Vulnerable plaque: definition, diagnosis, and treatment.

This article provides a systematic approach to vulnerable plaques. It is divided into 4 sections. The first section is devoted to definition, incidence, anatomic distribution, and clinical presentation. The second section is devoted to plaque composition, setting up the foundations to understand plaque vulnerability. The third section relates to invasive plaque imaging. The fourth section is devoted to therapy, from conservative pharmacologic options to aggressive percutaneous coronary intervention alternatives.

[1]  J. Ambrose,et al.  Preventing future acute coronary events: is the target the so-called vulnerable plaque or the high-risk or vulnerable patient? , 2009, Current opinion in cardiology.

[2]  Brett E. Bouma,et al.  In Vivo Characterization of Coronary Atherosclerotic Plaque by Use of Optical Coherence Tomography , 2005, Circulation.

[3]  T C Bakker Schut,et al.  On-line detection of cholesterol and calcification by catheter based Raman spectroscopy in human atherosclerotic plaque ex vivo , 2003 .

[4]  G. Berry,et al.  Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries. , 2000, American heart journal.

[5]  K. Jablonski,et al.  Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. , 2002, Journal of the American College of Cardiology.

[6]  Paul Baas,et al.  Photodynamic therapy in oncology. , 2006, The oncologist.

[7]  R. Virmani,et al.  Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. , 1996, Circulation.

[8]  S. Nakatani,et al.  Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. , 2000, Journal of the American College of Cardiology.

[9]  N. Obuchowski,et al.  Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data. , 2001, Ultrasound in Medicine and Biology.

[10]  Benjamin J Vakoc,et al.  Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging. , 2008, JACC. Cardiovascular imaging.

[11]  E. Falk.  Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. , 1983, British heart journal.

[12]  M Valgimigli,et al.  Coronary artery remodelling is related to plaque composition , 2005, Heart.

[13]  Renu Virmani,et al.  Intraplaque hemorrhage and progression of coronary atheroma. , 2003, The New England journal of medicine.

[14]  E. Tuzcu,et al.  Coronary Plaque Classification With Intravascular Ultrasound Radiofrequency Data Analysis , 2002, Circulation.

[15]  R. Virmani,et al.  IVUS-VH: a predictor of plaque morphology? , 2006, European heart journal.

[16]  Jean-Claude Tardif,et al.  In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study. , 2009, JACC. Cardiovascular imaging.

[17]  Hiroshi Fujita,et al.  Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis. , 2006, European heart journal.

[18]  N. Weissman,et al.  Attenuated plaque detected by intravascular ultrasound: clinical, angiographic, and morphologic features and post-percutaneous coronary intervention complications in patients with acute coronary syndromes. , 2009, JACC. Cardiovascular interventions.

[19]  Patrick W Serruys,et al.  Fourth annual American College of Cardiology international lecture: a journey in the interventional field. , 2006, Journal of the American College of Cardiology.

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

[21]  Ralph Weissleder,et al.  Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto‐optical nanoparticle , 2005, Magnetic resonance in medicine.

[22]  Christopher P Cannon,et al.  Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. , 2006, Journal of the American College of Cardiology.

[23]  James E. Muller,et al.  Detection of lipid core coronary plaques in autopsy specimens with a novel catheter-based near-infrared spectroscopy system. , 2008, JACC. Cardiovascular imaging.

[24]  Yasunori Ueda,et al.  Number of yellow plaques detected in a coronary artery is associated with future risk of acute coronary syndrome: detection of vulnerable patients by angioscopy. , 2006, Journal of the American College of Cardiology.

[25]  Stéphane G Carlier,et al.  Intravascular ultrasound profile analysis of ruptured coronary plaques. , 2006, The American journal of cardiology.

[26]  Ralph Weissleder,et al.  Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle , 2005, Circulation research.

[27]  Marc Sirol,et al.  Neovascularization in Human Atherosclerosis , 2006, Circulation.

[28]  Ron Waksman,et al.  Biodegradable stents: they do their job and disappear. , 2006, The Journal of invasive cardiology.

[29]  A. Becker,et al.  Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? , 1999, Cardiovascular research.

[30]  P. Libby,et al.  The smooth muscle cell: sinner or saint in restenosis and the acute coronary syndromes? , 1998, Journal of the American College of Cardiology.

[31]  P. Serruys,et al.  Global characterization of coronary plaque rupture phenotype using three-vessel intravascular ultrasound radiofrequency data analysis. , 2006, European heart journal.

[32]  James E. Muller,et al.  Detection and Treatment of Vulnerable Plaques and Vulnerable Patients: Novel Approaches to Prevention of Coronary Events , 2006, Circulation.

[33]  Y. Uchida,et al.  Prediction of acute coronary syndromes by percutaneous coronary angioscopy in patients with stable angina. , 1995, American heart journal.

[34]  A. Low,et al.  Technology Insight: optical coherence tomography—current status and future development , 2006, Nature Clinical Practice Cardiovascular Medicine.

[35]  L. Tavazzi,et al.  Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation , 2002, Heart.

[36]  S. Feinstein,et al.  Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. , 2006, Journal of the American College of Cardiology.

[37]  Renu Virmani,et al.  Pathophysiology of Calcium Deposition in Coronary Arteries , 2001, Herz.

[38]  A. Levy,et al.  Genetically Determined Heterogeneity in Hemoglobin Scavenging and Susceptibility to Diabetic Cardiovascular Disease , 2003, Circulation research.

[39]  V. Fuster,et al.  New aspects in the pathogenesis of diabetic atherothrombosis. , 2004, Journal of the American College of Cardiology.

[40]  Guy Ennekens,et al.  Validation of in vivo plaque characterisation by virtual histology in a rabbit model of atherosclerosis. , 2009, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[41]  M. Reilly,et al.  Pharmacological Activation of Liver X Receptors Promotes Reverse Cholesterol Transport In Vivo , 2005, Circulation.

[42]  P. Moreno,et al.  Detection of high-risk atherosclerotic coronary plaques by intravascular spectroscopy. , 2003, Journal of interventional cardiology.

[43]  W. Markiewicz,et al.  Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. , 2005, Diabetes.

[44]  J. Willerson,et al.  Intracoronary thermography for detection of high-risk vulnerable plaques. , 2006, Journal of the American College of Cardiology.

[45]  Bin Liu,et al.  Assessment of coronary plaque collagen with polarization sensitive optical coherence tomography (PS-OCT). , 2006, International journal of cardiology.

[46]  Chun Yuan,et al.  Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study , 2005, Circulation.

[47]  E. Halpern,et al.  Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography , 2003, Circulation.

[48]  V. Fuster,et al.  Fenofibrate induces plaque regression in hypercholesterolemic atherosclerotic rabbits: in vivo demonstration by high-resolution MRI. , 2007, Atherosclerosis.

[49]  Antonio Colombo,et al.  Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. , 2004, European heart journal.

[50]  E. Falk,et al.  Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and interventional research. , 2009, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[51]  A. Levy.  Haptoglobin: a major susceptibility gene for diabetic cardiovascular disease. , 2004, The Israel Medical Association journal : IMAJ.

[52]  M. Davies.  Detecting vulnerable coronary plaques , 1996, The Lancet.

[53]  P. Barter,et al.  High-Density Lipoproteins Enhance Progenitor-Mediated Endothelium Repair in Mice , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[54]  Chun Yuan,et al.  Association Between Carotid Plaque Characteristics and Subsequent Ischemic Cerebrovascular Events: A Prospective Assessment With MRI—Initial Results , 2006, Stroke.

[55]  Juan J. Badimon,et al.  Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta: Implications for Plaque Vulnerability , 2004, Circulation.

[56]  Zahi A Fayad,et al.  Atherothrombosis and high-risk plaque: Part II: approaches by noninvasive computed tomographic/magnetic resonance imaging. , 2005, Journal of the American College of Cardiology.

[57]  M. Sabatine,et al.  Intensive statin therapy and the risk of hospitalization for heart failure after an acute coronary syndrome in the PROVE IT-TIMI 22 study. , 2006, Journal of the American College of Cardiology.

[58]  J. Muller,et al.  Near-infrared spectroscopy for the detection of vulnerable coronary artery plaques. , 2006, Journal of the American College of Cardiology.

[59]  T. Lüscher,et al.  Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin , 2004, Circulation research.

[60]  E. Tuzcu,et al.  Attenuated plaque at nonculprit lesions in patients enrolled in intravascular ultrasound atherosclerosis progression trials. , 2009, JACC. Cardiovascular interventions.

[61]  V. Fuster,et al.  Neovascularization in human atherosclerosis. , 2006, Current molecular medicine.

[62]  D. Baim,et al.  Beyond Restenosis: Five-Year Clinical Outcomes From Second-Generation Coronary Stent Trials , 2004, Circulation.

[63]  P. Serruys,et al.  Characterizing Vulnerable Plaque Features With Intravascular Elastography , 2003, Circulation.

[64]  V. Fuster,et al.  Effects of Lipid-Lowering by Simvastatin on Human Atherosclerotic Lesions: A Longitudinal Study by High-Resolution, Noninvasive Magnetic Resonance Imaging , 2001, Circulation.

[65]  Sharon-Lise T. Normand,et al.  Coronary Artery Spatial Distribution of Acute Myocardial Infarction Occlusions , 2004, Circulation.

[66]  S. Nissen.  The vulnerable plaque "hypothesis": promise, but little progress. , 2009, JACC. Cardiovascular imaging.

[67]  V. Fuster,et al.  Identification of interleukin-2 for imaging atherosclerotic inflammation , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[68]  Frits Mastik,et al.  Intravascular palpography for vulnerable plaque assessment. , 2006, Journal of the American College of Cardiology.

[69]  Raimund Erbel,et al.  Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. , 2006, JAMA.

[70]  V. Fuster,et al.  Promoting mechanisms of vascular health: circulating progenitor cells, angiogenesis, and reverse cholesterol transport. , 2009, Journal of the American College of Cardiology.

[71]  M. Daemen,et al.  The vulnerable patient: Refocusing on the plaque? , 2009, Thrombosis and Haemostasis.

[72]  V. Fuster,et al.  Integration of vascular biology and magnetic resonance imaging in the understanding of atherothrombosis and acute coronary syndromes , 2003, Journal of thrombosis and haemostasis : JTH.

[73]  Christopher P Cannon,et al.  Intensive versus moderate lipid lowering with statins after acute coronary syndromes. , 2004, The New England journal of medicine.

[74]  M J Davies,et al.  Relation of plaque lipid composition and morphology to the stability of human aortic plaques. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[75]  Darío Echeverri,et al.  Reparação vascular após implante de stents não-farmacológicos e farmacológicos em modelo experimental de fibroateroma de capa fina em coelhos , 2008 .

[76]  U. Goldbourt,et al.  Relation between on-treatment increments in serum high-density lipoprotein cholesterol levels and cardiac mortality in patients with coronary heart disease (from the Bezafibrate Infarction Prevention trial). , 2006, The American journal of cardiology.

[77]  P. Weissberg,et al.  Radionuclide imaging for the detection of inflammation in vulnerable plaques. , 2006, Journal of the American College of Cardiology.

[78]  Lev Muchnik,et al.  Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aortas and in situ coronary arteries. , 2005, Journal of the American College of Cardiology.

[79]  P. Moreno,et al.  Detection of Lipid Pool, Thin Fibrous Cap, and Inflammatory Cells in Human Aortic Atherosclerotic Plaques by Near-Infrared Spectroscopy , 2002, Circulation.

[80]  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.

[81]  R. Virmani,et al.  Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. , 2006, Journal of the American College of Cardiology.

[82]  Davies Mj.  Pathophysiology of acute coronary syndromes. , 2000, Indian heart journal.

[83]  P. Serruys,et al.  The Vulnerable Plaque , 2007 .

[84]  P. Serruys,et al.  Coronary plaque composition of nonculprit lesions, assessed by in vivo intracoronary ultrasound radio frequency data analysis, is related to clinical presentation. , 2006, American heart journal.

[85]  H Rijsterborgh,et al.  Histopathologic validation of intracoronary ultrasound imaging. , 1994, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[86]  I. Hochberg,et al.  Haptoglobin phenotype and vascular complications in patients with diabetes. , 2000, The New England journal of medicine.

[87]  H. Fujita,et al.  Assessment of vulnerable plaques causing acute coronary syndrome using integrated backscatter intravascular ultrasound. , 2006, Journal of the American College of Cardiology.

[88]  Zahi A Fayad,et al.  Plaque imaging and characterization using magnetic resonance imaging: towards molecular assessment. , 2006, Current molecular medicine.

[89]  W. Laskey,et al.  Clinical Progression of Incidental, Asymptomatic Lesions Discovered During Culprit Vessel Coronary Intervention , 2005, Circulation.

[90]  Marco Valgimigli,et al.  In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis. , 2005, Journal of the American College of Cardiology.

[91]  Nico de Jong,et al.  Contrast Harmonic Intravascular Ultrasound: A Feasibility Study for Vasa Vasorum Imaging , 2006, Investigative radiology.

[92]  Z. Fayad,et al.  Advances in detection and characterization of atherosclerosis using contrast agents targeting the macrophage , 2006, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[93]  C von Birgelen,et al.  Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound , 1999, Heart.

[94]  J. Ambrose,et al.  Classification of systemic therapies for potential stabilization of the vulnerable plaque to prevent acute myocardial infarction. , 2005, The American journal of cardiology.

[95]  Nicusor Iftimia,et al.  Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. , 2004, Journal of the American College of Cardiology.

[96]  Samuel A. Wickline,et al.  Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With &agr;v&bgr;3-Integrin–Targeted Nanoparticles , 2003 .

[97]  Young-Hak Kim,et al.  Effects of statin treatments on coronary plaques assessed by volumetric virtual histology intravascular ultrasound analysis. , 2009, JACC. Cardiovascular interventions.

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

[99]  G. Puppini,et al.  Characterisation of carotid atherosclerotic plaque: comparison between magnetic resonance imaging and histology , 2006, La radiologia medica.

[100]  A. Levy,et al.  Haptoglobin Genotype– and Diabetes-Dependent Differences in Iron-Mediated Oxidative Stress In Vitro and In Vivo , 2005, Circulation research.

[101]  J. Pickard,et al.  Imaging Atherosclerotic Plaque Inflammation With [18F]-Fluorodeoxyglucose Positron Emission Tomography , 2002, Circulation.

[102]  A. Kastrati,et al.  Haptoglobin Genotype Is Predictive of Major Adverse Cardiac Events in the 1-year Period after Percutaneous Transluminal Coronary Angioplasty in Individuals with Diabetes , 2022 .

[103]  V. Fuster,et al.  MRI to detect atherosclerosis with gadolinium‐containing immunomicelles targeting the macrophage scavenger receptor , 2006, Magnetic resonance in medicine.

[104]  Hirofumi Anno,et al.  Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. , 2009, Journal of the American College of Cardiology.

[105]  Renu Virmani,et al.  Morphological Predictors of Arterial Remodeling in Coronary Atherosclerosis , 2002, Circulation.

[106]  R. Virmani,et al.  Pathology of the Vulnerable Plaque , 2006 .

[107]  V. Fuster,et al.  Caspase-3 and Tissue Factor Expression in Lipid-Rich Plaque Macrophages: Evidence for Apoptosis as Link Between Inflammation and Atherothrombosis , 2004, Circulation.

[108]  Oliver Mf,et al.  The atheromatous lipid core. , 1998 .

[109]  R D Kamm,et al.  Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. , 1992, Circulation research.

[110]  R. Pakala,et al.  Intracoronary photodynamic therapy reduces neointimal growth without suppressing re-endothelialisation in a porcine model , 2006, Heart.

[111]  J. Granada,et al.  Vulnerable plaque paradigm: Prediction of future clinical events based on a morphological definition , 2004, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[112]  C. Zarins,et al.  Compensatory enlargement of human atherosclerotic coronary arteries. , 1987, The New England journal of medicine.

[113]  C. Alpers,et al.  Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. , 1996, Circulation.

[114]  Seung‐Jung Park,et al.  Impact of plaque characteristics analyzed by intravascular ultrasound on long-term clinical outcomes. , 2009, American Journal of Cardiology.

[115]  E. Braunwald.  Noninvasive detection of vulnerable coronary plaques: Locking the barn door before the horse is stolen. , 2009, Journal of the American College of Cardiology.

[116]  H. Fujita,et al.  Association of coronary plaque composition and arterial remodelling: a virtual histology analysis by intravascular ultrasound , 2006, Heart.

[117]  Ralph Weissleder,et al.  Molecular and cellular imaging of atherosclerosis: emerging applications. , 2006, Journal of the American College of Cardiology.

[118]  S E Nissen,et al.  Extent and direction of arterial remodeling in stable versus unstable coronary syndromes : an intravascular ultrasound study. , 2000, Circulation.

[119]  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.

[120]  A. Tedgui,et al.  Role of matrix metalloproteinases in blood flow-induced arterial enlargement: interaction with NO. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[121]  M. Hori,et al.  Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. , 2001, Journal of the American College of Cardiology.

[122]  M. Simons.  Angiogenesis: where do we stand now? , 2005, Circulation.

[123]  Jagat Narula,et al.  Imaging vulnerable plaque by ultrasound. , 2006, Journal of the American College of Cardiology.

[124]  M. Ferguson,et al.  Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. , 1993, The Journal of clinical investigation.

[125]  Brett E Bouma,et al.  Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques. , 2006, Journal of the American College of Cardiology.

[126]  M. Davies.  The pathophysiology of acute coronary syndromes , 2000, Indian heart journal.

[127]  Endovascular Cryotherapy Accentuates the Accumulation of the Fibrillar Collagen Types I and III after Percutaneous Transluminal Angioplasty in Pigs , 2006, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[128]  V. Fuster,et al.  Atherosclerosis neovascularization and imaging. , 2006, Current molecular medicine.

[129]  V. Fuster,et al.  Intimomedial Interface Damage and Adventitial Inflammation Is Increased Beneath Disrupted Atherosclerosis in the Aorta: Implications for Plaque Vulnerability , 2002, Circulation.

[130]  Zahi A Fayad,et al.  Atherothrombosis and high-risk plaque: part I: evolving concepts. , 2005, Journal of the American College of Cardiology.

[131]  M. Davies,et al.  Relationship Between Coronary Artery Remodeling and Plaque Vulnerability , 2002, Circulation.

[132]  A F van der Steen,et al.  Intravascular ultrasound combined with Raman spectroscopy to localize and quantify cholesterol and calcium salts in atherosclerotic coronary arteries. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[133]  E. Tuzcu,et al.  Coronary arterial remodeling: From bench to bedside , 2003, Current atherosclerosis reports.