Pathogenesis of the Acute Coronary Syndromes: Hypotheses Generated from Clinical Experience

  • Narinder P. Bhalla
  • John A. Ambrose
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)


The acute coronary syndromes include unstable angina, myocardial infarction (both non-Q-wave and Q-wave), and sudden ischemic death. Common to all these syndromes, in a majority of cases, is the event of plaque disruption. Thrombus generated as a result of plaque disruption is clinically manifested as one of the acute coronary syndromes. Hence, there is considerable overlap amongst the syndromes, and the distinction may simply be the amount of thrombus generated and the presence of collateral circulation. Though many theories have been advanced to elucidate the events leading to plaque rupture, the temporal determinants of the final event remain a mystery, In this chapter we discuss the various hypotheses regarding the events of plaque rupture, the clinical data regarding the acute coronary syndromes, and how these relate to our current understanding of the pathogenesis of the acute coronary syndromes.


Acute Coronary Syndrome Acute Myocardial Infarction Unstable Angina Plaque Rupture Ulceration Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Berenson G. Epidemiology and prevention. ACCSAP 1995 1.3.Google Scholar
  2. 2.
    Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 92:657, 1995.PubMedGoogle Scholar
  3. 3.
    Ambrose JA. Coronary angiographic findings in the acute coronary syndromes, in Bleifeld W, Braunwald WE, Hamm C (eds). Unstable Angina. Berlin/Heidelberg: Springer Verlag, 1990:112.Google Scholar
  4. 4.
    Fox B, James K, Morgan B, Seed A. Distribution of fatty and fibrous plaques in young human coronary arteries. Arteriosclerosis 48:139, 1983.Google Scholar
  5. 5.
    Kjaernes M, Svindland A, Walloe L, Willie SO. Location of early atherosclerotic lesions in an arterial bifurcation in humans. Acta Pathol Microbiol Immunol Second Sect 89:35, 1981.Google Scholar
  6. 6.
    Zairns CK, Giddens DP, Bhardavaj BK, et al. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque locationwith flow velocity profiles and wall shear stress. Circ Res 53:502, 1983.Google Scholar
  7. 7.
    Fuster V. Pathogenesis of atherosclerosis. In Spittell JA Jr (ed). Clinical Medicine. Philadelphia: Harper & Row 1981:1.Google Scholar
  8. 8.
    Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. Circulation 92:1355, 1995.PubMedGoogle Scholar
  9. 9.
    Stary HC, Chandler AB, Glagov S, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. Arterioscler Thromb 14:840, 1994.PubMedGoogle Scholar
  10. 10.
    Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371, 1987.PubMedCrossRefGoogle Scholar
  11. 11.
    Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 9(Suppl. 1):119, 1989.Google Scholar
  12. 12.
    Fuster V, Kottke BA. Atherosclerosis. A. Pathogenesis, pathology, and presentation of atherosclerosis. In Brandenburg RO (ed). Cardiology: Fundamentals and Practice. Year Book Medical, 1987:951.Google Scholar
  13. 13.
    Ross R. The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488, 1986.PubMedCrossRefGoogle Scholar
  14. 14.
    Chapman I. Morphogenesis of occluding coronary artery thrombosis. Arch Pathol 80:256, 1965.PubMedGoogle Scholar
  15. 15.
    Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 12:56, 1988.PubMedGoogle Scholar
  16. 16.
    Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild to moderate coronary artery disease? Circulation 78:1157, 1988.PubMedGoogle Scholar
  17. 17.
    Giroud D, Li JM, Urban P, et al. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 69:729, 1993.Google Scholar
  18. 18.
    Nobuyoshi M, Tanaka M, Nosaka H, et al. Progression of coronary atherosclerosis: Is coronary spasm related to progression? J Am Coll Cardiol 18:904, 1991.PubMedGoogle Scholar
  19. 19.
    Alderman EL, Corley SD, Fisher LD, et al. Five year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). J Am Coll Cardiol 22:1141, 1993.PubMedGoogle Scholar
  20. 20.
    Falk E. Morphologic features of unstable atherthrombotic plaques underlying acute coronary syndromes. Am J Cardiol 63(Suppl. E):114E, 1989.PubMedGoogle Scholar
  21. 21.
    Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial athersclerotic plaques. Am J Cardiol 66:1368, 1990.PubMedGoogle Scholar
  22. 22.
    Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 69:377, 1993.PubMedGoogle Scholar
  23. 23.
    Lundberg B. Chemical composition and physical state of lipid deposits in ahterosclerosis. Athersclerosis 56:93, 1985.Google Scholar
  24. 24.
    Small DM. Progression and regression of atherosclerotic lesions: Insights from lipid physical biochemistry. Arteriosclerosis 8:103, 1988.PubMedGoogle Scholar
  25. 25.
    Wagner WD, St Clair RW, Clarkson TB, Connor JR. A study of atherosclerosis regression in Macaca mulatta, III: Chemical changes in arteries from animals with atherosclerosis induced for 19 months and regressed for 48 months at plasma cholesterol levels of 300 or 200mg/dl. Am J Pathol 100:633, 1980.PubMedGoogle Scholar
  26. 26.
    Loree HM, Tobias BJ, Gibson LJ, et al. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thrmob 14:230, 1994.Google Scholar
  27. 27.
    Buchwald H, Vargo RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypcrcholesterolemia: Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 323:946, 1990.PubMedCrossRefGoogle Scholar
  28. 28.
    Watts GF, Lewis B, Brunt JNH, et al. Effects on coronary artery disease of lipid lowering diet plus cholestyramine, in the St Thomas’ Athersclerosis Regression Study (STARS). Lancet 339:563, 1992.PubMedGoogle Scholar
  29. 29.
    Blankenhorn DH, Azen SP, Dieter KM, et al. Coronary angiographie changes with Lovastatin therapy: The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 119:969, 1993.PubMedGoogle Scholar
  30. 30.
    Scandanavian Simvastatin Survival Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandanavian Simvastatin Survival Study (4S). Lancet 344:1383, 1994.Google Scholar
  31. 31.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with ptavastatin in men with hypercholesterolemia. N Engl J Med 333:1301, 1995.PubMedGoogle Scholar
  32. 32.
    Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 323:1289, 1990.PubMedCrossRefGoogle Scholar
  33. 33.
    Burleigh MC, Briggs AD, Lendon CL, et al. Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: Span-wise variations. Atherosclerosis 96:71, 1992.PubMedGoogle Scholar
  34. 34.
    Libby P. Molecular bases of the acute coronary syndromes. Circulation 91:2844, 1995.PubMedGoogle Scholar
  35. 35.
    Amento E.P, Palmer H, Libby P. Cytokines positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb 11:1223, 1991.PubMedGoogle Scholar
  36. 36.
    Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 2:941, 1989.PubMedGoogle Scholar
  37. 37.
    van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimai rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89:36, 1994.PubMedGoogle Scholar
  38. 38.
    Moreno PR, Falk E, Palacios IF, et al. Macrophage infiltration in acute coronary syndromes: Implications for plaque rupture. Circulation 90:775, 1994.PubMedGoogle Scholar
  39. 39.
    Shah PK, Falk E, Badimon JJ, et al. Human monocyce-derived macrophages express collagenase and induce collagen breakdown in atherosclerotic fibrous caps: Implications for plaque rupture (abstr). Circulation 88(Suppl. I):1–254, 1993.Google Scholar
  40. 40.
    Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: Potential role of matrix degrading metalloproteinases and implications for plaque rupture. Circulation 92:1565, 1995.PubMedGoogle Scholar
  41. 41.
    Henney AM, Wakeley PR, Davies MJ, et al. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridizarion. Proc Natl Acad Sci USA 88:8154, 1991.PubMedGoogle Scholar
  42. 42.
    Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix-metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 94:2493, 1994.PubMedGoogle Scholar
  43. 43.
    Brown DL, Hibbs MS, Kearny M, et al. Identification of 92-kD gelatinase in human coronary atherosclerotic lesions: Association of active enzyme synthesis with unstable angina. Circulation 91:2125, 1995.PubMedGoogle Scholar
  44. 44.
    Neri Serneri GG, Gensini GF, Poggesi L, et al. The role of extraplatelet thromboxane A2 in unstable angina investigated with a dual thromboxane A2, inhibitor: Importance of activated monocytes. Cor Art Dis 5:137, 1994.Google Scholar
  45. 45.
    Kaartinen M, Penttilä A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 90:1669, 1994.PubMedGoogle Scholar
  46. 46.
    Gruber BL, Marchese MJ, Suzuki K, et al. Synovial procollagenase activation by human mast cell tryptase: Dependence upon matrix metalloptoteinase 3 activation. J Clin Invest 84: 1657, 1989.PubMedCrossRefGoogle Scholar
  47. 47.
    Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121, 1990.PubMedGoogle Scholar
  48. 48.
    Shapiro SD, Campbell EJ, Kobayashi DK, Welgus HG. Immune modulation of metalloproteinase production in human macrophages: Selective pretranslational suppression of interstial collagenase and stromelysin biosynthesis by interferon-γ. J Clin Invest 86:1204, 1990.PubMedGoogle Scholar
  49. 49.
    Saarinen J, Kalkkinen N, Welgus HG, Kovanen PT. Activation of human interstitial procollagenase through direct cleavage of the Leu83 Thr84 bond by mast cell chymase. J Biol Chem 269:181340, 1994.Google Scholar
  50. 50.
    Cheng GC, Loree HM, Kamm RD, et al. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: A structural analysis with histopathological correlation. Circulation 87:1179, 1993.PubMedGoogle Scholar
  51. 51.
    Loree HM, Kamm RD, Stringfellow RG, Lee RT. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res 71:850, 1992.PubMedGoogle Scholar
  52. 52.
    Maclsaac AI, Thomas JD, Topol EJ. Toward the quiescent coronary plaque. J Am Coll Curdiol 22:1228, 1993.Google Scholar
  53. 53.
    Fitzgerald JD. By what means might beta blockers prolong life after acute myocardial infarction? Eur Heart J 8:945, 1987.PubMedGoogle Scholar
  54. 54.
    Neri Serneri G, Abbate R, Gori AM, et al. Transient intermittent lymphocyte activation is responsible for the instability of unstable angina. Circulation 86:790, 1992.Google Scholar
  55. 55.
    Dinerman J, Mehta J, Saldeen T, et al. Increased neutrophil elastasc in unstable angina and acute myocardial infarction. Am J Cardiol 15:1559, 1990.Google Scholar
  56. 56.
    Berk B, Weintraub W, Alexander R. Elevation of Creacrive protein in “active” coronary artery disease. Am J Cardiol 65:168, 1990.PubMedGoogle Scholar
  57. 57.
    Liuzzo A, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid “a” protein in severe unstable angina. N Engl J Med 331:417, 1994.PubMedGoogle Scholar
  58. 58.
    Mazzone A, De Servi, Ricevuti G, et al. Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 22:358, 1993.Google Scholar
  59. 59.
    Flugelman MY, Virmani R, Correa R, et al. Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina: A clue to the mechanism of transformation from stable to the unstable clinical state. Circulation 88:2493, 1993.PubMedGoogle Scholar
  60. 60.
    Roberts WC, Kragel AH, Gertz SD, Roberts CS. Coronary arteries in unstable angina pectoris, acute myocardial infarction, and sudden coronary death. Am Heart J 127:1588, 1994.PubMedGoogle Scholar
  61. 61.
    Ambrose JA. Coronary arteriographic analysis and angiographic morphology. J Am Coll Cardiol 13:1492, 1989.PubMedGoogle Scholar
  62. 62.
    Ambrose JA, Winters SL, Stern A, et al. Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 5:609, 1985.PubMedGoogle Scholar
  63. 63.
    Haft JI, Goldstein JE, Niemiera ML. Coronary arteriographic lesion of unstable angina. Chest 92:609, 1987.PubMedGoogle Scholar
  64. 64.
    Williams AE, Freeman MR, Chisolm RJ, et al. Angiographic morphology in unsrable angina pectoris. Am J Cardiol 62:1024, 1988.PubMedGoogle Scholar
  65. 65.
    Bresnahan DR, Davis DR, Holmes DR Jr, Smith HC. Angiographic occurrence and clinical correlates of intraluminal coronary artery thrombus: Role of unstable angina. J Am Coll Cardiol 6:285, 1985.PubMedGoogle Scholar
  66. 66.
    Vetrovec GW, Cowley MJ, Overton H, Richardson DW. Intracoronary thrombus in syndromes of unstable myocardial ischemia. Am Heart J 102:1202, 1981.PubMedGoogle Scholar
  67. 67.
    Capone G, Wolf NM, Meyer B, Meister SG. Frequency of intracoronary filling defects by angiography in angina pectoris at rest. Am J Cardiol 56:403, 1985.PubMedGoogle Scholar
  68. 68.
    Mandlekorn JB, Wolf NM, Singh S, et al. Intracoronary thrombus in nontransmural myocardial infarction and unstable angina pectoris. Am J Cardiol 52:1, 1983.Google Scholar
  69. 69.
    Freeman MR, Williams AE, Chisolm RJ, Armstrong PW. Intracoronary and thrombus and complex morphology in unstable angina. Relation to timing of angiography and in-hospital cardiac events. Circulation 80:17, 1989.PubMedGoogle Scholar
  70. 70.
    Plotnick GD, Greene HI, Carliner NH, et al. Clinical indicators of left main coronary artery disease in unstable angina. Ann Intern Med 91:149, 1979.PubMedGoogle Scholar
  71. 71.
    Bugiardini R, Pozzati A, Borghi A, et al. Angiographic morphology in unstable angina and its relation to transient myocardial ischemia and hospital outcome. Am J Cardiol 67:460, 1991.PubMedGoogle Scholar
  72. 72.
    Bar FW, Raynaud P, Renkin JP, et al. Coronary angiographic findings do not predict clinical outcome in patients with unstable angina. J Am Coll Cardiol 24:1453, 1994.PubMedGoogle Scholar
  73. 73.
    Merlini PA, Bauer KA, Oltrona L, et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 90:61, 1994.PubMedGoogle Scholar
  74. 74.
    Lee G, Garcia JM, Corso PJ, et al. Correlation of coronary angioscopic to angiographic findings in coronary artery disease. Am J Cardiol 58:238, 1986.PubMedGoogle Scholar
  75. 75.
    Spears JR, Spokojny AM, Marais HJ. Coronary angioscopy during cardiac catheterization. J Am Coll Cardiol 6:93, 1985.PubMedGoogle Scholar
  76. 76.
    Uchida Y, Tomaru T, Nakamura F, et al. Percutaneous coronary angioscopy in patients with ischemic heart disease. Am Heart J 114:1216, 1987.PubMedGoogle Scholar
  77. 77.
    White CJ, Ramee SR, Collins TJ, et al. Percutaneous coronary angioscopy of saphenous vein coronary bypass grafts. J Am Coll Cardiol 21:1181, 1993.PubMedGoogle Scholar
  78. 78.
    de Feyter PJ, Ozaki Y, Baptista J, et al. Ischemia related lesion characteristics in patients with stable or unstable angina: A study with intracoronary angioscopy and ultrasound. Circulation 92:1408, 1995.PubMedGoogle Scholar
  79. 79.
    Sherman TC, Litvack F, Grundfest W, et al. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 315:913, 1986.PubMedCrossRefGoogle Scholar
  80. 80.
    Mizuno K, Miyamoto A, Satomura K, et al. Angioscopic coronary macromorphology in patients with acute coronary disorders. Lancet 337:809, 1991.PubMedGoogle Scholar
  81. 81.
    Mizuno K, Satomura K, Miyamoto A, et al. Angioscopic evaluation of coronary artery thrombi in acute coronary artery syndromes. N Engl J Med 326:287, 1992.PubMedCrossRefGoogle Scholar
  82. 82.
    Kragel AH, Reddy SG, Wittes JT, Roberts WC. Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death, and acute myocardial infarction. J Am Coll Cardiol 18:801, 1991.PubMedGoogle Scholar
  83. 83.
    Silva JA, Escobar A, Tyrone J, et al. A comparison of angioscopic findings between diabetic and nondiabetic patients. Circulation 92:1731, 1995.PubMedGoogle Scholar
  84. 84.
    Fein F. Heart disease in diabetes. Cardiovasc Rev Rep 3:877, 1982.Google Scholar
  85. 85.
    Barrett-Connor E, Orchard T. Insulin dependent diabetes mellitus and ischemic heart disease. Diabetes Care 8:65, 1985.PubMedGoogle Scholar
  86. 86.
    Moise A, Theroux P, Taigmans Y, et al. Unstable angina and progression of coronary atherosclerosis. N Engl J Med 309:685, 1983.PubMedCrossRefGoogle Scholar
  87. 87.
    Ambrose JA, Winters SL, Arora RR, et al. Angiographic evolution of coronary artery morphology in unstable angina. J Am Coll Cardiol 7:472, 1986.PubMedGoogle Scholar
  88. 88.
    Chen L, Chester MR, Redwood S, et al. Angiographic stenosis progression and coronary events in patients with “stabilized” unstable angina. Circulation 91:2319, 1995.PubMedGoogle Scholar
  89. 89.
    Ambrose JA, Hjemdahl-Monsen C, Borrico S, et al. Quantitative and qualitative effects of intracoronary steptokinase in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol 9:1156, 1987.PubMedGoogle Scholar
  90. 90.
    Topol EJ, Nicklas JM, Kander NH, et al. Coronary revascularization after intravenous tissue plasminogen activator for unstable angina pectoris: Results of a randomized, double blind, placebo controlled trial. Am J Cardiol 62:368, 1988.PubMedGoogle Scholar
  91. 91.
    DeZwaan C, Bar FW, Janssen JHA, et al. Effects of thrombolytic therapy in unstable angina: Clinical and angiographic results. J Am Coll Cardiol 12:301, 1988.Google Scholar
  92. 92.
    Gold HK, Johns JA, Leinbach RC, et al. A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in patients with unstable angina pectoris. Circulation 75:1192, 1987.PubMedGoogle Scholar
  93. 93.
    Vetrovec GW, Leinbach RC, Gold UK, Cowley MJ. Intracoronary thrombolysis in syndromes of unstable ischemia: Angiographie and clinical results. Am Heart J 104:946, 1982.PubMedGoogle Scholar
  94. 94.
    Gotoh K, Minamino R, Katoh O, et al. The role ot intracoronary thrombus in unstable angina: Angiographic assessment and thrombolytic therapy during ongoing angina attacks. Circulation 77:526, 1988.PubMedGoogle Scholar
  95. 95.
    Bar FW, Verheugt FW, Col J, et al. Thrombolysis in patients with unstable angina improves the angiographic but not the clinical outcome: Results ot UNASEM, a multicenter, randomized, placebo-controlled, clinical trial with amstreplase. Circulation 86:131, 1992.PubMedGoogle Scholar
  96. 96.
    The TIMI III Investigators. Early effects of tissue-type plasminogen activator added to conventional therapy on the culprit coronary lesion in patients presenting with ischemic cardiac pain at rest. Results of the Thrombolysis in Myocardial Ischemia (TIMI IIIA) Trial. Circulation 87:38, 1993.Google Scholar
  97. 97.
    The TIMI III Investigators. Effects ot tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q wave myocardial infarction. Results ot the TIMI IIIB Trial. Thromobolysis in Myocardial Ischemia. Circulation 89:1545, 1994.Google Scholar
  98. 98.
    Waters D, Lam JY. Is thrombolytic therapy striking out in unstable angina? Circulation 86:1642, 1992.PubMedGoogle Scholar
  99. 99.
    Ouimet TP, McCans J. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 319:1105, 1988.PubMedCrossRefGoogle Scholar
  100. 100.
    Lewis HD, Davis JW, Archibald DG. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina: Results of a Veterans Administration cooperative study. N Engl J Med 309:396, 1983.PubMedCrossRefGoogle Scholar
  101. 101.
    Cairns JA, Gent M, Senger J. Aspirin, sulfinpyrazone, or both in unstable angina: Results of a Canadian multicenter trial. N Engl J Med 1985:1369.Google Scholar
  102. 102.
    Telford AM, Wilson C. Trial of heparin versus atenelol in prevention ot myocardial infarction in intermediate coronary syndrome. Lancet 1:1225, 1981.PubMedGoogle Scholar
  103. 103.
    Willerson JT, Casscells W. Thrombin inhibitors in unstable angina: Rebound or continuation of angina after argatroban withdrawal? J Am Coll Cardiol 21:1048, 1993.PubMedGoogle Scholar
  104. 104.
    Weitz JI, Hudoba M, Massel D, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 86:385. 1990.PubMedGoogle Scholar
  105. 105.
    Hirsh J. Heparin. N Engl J Med 324:1565, 1991.PubMedCrossRefGoogle Scholar
  106. 106.
    Maraganore JM, Bourdon P, Adelman B, et al. Heparin variability and resistance: Comparisons with a direct thrombin inhibitor. Circulation 86(Suppl. D:1386, 1992.Google Scholar
  107. 107.
    Topol EJ, Fuster V, Harrington RA, et al. Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial. Circulation 89:1557, 1994.PubMedGoogle Scholar
  108. 108.
    Cannon CP, Braunwald E. Hirudin: Initial results in acute myocardial infarction, unstable angina and angioplasty. J Am Coll Cardiol 25(Suppl.):30S, 1995.Google Scholar
  109. 109.
    The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO IIA) Investigators. A randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 90:1631, 1994.Google Scholar
  110. 110.
    Fuchs J, Cannon CP, The TIMI 7 Investigators. Hirulog in the treatment of unstable angina: Results of the Thrombin Inhibition in Myocardial Ischemia (TIMI) 7 Trial. Circulation 92:727, 1995.PubMedGoogle Scholar
  111. 111.
    Neri Serneri GG, Gensini GF, Cinobali M, et al. Association between time ot increased hbrinopeptide A levels in plasma and episodes of spontaneous angina: A controlled prospective study. Am Heart J 113:672, 1987.PubMedGoogle Scholar
  112. 112.
    Theroux P, Latour JG, Leger-Gauthier C, Lara JD. Fibrinopeptide A and platelet factor levels in unstable angina pectoris. Circulation 75:156, 1987.PubMedGoogle Scholar
  113. 113.
    Yasu T, Oshima S, Imanishi M, et al. Effects of aspirin DL-lysine on thrombin generation in unstable angina pectoris. Am J Cardiol 71:1164, 1993.PubMedGoogle Scholar
  114. 114.
    Lam JYT, Latour JG, Lesperance J, Waters D. Platelet aggregation, coronary artery disease progression and future coronary artery events. Am J Cardiol 73:333, 1994.PubMedGoogle Scholar
  115. 115.
    Coller BS, Anderson KM, Weisman HF. Inhibitors of platelet aggregation: GP IIb/IIIa antagonists. In Braunwald E (ed). Heart Disease (Update). Philadelphia: WB, Saunders, 1995:4.Google Scholar
  116. 116.
    Simoons ML, Jan de Boer M, van den Brand MJBM. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. Circulation 89:596, 1994.PubMedGoogle Scholar
  117. 117.
    The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein Iib/IIIa receptor in high risk coronary angioplasty. N Engl J Med 330:956, 1994.Google Scholar
  118. 118.
    Topol EJ, Califf RM, Weisman HF, et al. for the EPIC Investigators. Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of restenosis results at six months. Lancet 343:881, 1994.PubMedGoogle Scholar
  119. 119.
    Tcheng JE, Ellis SG, Kleiman NS, et al. Outcome of patients treated with GPIIb/IIIa inhibitor integrelin during coronary angioplasty: Results of the IMPACT study. Circulation 88(Suppl. II):II595, 1993.Google Scholar
  120. 120.
    Gibson RS. Clinical, functional and angiographic distinctions between Q wave and non-Q wave myocardial infarction: Evidence of spontaneous reperfusion and implications for intervention trials. Circulation 75(Suppl. V):V128, 1987.PubMedGoogle Scholar
  121. 121.
    Braunwald E. Acute myocardial infarction — The value of being prepared. N Engl J Med 34:51, 1996.Google Scholar
  122. 122.
    Huey BL, Gheorghiade M, Crampton RS, et al. Acute non-Q wave myocardial infarction associated with early ST segment elevation: Evidence for spontaneous coronary reperfusion and implications for thrombolytic trials. J Am Coll Cardiol 9:18, 1987.PubMedGoogle Scholar
  123. 123.
    Ambrose JA, Hjemdahl-Monsen CE, Borrico S, et al. Angiographic demonstration of a common link between unstable angina pectoris and non-Q wave acute myocardial infarction. Am J Cardiol 61:244, 1988.PubMedGoogle Scholar
  124. 124.
    DeWood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q wave myocardial infarction. N Engl J Med 315:417, 1986.PubMedCrossRefGoogle Scholar
  125. 125.
    Rivera W, Sharaf BL, Miele NJ, et al. Coronary anatomy in patients who present with non-Q wave myocardial infarction differs from unstable angina pectoris: A report from TIMI 3B. Circulation 90: 1–438, 1994.Google Scholar
  126. 126.
    Davies MJ. Thrombosis and coronary atherosclerosis. In Julian D, Kubier W, Norris RM, Swan HJC, Collen D, Verstraete M (eds). Thrombolysis in Cardiovascular Disease. New York: Marcel Dekker, 1989:25.Google Scholar
  127. 127.
    GISSI (Gruppo Italiano per lo Studio della Strptochinasi nell’ Infarcto Miocardico): Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1:397, 1986.Google Scholar
  128. 128.
    ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial on intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 2:349, 1988.Google Scholar
  129. 129.
    Wilhelmsen L, Svarsudd K, Korsan-Bengsten K, et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 311:501, 1984.PubMedCrossRefGoogle Scholar
  130. 130.
    Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischemic heart disease: Principal results of the Northwick Park Heart Study. Lancet 2:533, 1986.PubMedGoogle Scholar
  131. 131.
    Hawkins R. Smoking, platelets and thrombosis. Nature 236:450, 1972.PubMedGoogle Scholar
  132. 132.
    Ridker PM, Manson JE, Buring JE, et al. Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. Circulation 82:897, 1990.PubMedGoogle Scholar
  133. 133.
    Brexinski DA, Tofier GA, Muller JE, et al. Morning increase in platelet aggregability: Association with the assumption of the upright posture. Circulation 78:35, 1988.Google Scholar
  134. 134.
    Santamore WP, Yelton BW, Ogilby JD. Dynamics of coronary occlusion in the pathogenesis of myocardial infarction. J Am Coll Cardiol 18:1397, 1991.PubMedGoogle Scholar
  135. 135.
    DeWood MA, Spores J, Notske RN, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 303:897, 1980.PubMedCrossRefGoogle Scholar
  136. 136.
    Verstraete M, Bory M, Collen D, et al. Randomized trial of intravenous recombinant tissue-type plasminogen activator versus intavenous streptokinase in acute myocardial infarction. Lancet 1:842, 1985.PubMedGoogle Scholar
  137. 137.
    The TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. N Engl J Med 312:932, 1985.Google Scholar
  138. 138.
    Neuhaus KL for the GAUS Study Group. Intarvenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: Results of the German Activator Urokinase Study (GAUS). J Am Coll Cardiol 12:581, 1988.Google Scholar
  139. 139.
    Bonnier HJRM, Visser RF, Klomps HC, Hoffmann HJML, Dutch Invasive Reperfusion Study Group. Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction. Am J Cardiol 62:25, 1988.PubMedGoogle Scholar
  140. 140.
    Rentrop P, Blanke H, Karsch KR, et al. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 63:307, 1981.PubMedGoogle Scholar
  141. 141.
    Topol EJ. Thrombolysis. In Topol EJ (ed). Textbook of Interventional Cardiology. Philadelphia: WB Saunders, 1990:77.Google Scholar
  142. 142.
    The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 329:1615, 1993.Google Scholar
  143. 143.
    Ambrose JA, Winters SL, Arora RR, et al. Coronary angiographic morphology in myocardial infarction: A link between the pathogenesis of unstable angina and myocardial infarction. J Am Coll Cardiol 6:1233, 1985.PubMedGoogle Scholar
  144. 144.
    Wilson RF, Holida MD, White CW. Quantitative angiographie morphology of coronary stenosis leading to myocardial infarction or unstable angina. Circulation 73:286, 1986.PubMedGoogle Scholar
  145. 145.
    Brown BG, Gallery CA, Badger RS, et al. Incomplete lysis of thrombus in the moderate underlying atherosclerotic lesion during intracoronary infusion of streptokinase for acute myocardial infarction: Quantitative angiographic observations. Circulation 73:653, 1986.PubMedGoogle Scholar
  146. 146.
    Davies SW, Marchant B, Lyons JP, et al. Coronary lesion morphology in acute myocardial infarction: Demonstration of early remodeling after streptokinase treatment. J Am Coll Cardiol 16:1079, 1990.PubMedGoogle Scholar
  147. 147.
    Veen G, Meijer A, Werter CJPJ, et al. Dynamic changes of culprit lesion morphology and severity after successful thrombolysis for acute myocardial infarction: An angiographic follow-up study. J Am Coll Cardiol 23:147A, 1994.Google Scholar
  148. 148.
    Davies SW, Marchant B, Lyons JP, et al. Irregular coronary lesion morphology after thrombolysis predicts early clinical instability. J Am Coll Cardiol 18:669, 1991.PubMedGoogle Scholar
  149. 149.
    Forrester JS, Litvack F, Grundfest W, Hickey A. A perspective of coronary disease seen through the arteries of living man. Circulation 75:505, 1987.PubMedGoogle Scholar
  150. 150.
    The TIMI Study Group. Comparison of invasive and conservative strategies following intravenous tissue plasminogen activator in acute myocardial infarction: Results of the thrombolysis in myocardial infarction (TIMI) II trial. N Engl J Med 320:618, 1989.CrossRefGoogle Scholar
  151. 151.
    Topol EJ, Califf RM, George BS, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 317:581, 1987.PubMedCrossRefGoogle Scholar
  152. 152.
    Webster MWI, Cheseboro JH, Smith HC, et al. Myocardial infarction and coronary artery occlusion: A prospective 5-year angiographie study. J Am Coll Cardiol 15:218A, 1990.Google Scholar
  153. 153.
    Laffel GL, Braunwald E. Thrombolytic therapy. A new strategy for treatment of acute myocardial infarction. N Engl J Med 311:710, 1984.PubMedCrossRefGoogle Scholar
  154. 154.
    Gruppo Italiano Per Lo Studio Delia Sopravvivenza Nell Infarcto Miocardico: GISSI-2: A factorial randomized trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 336:65, 1990.Google Scholar
  155. 155.
    The GUSTO Investigators: An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329:673, 1993.Google Scholar
  156. 156.
    Cannon CP, McCabe CH, Henry TD, et al. A pilot trial of recombinant disulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 5 trial. J Am Coll Cardiol 23:993, 1994.PubMedGoogle Scholar
  157. 157.
    Neuhaus K-L, Niederer W, Wagner J, et al. HIT (Hirdin for the Improvement of Thrombolysis): Results of a dose escalation study (abstr). Circulation 88:1–292, 1993.Google Scholar
  158. 158.
    Lee LV, for the TIMI 6 Investigators. Initial experience with hirudin and streptokinase in acute myocardial infarction: Results of the TIMI 6 trial. Am J Cardiol 75:7, 1995.PubMedGoogle Scholar
  159. 159.
    Antman EM, for the TIMI 9A Investigators. Hirudin in acute myocardial infarction: Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A trial. Crculation 90:1624, 1994.Google Scholar
  160. 160.
    The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators. A randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 90:1631, 1994.Google Scholar
  161. 161.
    Neuhaus K-L, von Essen R, Tebbe U, et al. Safety observations from the pilot phase of a randomized trial: r-Hirudin for Improvement of Thrombolysis (HIT-III) Study. A study of the Arbeitsgemein-schaft Leitender, Kardiologischer Koinkenhausarzte (ALKK). Circulation 90:1638, 1994.PubMedGoogle Scholar
  162. 162.
    Langer A, Freeman MR, Armstrong PW. ST segment shift in unstable angina: Pathophysiology and association with coronary anatomy and hospital outcome. J Am Coll Cardiol 13:1495, 1989.PubMedCrossRefGoogle Scholar
  163. 163.
    Davies MJ, Thomas A. Thrombosis and acute coronary lesions in sudden cardiac ischemic death. N Engl J Med 310:1137, 1984.PubMedCrossRefGoogle Scholar
  164. 164.
    Warnes CA, Roberts WC. Sudden coronary death: Relation of amount and distribution of coronary narrowing at necropsy to previous symptoms of myocardial ischemia, left ventricular scarring and heart weight. Am J Cardiol 54:65, 1984.PubMedGoogle Scholar
  165. 165.
    Baroldi G, Falzi G, Mariani F. Sudden coronary death: A postmortem study in 208 selected cases compared to 97 “control” subjects. Am Heart J 98:20, 1979.PubMedGoogle Scholar
  166. 166.
    Davies MJ, Bland JM, Hangartner JRW, et al. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J 10:203, 1989.PubMedGoogle Scholar
  167. 167.
    Roberts WC. Qualitative and quantitative comparison of amounts of narrowing by atherosclerotic plaques in the major epicardial coronary arteries at necropsy in sudden death, transmural acute myocardial infarction, transmural healed myocardial infarction and unstable angina pectoris. Am J Cardiol 64:324, 1989.PubMedGoogle Scholar

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© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Narinder P. Bhalla
  • John A. Ambrose

There are no affiliations available

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