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(Circulation. 2003;108:1772.)
© 2003 American Heart Association, Inc.

Review: Current Perspective

From Vulnerable Plaque to Vulnerable Patient

A Call for New Definitions and Risk Assessment Strategies: Part II

Morteza Naghavi, MD; Peter Libby, MD; Erling Falk, MD, PhD; S. Ward Casscells, MD; Silvio Litovsky, MD; John Rumberger, MD; Juan Jose Badimon, PhD; Christodoulos Stefanadis, MD; Pedro Moreno, MD; Gerard Pasterkamp, MD, PhD; Zahi Fayad, PhD; Peter H. Stone, MD; Sergio Waxman, MD; Paolo Raggi, MD; Mohammad Madjid, MD; Alireza Zarrabi, MD; Allen Burke, MD; Chun Yuan, PhD; Peter J. Fitzgerald, MD, PhD; David S. Siscovick, MD; Chris L. de Korte, PhD; Masanori Aikawa, MD, PhD; K. E. Juhani Airaksinen, MD; Gerd Assmann, MD; Christoph R. Becker, MD; James H. Chesebro, MD; Andrew Farb, MD; Zorina S. Galis, PhD; Chris Jackson, PhD; Ik-Kyung Jang, MD, PhD; Wolfgang Koenig, MD, PhD; Robert A. Lodder, PhD; Keith March, MD, PhD; Jasenka Demirovic, MD, PhD; Mohamad Navab, PhD; Silvia G. Priori, MD, PhD; Mark D. Rekhter, PhD; Raymond Bahr, MD; Scott M. Grundy, MD, PhD; Roxana Mehran, MD; Antonio Colombo, MD; Eric Boerwinkle, PhD; Christie Ballantyne, MD; William Insull, Jr, MD; Robert S. Schwartz, MD; Robert Vogel, MD; Patrick W. Serruys, MD, PhD; Goran K. Hansson, MD, PhD; David P. Faxon, MD; Sanjay Kaul, MD; Helmut Drexler, MD; Philip Greenland, MD; James E. Muller, MD; Renu Virmani, MD; Paul M Ridker, MD; Douglas P. Zipes, MD; Prediman K. Shah, MD; James T. Willerson, MD

From The Center for Vulnerable Plaque Research, University of Texas—Houston, The Texas Heart Institute, and President Bush Center for Cardiovascular Health, Memorial Hermann Hospital, Houston (M. Naghavi, S.W.C., S.L., M.M., A.Z., J.T.W.); The Leducq Center for Cardiovascular Research, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (P.L., M.A.); Department of Cardiology and Institute of Experimental Clinical Research, Aarhus University, Aarhus, Denmark (E.F.); Experimental Cardiology Laboratory, Vascular Biology of the University Medical Center in Utrecht, the Netherlands (G.P.); Ohio State University (J.R.); the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, NY (Z.F.); Cardiac Catheterization Laboratory at the VA Medical Center, University of Kentucky, Lexington (P.M.); Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (P.H.S.); Division of Cardiology, New England Medical Center, Boston, Mass (S.W.); Department of Medicine, Section of Cardiology, Tulane University School of Medicine, New Orleans, La (P.R.); Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC (A.B., A.F., R.V.); Department of Radiology, University of Washington, Seattle (C.Y.); Stanford University Medical Center Stanford, Calif (P.J.F.); Cardiovascular Health Research Unit, University of Washington, Seattle (D.S.S.); Department of Cardiology, Athens Medical School, Athens, Greece (C.S.); Catheterization Laboratory, Thorax Center, Erasmus University, Rotterdam, the Netherlands (C.L.d.K.); Division of Cardiology, Department of Medicine, University of Turku, Finland (K.E.J.A.); Institute of Arteriosclerosis Research and the Institute of Clinical Chemistry and Laboratory Medicine, Central Laboratory, Hospital of the University of Münster, Munich, Germany (G.A.); Department of Clinical Radiology, University of Münster, Munich, Germany (C.R.B.); Mayo Clinic Medical School, Jacksonville, Fla (J.H.C.); Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (Z.S.G.); Bristol Heart Institute, Bristol University, Bristol, United Kingdom (C.J.); Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (I.-K.J.); Department of Internal Medicine II, Cardiology, University of Ulm, Ulm, Germany (W.K.); University of Kentucky, Lexington, Ky (R.A.L.); R.L. Roudebush VA Medical Center, Indianapolis, Ind (K.M.); School of Public Health, University of Texas—Houston, Houston, Texas (J.D.); Division of Cardiology, University of California Los Angeles, Los Angeles, Calif (M. Navab); Fondazione Salvatore Maugeri, University of Pavia, Pavia, Italy (S.G.P.); Department of Cardiovascular Therapeutics, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Mich (M.D.R.); Paul Dudley White Coronary Care System at St. Agnes HealthCare, Baltimore, Md (R.B.); Center for Human Nutrition, University of Texas Health Science Center, Dallas (S.M.G.); Lenox Hill Hospital, New York, NY (R.M.); Catheterization Laboratories, Ospedale San Raffaele and Emo Centro Cuore Columbus, Milan, Italy (A.C.); Human Genetics Center, Institute of Molecular Medicine, Houston, Tex (E.B.); Department of Medicine, Baylor College of Medicine, Houston, Tex (C.B., W.I.); Minneapolis Heart Institute and Foundation, Minneapolis, Minn (R.S.S.); Division of Cardiology, University of Maryland School of Medicine, Baltimore, Md (R.V.); Karolinska Institute, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden (G.K.H.); Section of Cardiology, University of Chicago, Ill (D.P.F.); Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, California (S.K.); Cardiology Department, Hannover University, Hannover, Germany (H.D.); Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill (P.G.); UCLA School of Medicine and Cedars-Sinai Medical Center, Los Angeles, Calif (P.K.S.); Massachusetts General Hospital, Harvard Medical School and CIMIT (Center for Integration of Medicine and Innovative Technology), Boston, Mass (J.E.M.); Cardiovascular Division, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Mass (P.M.R.); and Indiana University School of Medicine, Krannert Institute of Cardiology, Indianapolis (D.P.Z.).

Correspondence to Morteza Naghavi, MD, Association for Eradication of Heart Attack, P.O. Box 20345, Houston, TX 77225-0345. E-mail mn{at}vp.org

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Key Words: coronary disease • plaque • myocardial infarction • atherosclerosis • death, sudden

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				G Parodi, G Memisha, R Valenti, M Trapani, A Migliorini, G M Santoro, and D Antoniucci Five year outcome after primary coronary intervention for acute ST elevation myocardial infarction: results from a single centre experience Heart, December 1, 2005; 91(12): 1541 - 1544. [Abstract] [Full Text] [PDF]

				P. Raggi, A. Bellasi, and C. Ratti Ischemia Imaging and Plaque Imaging in Diabetes: Complementary tools to improve cardiovascular risk management Diabetes Care, November 1, 2005; 28(11): 2787 - 2794. [Abstract] [Full Text] [PDF]

				E. Larose, Y. Yeghiazarians, P. Libby, E.K. Yucel, M. Aikawa, D. F. Kacher, E. Aikawa, S. Kinlay, F. J. Schoen, A. P. Selwyn, et al. Characterization of Human Atherosclerotic Plaques by Intravascular Magnetic Resonance Imaging Circulation, October 11, 2005; 112(15): 2324 - 2331. [Abstract] [Full Text] [PDF]

				S. Sabeti, M. Exner, W. Mlekusch, J. Amighi, P. Quehenberger, H. Rumpold, G. Maurer, E. Minar, O. Wagner, and M. Schillinger Prognostic Impact of Fibrinogen in Carotid Atherosclerosis: Nonspecific Indicator of Inflammation or Independent Predictor of Disease Progression? Stroke, July 1, 2005; 36(7): 1400 - 1404. [Abstract] [Full Text] [PDF]

				P. Libby and P. Theroux Pathophysiology of Coronary Artery Disease Circulation, June 28, 2005; 111(25): 3481 - 3488. [Abstract] [Full Text] [PDF]

				A. Mauriello, G. Sangiorgi, S. Fratoni, G. Palmieri, E. Bonanno, L. Anemona, R. S. Schwartz, and L. G. Spagnoli Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree: A Histopathologic Study of Patients Dying of Acute Myocardial Infarction J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1585 - 1593. [Abstract] [Full Text] [PDF]

				F. S. Apple, A. H.B. Wu, J. Mair, J. Ravkilde, M. Panteghini, J. Tate, F. Pagani, R. H. Christenson, M. Mockel, O. Danne, et al. Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome Clin. Chem., May 1, 2005; 51(5): 810 - 824. [Abstract] [Full Text] [PDF]

				P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF]

				W. Maier, L. A. Altwegg, R. Corti, S. Gay, M. Hersberger, F. E. Maly, G. Sutsch, M. Roffi, M. Neidhart, F. R. Eberli, et al. Inflammatory Markers at the Site of Ruptured Plaque in Acute Myocardial Infarction: Locally Increased Interleukin-6 and Serum Amyloid A but Decreased C-Reactive Protein Circulation, March 22, 2005; 111(11): 1355 - 1361. [Abstract] [Full Text] [PDF]

				K. Y Stokes and D. N. Granger The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia? J. Physiol., February 1, 2005; 562(3): 647 - 653. [Abstract] [Full Text] [PDF]

				A. Lerman and A. M. Zeiher Endothelial Function: Cardiac Events Circulation, January 25, 2005; 111(3): 363 - 368. [Full Text] [PDF]

				S Schroeder, A Kuettner, T Wojak, J Janzen, M Heuschmid, T Athanasiou, T Beck, C Burgstahler, C Herdeg, C D Claussen, et al. Non-invasive evaluation of atherosclerosis with contrast enhanced 16 slice spiral computed tomography: results of ex vivo investigations Heart, December 1, 2004; 90(12): 1471 - 1475. [Abstract] [Full Text] [PDF]

				N. R. Veillard, S. Steffens, F. Burger, G. Pelli, and F. Mach Differential Expression Patterns of Proinflammatory and Antiinflammatory Mediators During Atherogenesis in Mice Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2339 - 2344. [Abstract] [Full Text] [PDF]

				M. Fleiner, M. Kummer, M. Mirlacher, G. Sauter, G. Cathomas, R. Krapf, and B. C. Biedermann Arterial Neovascularization and Inflammation in Vulnerable Patients: Early and Late Signs of Symptomatic Atherosclerosis Circulation, November 2, 2004; 110(18): 2843 - 2850. [Abstract] [Full Text] [PDF]

				I. F. Charo and M. B. Taubman Chemokines in the Pathogenesis of Vascular Disease Circ. Res., October 29, 2004; 95(9): 858 - 866. [Abstract] [Full Text] [PDF]

				L. G. Spagnoli, A. Mauriello, G. Sangiorgi, S. Fratoni, E. Bonanno, R. S. Schwartz, D. G. Piepgras, R. Pistolese, A. Ippoliti, and D. R. Holmes Jr Extracranial Thrombotically Active Carotid Plaque as a Risk Factor for Ischemic Stroke JAMA, October 20, 2004; 292(15): 1845 - 1852. [Abstract] [Full Text] [PDF]

				J. F. Viles-Gonzalez, M. Poon, J. Sanz, T. Rius, K. Nikolaou, Z. A. Fayad, V. Fuster, and J. J. Badimon In Vivo 16-Slice, Multidetector-Row Computed Tomography for the Assessment of Experimental Atherosclerosis: Comparison With Magnetic Resonance Imaging and Histopathology Circulation, September 14, 2004; 110(11): 1467 - 1472. [Abstract] [Full Text] [PDF]

				R. J. Chilton Pathophysiology of Coronary Heart Disease: A Brief Review J Am Osteopath Assoc, September 1, 2004; 104(9_suppl): 5S - 8S. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				J. C. Wang, S.-L. T. Normand, L. Mauri, and R. E. Kuntz Coronary Artery Spatial Distribution of Acute Myocardial Infarction Occlusions Circulation, July 20, 2004; 110(3): 278 - 284. [Abstract] [Full Text] [PDF]

				P. Irimia, E. Martinez-Vila, J. R. Lynch, and D. T. Laskowitz Diagnostic Test for Acute Cerebral Ischemia * Panel of Serum Markers for Rapid Diagnosis of Acute Stroke Stroke, June 1, 2004; 35(6): e140 - e141. [Full Text] [PDF]