The role of the vulnerable plaque in acute coronary syndromes
- Fumiyuki Otsuka, MD, PhD
Fumiyuki Otsuka, MD, PhD
- Bioresource Section, NCVC Biobank
- Department of Cardiovascular Medicine
- National Cerebral and Cardiovascular Center
- Frank Kolodgie, PhD
Frank Kolodgie, PhD
- Associate Director
- CVPath Institute, Inc.
- Renu Virmani, MD
Renu Virmani, MD
- President & Medical Director
- CVPath Institute, Inc.
- Clinical Professor of Pathology
- Georgetown University
- Clinical Professor of Pathology
- George Washington University
- Section Editors
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
- Peter Libby, MD
Peter Libby, MD
- Section Editor — Coronary Heart Disease
- Chief, Cardiovascular Medicine
- Brigham and Women's Hospital
- Professor, Harvard Medical School
Acute coronary syndromes (ACS) represent a spectrum in the clinical manifestations of acute coronary artery disease that includes unstable angina, acute myocardial infarction, and sudden coronary arrest. (See "Classification of unstable angina and non-ST elevation myocardial infarction" and "Criteria for the diagnosis of acute myocardial infarction" and "Pathophysiology and etiology of sudden cardiac arrest" and "Pathophysiology and etiology of sudden cardiac arrest", section on 'Myocardial ischemia and infarction'.)
Coronary artery thrombosis is the final pathogenic mechanism of most cases with ACS, as documented by angiographic and pathologic studies [1,2]. For example, coronary artery thrombi are found in 50 to 75 percent of cases of sudden cardiac death. (See "The role of platelets in coronary heart disease".)
The formation of an intraluminal clot is thought to result from the loss of integrity of a protective covering over an atherosclerotic plaque. In healthy arteries, a single layer of endothelial cells separates the blood from potentially thrombogenic components of the arterial medial layer, both of which are referred to as vulnerable plaques. The loss of integrity of the protective covering occurs with processes called plaque rupture or erosion. This disruption allows blood to come in contact with the highly thrombogenic contents of the necrotic core of the plaque and luminal thrombosis to occur [3,4]. Intraluminal thrombosis after exposure of blood to calcified nodules has also been observed. Other mechanisms of ACS, such as a supply-demand mismatch, have been postulated.
Plaque rupture or erosion often occurs at sites where luminal stenosis is angiographically modest [5,6]. Autopsy studies of sudden coronary death victims have shown that approximately 40 percent of plaque ruptures occur at lesion sites with less than 50 percent diameter stenosis . In instances when rupture or erosion does not lead to thrombotic occlusion of the vessel, each event may not necessarily cause symptoms and plaque healing with progression may occur [8,9].
This topic focuses on the contribution of plaque rupture to the development of ACS as well as potential strategies to detect and treat vulnerable plaques. The underlying pathology and pathogenesis of coronary plaque progression, including rupture, are reviewed separately. (See "Pathology and pathogenesis of the vulnerable plaque".)
Subscribers log in hereLiterature review current through: Dec 2016. | This topic last updated: Mon May 11 00:00:00 GMT 2015.References
- DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303:897.
- Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985; 71:699.
- Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20:1262.
- Burke AP, Farb A, Malcom GT, et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 1999; 281:921.
- Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988; 12:56.
- Glaser R, Selzer F, Faxon DP, et al. Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention. Circulation 2005; 111:143.
- Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93:1354.
- Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001; 103:934.
- Mann J, Davies MJ. Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart 1999; 82:265.
- Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310:1137.
- el Fawal MA, Berg GA, Wheatley DJ, Harland WA. Sudden coronary death in Glasgow: nature and frequency of acute coronary lesions. Br Heart J 1987; 57:329.
- Davies MJ, Bland JM, Hangartner JR, et al. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J 1989; 10:203.
- Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336:1276.
- Burke AP, Farb A, Malcom GT, et al. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation 1998; 97:2110.
- Arbustini E, Dal Bello B, Morbini P, et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 1999; 82:269.
- Nemerson Y. A simple experiment and a weakening paradigm: the contribution of blood to propensity for thrombus formation. Arterioscler Thromb Vasc Biol 2002; 22:1369.
- Kramer MC, Rittersma SZ, de Winter RJ, et al. Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J Am Coll Cardiol 2010; 55:122.
- Ferrante G, Nakano M, Prati F, et al. High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinicopathological study. Circulation 2010; 122:2505.
- Kolodgie FD, Burke AP, Farb A, et al. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion. Arterioscler Thromb Vasc Biol 2002; 22:1642.
- Xu Y, Mintz GS, Tam A, et al. Prevalence, distribution, predictors, and outcomes of patients with calcified nodules in native coronary arteries: a 3-vessel intravascular ultrasound analysis from Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT). Circulation 2012; 126:537.
- Kubo T, Imanishi T, Takarada S, et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol 2007; 50:933.
- Ino Y, Kubo T, Tanaka A, et al. Difference of culprit lesion morphologies between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study. JACC Cardiovasc Interv 2011; 4:76.
- Hong YJ, Jeong MH, Choi YH, et al. Differences in intravascular ultrasound findings in culprit lesions in infarct-related arteries between ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction. J Cardiol 2010; 56:15.
- Roberts WC, Kragel AH, Gertz SD, Roberts CS. Coronary arteries in unstable angina pectoris, acute myocardial infarction, and sudden coronary death. Am Heart J 1994; 127:1588.
- Kragel AH, Gertz SD, 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 1991; 18:801.
- Roberts WC. Qualitative and quantitative comparison of amounts of narrowing by atherosclerotic plaques in the major epicardial coronary arteries at necropsy in sudden coronary death, transmural acute myocardial infarction, transmural healed myocardial infarction and unstable angina pectoris. Am J Cardiol 1989; 64:324.
- Roberts WC, Virmani R. Quantification of coronary arterial narrowing in clinically-isolated unstable angina pectoris. An analysis of 22 necropsy patients. Am J Med 1979; 67:792.
- Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47:C13.
- Kolodgie FD, Burke AP, Farb A, et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 2001; 16:285.
- Levin DC, Fallon JT. Significance of the angiographic morphology of localized coronary stenoses: histopathologic correlations. Circulation 1982; 66:316.
- Ambrose JA, Winters SL, Stern A, et al. Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985; 5:609.
- Ambrose JA, Winters SL, Arora RR, et al. Angiographic evolution of coronary artery morphology in unstable angina. J Am Coll Cardiol 1986; 7:472.
- Kaski JC, Chester MR, Chen L, Katritsis D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology. Circulation 1995; 92:2058.
- Chen L, Chester MR, Redwood S, et al. Angiographic stenosis progression and coronary events in patients with 'stabilized' unstable angina. Circulation 1995; 91:2319.
- Chester MR, Chen L, Kaski JC. The natural history of unheralded complex coronary plaques. J Am Coll Cardiol 1996; 28:604.
- Goldstein JA, Demetriou D, Grines CL, et al. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 2000; 343:915.
- Asakura M, Ueda Y, Yamaguchi O, et al. Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. J Am Coll Cardiol 2001; 37:1284.
- Hong MK, Mintz GS, Lee CW, et al. Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: a three-vessel intravascular ultrasound study in 235 patients. Circulation 2004; 110:928.
- Burke A, Virmani R. Significance of multiple coronary artery thrombi. A consequence of diffuse atherosclerotic disease? Ital Heart J 2000; 1:832.
- Sano T, Tanaka A, Namba M, et al. C-reactive protein and lesion morphology in patients with acute myocardial infarction. Circulation 2003; 108:282.
- Tanaka A, Shimada K, Sano T, et al. Multiple plaque rupture and C-reactive protein in acute myocardial infarction. J Am Coll Cardiol 2005; 45:1594.
- Kusama I, Hibi K, Kosuge M, et al. Impact of plaque rupture on infarct size in ST-segment elevation anterior acute myocardial infarction. J Am Coll Cardiol 2007; 50:1230.
- Tanaka A, Imanishi T, Kitabata H, et al. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: an optical coherence tomography study. Circulation 2008; 118:2368.
- Toutouzas K, Tsiamis E, Karanasos A, et al. Morphological characteristics of culprit atheromatic plaque are associated with coronary flow after thrombolytic therapy: new implications of optical coherence tomography from a multicenter study. JACC Cardiovasc Interv 2010; 3:507.
- Burke AP, Kolodgie FD, Farb A, et al. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002; 105:297.
- Varnava AM, Mills PG, Davies MJ. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 2002; 105:939.
- Achenbach S, Ulzheimer S, Baum U, et al. Noninvasive coronary angiography by retrospectively ECG-gated multislice spiral CT. Circulation 2000; 102:2823.
- Hoffmann MH, Shi H, Schmitz BL, et al. Noninvasive coronary angiography with multislice computed tomography. JAMA 2005; 293:2471.
- Schroeder S, Kopp AF, Baumbach A, et al. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am Coll Cardiol 2001; 37:1430.
- Leber AW, Knez A, Becker A, et al. Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 2004; 43:1241.
- Hoffmann U, Moselewski F, Nieman K, et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol 2006; 47:1655.
- Motoyama S, Sarai M, Harigaya H, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 2009; 54:49.
- Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011; 364:226.
- Kubo T, Maehara A, Mintz GS, et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol 2010; 55:1590.
- Burke AP, Tracy RP, Kolodgie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 2002; 105:2019.
- Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2006; 26:2523.
- Lp-PLA(2) Studies Collaboration, Thompson A, Gao P, et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 2010; 375:1536.
- Epps KC, Wilensky RL. Lp-PLA₂- a novel risk factor for high-risk coronary and carotid artery disease. J Intern Med 2011; 269:94.
- Mallat Z, Lambeau G, Tedgui A. Lipoprotein-associated and secreted phospholipases A₂ in cardiovascular disease: roles as biological effectors and biomarkers. Circulation 2010; 122:2183.
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383.
- Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333:1301.
- Fukumoto Y, Libby P, Rabkin E, et al. Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation 2001; 103:993.
- Bustos C, Hernández-Presa MA, Ortego M, et al. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol 1998; 32:2057.
- Johnson J, Carson K, Williams H, et al. Plaque rupture after short periods of fat feeding in the apolipoprotein E-knockout mouse: model characterization and effects of pravastatin treatment. Circulation 2005; 111:1422.
- Takano M, Mizuno K, Yokoyama S, et al. Changes in coronary plaque color and morphology by lipid-lowering therapy with atorvastatin: serial evaluation by coronary angioscopy. J Am Coll Cardiol 2003; 42:680.
- Schartl M, Bocksch W, Koschyk DH, et al. Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation 2001; 104:387.
- Kawasaki M, Sano K, Okubo M, et al. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol 2005; 45:1946.
- Otsuka F, Hibi K, Kusama I, et al. Impact of statin pretreatment on the incidence of plaque rupture in ST-elevation acute myocardial infarction. Atherosclerosis 2010; 213:505.
- Takarada S, Imanishi T, Kubo T, et al. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: assessment by optical coherence tomography study. Atherosclerosis 2009; 202:491.
- PLAQUE FEATURES RESPONSIBLE FOR ACUTE THROMBOSIS
- Plaque rupture
- Plaque erosion
- Calcified nodule
- PLAQUE MORPHOLOGY IN ACUTE CORONARY SYNDROMES
- Sudden cardiac death
- Acute myocardial infarction
- Unstable angina
- Age and sex differences
- Other correlates
- Repeat plaque ruptures
- OBSERVATIONS IN PATIENTS WITH PLAQUE RUPTURE
- VULNERABLE PLAQUES AND FUTURE RUPTURE
- Identification of vulnerable plaque by CT
- Natural history
- RISK FACTORS AND FATAL PLAQUES
- STATIN THERAPY