemia, currently there is not sufficient evidence to recommend widespread adoption of any of them into clinical practice.

Key Words

Ischemia unstable angina biomarkers myocardial infarction prognosis 

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References

  1. 1.
    Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation 2000;102:118–122.PubMedGoogle Scholar
  2. 2.
    Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction: 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 2000;36:970–1062.CrossRefPubMedGoogle Scholar
  3. 3.
    Pope JH, Selker HP. Diagnosis of acute cardiac ischemia. Emerg Med Clin North Am 2003;21:27–59.CrossRefPubMedGoogle Scholar
  4. 4.
    Selker HP, Zalenski RJ, Antman EM, 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;29:13–87.CrossRefPubMedGoogle Scholar
  5. 5.
    Gerstenblith G. Derangements in cardiac metabolism in the ischemic state and consequences of reperfusion. Adv Stud Med 2004;4(6B):S464–S471.Google Scholar
  6. 6.
    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;36:959–969.CrossRefPubMedGoogle Scholar
  7. 7.
    Jaffe AS. Testing the wrong hypothesis: the failure to recognize the limitations of troponin testing. J Am Coll Cardiol 2001;38:999–1001.CrossRefPubMedGoogle Scholar
  8. 8.
    McDonough JL, Labugger R, Van Eyk JE. Prepare to meet your markers: making the most of troponin degradation. In: Adams JE, Apple FS, Jaffe AS, Wu AHB, eds. Markers in Cardiology: Current and Future Clinical Applications. Futura, Armonk, NJ, 2001, pp. 13–21.Google Scholar
  9. 9.
    Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135–1143.CrossRefPubMedGoogle Scholar
  10. 10.
    Liuzzo G, Biasucci LM, Rebuzzi AG, et al. Plasma protein acute-phase response in unstable angina is not induced by ischemic injury. Circulation 1996;94:2373–2380.PubMedGoogle Scholar
  11. 11.
    Morrow DA, Rifai N, Antman EM, et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. J Am Coll Cardiol 1998;31:1460–1465.CrossRefPubMedGoogle Scholar
  12. 12.
    Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR. Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation 2002;106:896–899.CrossRefPubMedGoogle Scholar
  13. 13.
    Inwald DP, McDowell A, Peters MI, et al. CD40 is constitutively expressed on platelets and prvodes a novel mechanism for platelet activation. Circ Res 2003;92:1041–1048.CrossRefPubMedGoogle Scholar
  14. 14.
    Heeschen C, Dimmler S, Hamm CW, et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003;348:1104–1111.CrossRefPubMedGoogle Scholar
  15. 15.
    Varo N, de Lemos JA, Libby P, et al. Soluble CD40L risk prediction after acute coronary syndromes. Circulation 2003;108:1049–1052.CrossRefPubMedGoogle Scholar
  16. 16.
    Baldus S, Heitzer T, Eiserich JP, et al. Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. Free Radic Biol Med 2004;37:902–911.CrossRefPubMedGoogle Scholar
  17. 17.
    Baldus S, Heeschen C, Meinertz T, et al., for the CAPTURE investigators. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 2003;108:1440–1445.CrossRefPubMedGoogle Scholar
  18. 18.
    Brennan ML, Penn MS, Van Lente F, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003;349:1595–1604.CrossRefPubMedGoogle Scholar
  19. 19.
    Qin QP, Laitinen P, Majamaa-Voltti K, et al. Release patterns of pregnancy associated plasma protein A (PAPP-A) in patients with acute coronary syndromes. Scand Cardiovasc J 2002;36:358–361.CrossRefPubMedGoogle Scholar
  20. 20.
    Cosin-Sales J, Christiansen M, Kaminski P, et al. Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP) are related to complex stenosis morphology in patients with stable angina pectoris. Circulation 2004;109:1724–1728.CrossRefPubMedGoogle Scholar
  21. 21.
    Lund J, Qin QP, Ilva T, et al. Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation. Circulation 2003;108:1924–1926.CrossRefPubMedGoogle Scholar
  22. 22.
    Laterza OF, Cameron SJ, Chappell D, Sokoll LJ, Green GB. Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients. Clin Chim Acta 2004;348:163–169.CrossRefPubMedGoogle Scholar
  23. 23.
    Chiang TM. Activation of phospholipase D in human platelets by collagen and thrombin and its relationship to platelet aggregation. Biochem Biophys Acta 1994;1224:147–155.CrossRefPubMedGoogle Scholar
  24. 24.
    Cox DA, Cohen ML. Relationship between phospholipase D activation and endothelial vasomotor dysfunction in rabbit aorta. J Pharmacol Exp Ther 1997;283:305–311.PubMedGoogle Scholar
  25. 25.
    Wevers RA, Engelke U, Heerschap A. High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies. Clin Chem 1994;40:1245–1250.PubMedGoogle Scholar
  26. 26.
    Danne O, Mockel M, Lueders C, et al. Prognostic implications of elevated whole blood choline levels in acute coronary syndromes. Am J Cardiol 2003;91:1060–1067.CrossRefPubMedGoogle Scholar
  27. 27.
    Bar-Or D, Lau E, Rao N, Winkler J. A novel assay for the cobalt-albumin binding and its potential as a marker for myocardial ischemia: a preliminary report. J Emerg Med 2000;19:311–315.CrossRefPubMedGoogle Scholar
  28. 28.
    Bar-Or D, Winkler J, VanBenthuysen K, et al. Reduced cobalt binding of human albumin with ransient myocardial ischemia following elective percutaneous transluminal coronary angioplasty compared to CKMB, myoglobin and troponin I. Am Heart J 2001;141:985–991.CrossRefPubMedGoogle Scholar
  29. 29.
    Christenson RH, Duh SH, Sanhai WR, et al. Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 2001;47:464–470.PubMedGoogle Scholar
  30. 30.
    Sinha MK, Gaze DC, Tippins JR, Collinson PO, Kaski JC. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Circulation 2003;107:2403–2405.CrossRefPubMedGoogle Scholar
  31. 31.
    Sinha MK, Roy D, Gaze DC, et al. Role of “asischemia modified albumin,” a new biochemical marker of myocardial ischemia, in the early diagnosis of acute coronary artery syndromes. Emerg Med J 2004;21:29–34.CrossRefPubMedGoogle Scholar
  32. 32.
    Simic D, Mimic-Oka J, Pljesa M, et al. Time course of erythrocyte antioxidant activity in patients treated by thrombolysis for acute myocardial infarction. Jpn Heart J 2003;2003:823–832.CrossRefGoogle Scholar
  33. 33.
    Blankenberg S, Rupprecht HJ, Bickel C, et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003;349:1605–1613.CrossRefPubMedGoogle Scholar
  34. 34.
    Kleinfeld AM, Prothro D, Brown DL, et al. Increases in serum unbound free fatty acid levels following coronary angioplasty. Am J Cardiol 1996;78:1350–1354.CrossRefPubMedGoogle Scholar
  35. 35.
    Kleinfeld AM, Kleinfeld KJ, Adams JE. Serum levels of unbound free fatty acids reveal high sensitivity for early detection of acute myocardial infarction in patient samples from the TIMI II trial. J Am Coll Cardiol 2002;39(Suppl 2):413A.Google Scholar
  36. 36.
    Adams JE, Kleinfeld A, Roe M, et al. Measurement of levels of unbound free fatty acid allows the early identification of patients with acute coronary syndromes [abstract]. Circulation 2002;105:1–324.CrossRefGoogle Scholar
  37. 37.
    Elgebaly SA, Kozol RA, Masetti P, Bohr M, Lennan C. Release of neutrophil chemotactic factors from ischemic myocardial tissues. Surg Forum 1987;38:276–279.Google Scholar
  38. 38.
    Elgebaly SA, Hashimi FH, et al. Cardiac-derived neutrophil chemotactic factors: detection in coronary sinus effluents of patients undergoing myocardial revascularization. J Thorac Cardiovasc Surg 1992;103:952–959.PubMedGoogle Scholar
  39. 39.
    Elgebaly SA, Mauri F, Azrin M, et al. Cardiac-derived neutrophil chemotactic factor: an early diagnostic marker for cardiac patients. 2004; manuscript in preparation.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Jesse E. Adams
    • 1
  1. 1.Medical Center CardiologistsJewish Hospital Heart and Lung InstituteLouisville

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