Pathophysiology and clinical significance of atherosclerotic plaque rupture.

Atherosclerotic plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes. These syndromes include unstable angina, non-Q-wave myocardial infarction (MI) and Q-wave MI. In addition, many cases of sudden cardiac death may be attributable to atherosclerotic plaque disruption and its immediate complications. Our understanding of the atherosclerotic process and the pathophysiology of plaque disruption has advanced remarkably. Despite these advances, event rates after acute coronary syndromes remain unacceptably high. This review will focus on the pathophysiology underlying atherosclerotic plaque development, the sequellae of coronary plaque rupture, and current therapies designed to treat the acute coronary syndromes. It is hoped that as our understanding of the atherosclerotic plaque improves, treatment strategies for the acute coronary syndromes will advance.

[1]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[2]  A. Maseri,et al.  Vasoreactivity of the Culprit Lesion in Unstable Angina , 1994, Circulation.

[3]  T. Pedersen,et al.  Review of cholesterol-lowering therapy: coronary angiographic and events trials. , 1996, The American journal of medicine.

[4]  J. Mcmanus.  Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction: Results of the TIMI IIIB trial: The TIMI IIIB Investigators Circulation 89:1545–1556 Apr 1994 , 1994 .

[5]  K. Wiklund,et al.  Low-molecular-weight heparin during instability in coronary artery disease , 1996 .

[6]  M J Davies,et al.  Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. , 1984, The New England journal of medicine.

[7]  J. Herrick.  CLINICAL FEATURES OF SUDDEN OBSTRUCTION OF THE CORONARY ARTERIES , 1912 .

[8]  J. Eidt,et al.  Specific Platelet Mediators and Unstable Coronary Artery Lesions: Experimental Evidence and Potential Clinical Implications , 1989, Circulation.

[9]  A. Gotto.  Cholesterol management in theory and practice. , 1997, Circulation.

[10]  M. Davies.  The composition of coronary-artery plaques. , 1997, The New England journal of medicine.

[11]  D. Steinberg,et al.  Role of oxidized low density lipoprotein in atherogenesis. , 1991, The Journal of clinical investigation.

[12]  V. Fuster,et al.  Regression or stabilization of atherosclerosis means regression or stabilization of what we don't see in the arteriogram. , 1995, European heart journal.

[13]  K. Woo,et al.  Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. , 1997, Circulation.

[14]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[15]  A. Yeung,et al.  The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. , 1995, The New England journal of medicine.

[16]  G. V. R. Born,et al.  INFLUENCE OF PLAQUE CONFIGURATION AND STRESS DISTRIBUTION ON FISSURING OF CORONARY ATHEROSCLEROTIC PLAQUES , 1989, The Lancet.

[17]  L. Shaw,et al.  Early and 1-year clinical outcome of patients' evolving non-Q-wave versus Q-wave myocardial infarction after thrombolysis. Results from The TIMI II Study. , 1995, Circulation.

[18]  P. Collinson,et al.  A prospective study of the role of lipoprotein(a) in the pathogenesis of unstable angina. , 1997, European heart journal.

[19]  R. Califf,et al.  A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. , 1997 .

[20]  Thrombolysis for acute myocardial infarction. , 1998, Circulation.

[21]  M J Davies,et al.  Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. , 1996, Circulation.

[22]  R. D'Agostino,et al.  Sudden coronary death in women. , 1998, American heart journal.

[23]  A. Moss,et al.  Risk of subsequent cardiac events in stable convalescing patients after first non‐Q-wave and Q‐wave myocardial infarction: the limited role of non‐invasive testing , 1994, Coronary artery disease.

[24]  E. Tremoli,et al.  Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[25]  M. Pfeffer,et al.  Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats. , 1995, Circulation.

[26]  R. Califf,et al.  Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators. , 1997, Circulation.

[27]  E. Gurfinkel,et al.  Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study , 1997, The Lancet.

[28]  Z. Ba,et al.  Administration of tumor necrosis factor-alpha in vivo depresses endothelium-dependent relaxation. , 1994, The American journal of physiology.

[29]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[30]  M. Davies,et al.  Anatomic features in victims of sudden coronary death. Coronary artery pathology. , 1992, Circulation.

[31]  P. Libby,et al.  Apoptosis of Vascular Smooth Muscle Cells Induced by In Vitro Stimulation With Interferon-γ, Tumor Necrosis Factor–α, and Interleukin-1β , 1996 .

[32]  M. Woodward,et al.  Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study. , 1998, European heart journal.

[33]  M. Janse,et al.  Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. , 1989, Physiological reviews.

[34]  W. Nieuwenhuizen.  Biochemistry and measurement of fibrinogen. , 1995, Ukrainskii biokhimicheskii zhurnal.

[35]  C D Naylor,et al.  Population-wide mortality trends among patients hospitalized for acute myocardial infarction: the Ontario experience, 1981 to 1991. , 1994, Journal of the American College of Cardiology.

[36]  W. Jacob,et al.  Apoptosis and related proteins in different stages of human atherosclerotic plaques. , 1998, Circulation.

[37]  B. Björkerud,et al.  Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. , 1996, The American journal of pathology.

[38]  J. Sixma,et al.  Plasminogen activator inhibitor-1 released from activated platelets plays a key role in thrombolysis resistance. Studies with thrombi generated in the Chandler loop. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[39]  Walker,et al.  Collaborative overview of randomised trials of antiplatelet therapy Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients , 1994 .

[40]  G. Thorgeirsson,et al.  Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study. , 1996, Circulation.

[41]  P. Libby,et al.  Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. , 1998, Circulation.

[42]  M. Leon,et al.  Determinants and correlates of target lesion calcium in coronary artery disease: a clinical, angiographic and intravascular ultrasound study. , 1997, Journal of the American College of Cardiology.

[43]  A. Becker,et al.  Sudden cardiac death and acute pathology of coronary arteries. , 1986, European heart journal.

[44]  M. Creager,et al.  Impaired Endothelium‐Dependent Vasodilation in Patients With Insulin‐Dependent Diabetes Mellitus , 1993, Circulation.

[45]  K. Mizuno,et al.  Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. , 1992, The New England journal of medicine.

[46]  P. Macfarlane,et al.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia , 1995 .

[47]  A. Gasbarrini,et al.  Association of virulent Helicobacter pylori strains with ischemic heart disease. , 1998, Circulation.

[48]  V. Fuster,et al.  The Unstable Atherosclerotic Plaque: Clinical Significance and Therapeutic Intervention , 1997, Thrombosis and Haemostasis.

[49]  David W. Banner,et al.  The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor , 1996, Nature.

[50]  M. Debakey,et al.  Possible role of cytomegalovirus in atherogenesis. , 1990, JAMA.

[51]  Epic Investigators,et al.  Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. , 1994, The New England journal of medicine.

[52]  D. Harrison,et al.  Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. , 1996, The Journal of clinical investigation.

[53]  R. Shebuski,et al.  Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis. , 1990, Circulation.

[54]  P. Vallance,et al.  Endothelial "stunning" following a brief exposure to endotoxin: a mechanism to link infection and infarction? , 1996, Cardiovascular research.

[55]  B. Rollins,et al.  Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells* , 1997, The Journal of Biological Chemistry.

[56]  V. Fuster,et al.  Angiographic progression of coronary artery disease and the development of myocardial infarction. , 1988, Journal of the American College of Cardiology.

[57]  V. Fuster,et al.  Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. , 1994, Circulation.

[58]  V. Fuster,et al.  Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. , 1998, Circulation.

[59]  P. Libby,et al.  Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Y. Uchida,et al.  Fiberoptic observation of thrombosis and thrombolysis in isolated human coronary arteries. , 1986, American heart journal.

[61]  V. Fuster,et al.  Pathophysiologic bases for adjunctive therapies in the treatment and secondary prevention of acute myocardial infarction , 1998, Clinical cardiology.

[62]  Daniel B. Mark,et al.  Diagnosing and managing unstable angina. Agency for Health Care Policy and Research. , 1994, Circulation.

[63]  R. Gillum,et al.  Trends in acute myocardial infarction and coronary heart disease death in the United States. , 1994, Journal of the American College of Cardiology.

[64]  S. Manuck,et al.  Plaque changes and arterial enlargement in atherosclerotic monkeys after manipulation of diet and social environment. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[65]  W. Weintraub,et al.  Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. , 1995, The New England journal of medicine.

[66]  H. Gold,et al.  Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation. , 1988, Circulation.

[67]  D. Hosmer,et al.  A Communitywide Perspective of Sex Differences and Temporal Trends in the Incidence and Survival Rates After Acute Myocardial Infarction and Out‐of‐Hospital Deaths Caused by Coronary Heart Disease , 1993, Circulation.

[68]  D. Clement.  A randomised, blinded, trial of Clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) , 1996 .

[69]  K. Thygesen,et al.  Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial ischemia. , 1997, Circulation.

[70]  A. Becker,et al.  Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. , 1994, Circulation.

[71]  R. Virmani,et al.  Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. , 1997, The New England journal of medicine.

[72]  V. Fuster,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. , 1995, Circulation.

[73]  Gebhardt,et al.  International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina , 1998 .

[74]  K. Swedberg,et al.  Declining hospital mortality in acute myocardial infarction. , 1994, European heart journal.

[75]  V. Fuster,et al.  Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. , 1997, Circulation.

[76]  R. Virmani,et al.  Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. , 1998, Circulation.

[77]  C. di Ilio,et al.  Glutathione-related antioxidant defenses in human atherosclerotic plaques. , 1998, Circulation.

[78]  V. Fuster,et al.  Macrophage Infiltration in Acute Coronary Syndromes: Implications for Plaque Rupture , 1994, Circulation.

[79]  G. D. De Meyer,et al.  Cell composition, replication, and apoptosis in atherosclerotic plaques after 6 months of cholesterol withdrawal. , 1998, Circulation research.

[80]  M. Gheorghiade,et al.  Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies. , 1996, American heart journal.

[81]  M. Davies,et al.  Vulnerable plaque. Relation of characteristics to degree of stenosis in human coronary arteries. , 1996, Circulation.

[82]  Stgrp Capture,et al.  Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study , 1997, The Lancet.

[83]  E. Topol,et al.  Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. , 1994, Circulation.

[84]  M. Raffeld,et al.  Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. , 1992, The Journal of clinical investigation.

[85]  E. Braunwald,et al.  Unstable angina. A classification. , 1989, Circulation.

[86]  J. Demirovic,et al.  Epidemiology of sudden coronary death: an overview. , 1994, Progress in cardiovascular diseases.

[87]  R D Kamm,et al.  Mechanical properties of model atherosclerotic lesion lipid pools. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[88]  V. Fuster,et al.  27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 1. Pathogenesis of coronary disease: the biologic role of risk factors. , 1996, Journal of the American College of Cardiology.

[89]  V. Fuster,et al.  Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. , 1994, Journal of the American College of Cardiology.

[90]  Samin K. Sharma,et al.  Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes. , 1996, Circulation.

[91]  Benjamin Sovacool,et al.  Heart Disease, Cancer, and Stroke Mortalit Trends And Their Interrelations: An International Perspective , 1994, Circulation.

[92]  D. Stewart,et al.  Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. , 1995, The Journal of infectious diseases.

[93]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico.,et al.  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.

[94]  P. Libby.  Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[95]  B. Coller.  Inhibitors of the platelet glycoprotein IIb/IIIa receptor as conjunctive therapy for coronary artery thromboiysis , 1992 .

[96]  J MEAD,et al.  Mechanical properties of lungs. , 1961, Physiological reviews.

[97]  J. Ambrose,et al.  Thrombosis in ischemic heart disease. , 1996, Archives of internal medicine.

[98]  J. Beranek,et al.  FISSURES IN CORONARY ATHEROSCLEROTIC PLAQUES , 1989, The Lancet.

[99]  R. Bonow,et al.  Chronic heart failure in the United States: a manifestation of coronary artery disease. , 1998, Circulation.

[100]  W. Roberts,et al.  Sudden coronary death: comparison of patients with to those without coronary thrombus at necropsy. , 1984, The American journal of cardiology.

[101]  A. Camm,et al.  Elevated Chlamydia pneumoniae Antibodies, Cardiovascular Events, and Azithromycin in Male Survivors of Myocardial Infarction , 1997 .

[102]  M. Bond,et al.  Physicochemical and histological changes in the arterial wall of nonhuman primates during progression and regression of atherosclerosis. , 1984, The Journal of clinical investigation.

[103]  M. Leon,et al.  Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. , 1995, The American journal of pathology.

[104]  W D Wagner,et al.  A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[105]  C. Heeschen,et al.  Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. , 1997, The New England journal of medicine.

[106]  J. Cooper,et al.  Activation of the Coagulant Pathway in Cigarette Smokers , 1998, Thrombosis and Haemostasis.

[107]  R. Collins,et al.  Randomized, Double-blind Comparison of Hirulog Versus Heparin in Patients Receiving Streptokinase and Aspirin for Acute Myocardial Infarction (HERO) , 1997 .