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(Circulation. 1995;92:1355-1374.)
© 1995 American Heart Association, Inc.

Articles

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

Herbert C. Stary, MD, CHAIR; A. Bleakley Chandler, MD; Robert E. Dinsmore, MD; Valentin Fuster, MD, PhD; Seymour Glagov, MD; William Insull, Jr, MD; Michael E. Rosenfeld, PhD; Colin J. Schwartz, MD; William D. Wagner, PhD; Robert W. Wissler, PhD, MD

Abstract This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Key Words: atherosclerosis • lesion • AHA Medical/Scientific Statements

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				M. E. Clouse, J. Chen, H. M. Krumholz, M. E. Clouse, J. Chen, and H. M. Krumholz Noninvasive Screening for Coronary Artery Disease With Computed Tomography Is Useful Circulation, January 3, 2006; 113(1): 125 - 146. [Full Text] [PDF]

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				J. Cai, T. S. Hatsukami, M. S. Ferguson, W. S. Kerwin, T. Saam, B. Chu, N. Takaya, N. L. Polissar, and C. Yuan In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque: Comparison of High-Resolution, Contrast-Enhanced Magnetic Resonance Imaging and Histology Circulation, November 29, 2005; 112(22): 3437 - 3444. [Abstract] [Full Text] [PDF]

				M. Sneck, P. T. Kovanen, and K. Oorni Decrease in pH Strongly Enhances Binding of Native, Proteolyzed, Lipolyzed, and Oxidized Low Density Lipoprotein Particles to Human Aortic Proteoglycans J. Biol. Chem., November 11, 2005; 280(45): 37449 - 37454. [Abstract] [Full Text] [PDF]

				E. Pearce, D.-A. Tregouet, A. Samnegard, A. R. Morgan, C. Cox, A. Hamsten, P. Eriksson, and S. Ye Haplotype Effect of the Matrix Metalloproteinase-1 Gene on Risk of Myocardial Infarction Circ. Res., November 11, 2005; 97(10): 1070 - 1076. [Abstract] [Full Text] [PDF]

				J. Y. King, R. Ferrara, R. Tabibiazar, J. M. Spin, M. M. Chen, A. Kuchinsky, A. Vailaya, R. Kincaid, A. Tsalenko, D. X.-F. Deng, et al. Pathway analysis of coronary atherosclerosis Physiol Genomics, September 21, 2005; 23(1): 103 - 118. [Abstract] [Full Text] [PDF]

				V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]

				K. J. Williams and I. Tabas Lipoprotein Retention--and Clues for Atheroma Regression Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1536 - 1540. [Abstract] [Full Text] [PDF]

				A. Repetto, B. D. Bello, M. Pasotti, M. Agozzino, M. Vigano, C. Klersy, L. Tavazzi, and E. Arbustini Coronary atherosclerosis in end-stage idiopathic dilated cardiomyopathy: an innocent bystander? Eur. Heart J., August 1, 2005; 26(15): 1519 - 1527. [Abstract] [Full Text] [PDF]

				L. Djousse, D. K. Arnett, J. J. Carr, J. H. Eckfeldt, P. N. Hopkins, M. A. Province, and R. C. Ellison Dietary Linolenic Acid Is Inversely Associated With Calcified Atherosclerotic Plaque in the Coronary Arteries: The National Heart, Lung, and Blood Institute Family Heart Study Circulation, June 7, 2005; 111(22): 2921 - 2926. [Abstract] [Full Text] [PDF]

				W M Howell, S Ali, M J Rose-Zerilli, and S Ye VEGF polymorphisms and severity of atherosclerosis J. Med. Genet., June 1, 2005; 42(6): 485 - 490. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden The European Association for the Study of Diabetes Diabetes Care, May 1, 2005; 28(5): 1250 - 1257. [Full Text] [PDF]

				L. V. Hofmann, R. P. Liddell, J. Eng, B. A. Wasserman, A. Arepally, D. S. Lee, and D. A. Bluemke Human Peripheral Arteries: Feasibility of Transvenous Intravascular MR Imaging of the Arterial Wall Radiology, May 1, 2005; 235(2): 617 - 622. [Abstract] [Full Text] [PDF]

				I. Cicha, A. Yilmaz, M. Klein, D. Raithel, D. R. Brigstock, W. G. Daniel, M. Goppelt-Struebe, and C. D. Garlichs Connective Tissue Growth Factor Is Overexpressed in Complicated Atherosclerotic Plaques and Induces Mononuclear Cell Chemotaxis In Vitro Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 1008 - 1013. [Abstract] [Full Text] [PDF]

				G. K. Hansson Inflammation, Atherosclerosis, and Coronary Artery Disease N. Engl. J. Med., April 21, 2005; 352(16): 1685 - 1695. [Full Text] [PDF]

				J. Zhou, S. Lhotak, B. A. Hilditch, and R. C. Austin Activation of the Unfolded Protein Response Occurs at All Stages of Atherosclerotic Lesion Development in Apolipoprotein E-Deficient Mice Circulation, April 12, 2005; 111(14): 1814 - 1821. [Abstract] [Full Text] [PDF]

				G Arno, J C Kaski, D A Smith, J P Akiyu, S E Hughes, and C Baboonian Matrix metalloproteinase-9 expression is associated with the presence of Chlamydia pneumoniae in human coronary atherosclerotic plaques Heart, April 1, 2005; 91(4): 521 - 525. [Abstract] [Full Text] [PDF]

				T. Saam, M.S. Ferguson, V.L. Yarnykh, N. Takaya, D. Xu, N.L. Polissar, T.S. Hatsukami, and C. Yuan Quantitative Evaluation of Carotid Plaque Composition by In Vivo MRI Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 234 - 239. [Abstract] [Full Text] [PDF]

				N. Kalinina, A. Agrotis, Y. Antropova, G. DiVitto, P. Kanellakis, G. Kostolias, O. Ilyinskaya, E. Tararak, and A. Bobik Increased Expression of the DNA-Binding Cytokine HMGB1 in Human Atherosclerotic Lesions: Role of Activated Macrophages and Cytokines Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2320 - 2325. [Abstract] [Full Text] [PDF]

				M. A. McAteer, J. E. Schneider, K. Clarke, S. Neubauer, K. M. Channon, and R. P. Choudhury Quantification and 3D Reconstruction of Atherosclerotic Plaque Components in Apolipoprotein E Knockout Mice Using Ex Vivo High-Resolution MRI Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2384 - 2390. [Abstract] [Full Text] [PDF]

				A F Kopp, A Kuttner, T Trabold, M Heuschmid, S Schroder, and C D Claussen Multislice CT in cardiac and coronary angiography Br. J. Radiol., December 1, 2004; 77(suppl_1): S87 - S97. [Abstract] [Full Text] [PDF]

				A. Kampschulte, M.S. Ferguson, W.S. Kerwin, N. L. Polissar, B. Chu, T. Saam, T.S. Hatsukami, and C. Yuan Differentiation of Intraplaque Versus Juxtaluminal Hemorrhage/Thrombus in Advanced Human Carotid Atherosclerotic Lesions by In Vivo Magnetic Resonance Imaging Circulation, November 16, 2004; 110(20): 3239 - 3244. [Abstract] [Full Text] [PDF]