Mechanisms of plaque formation and rupture

Circulation Research

Volumn 114, Issue 12, 2014, Pages 1852-1866

  Bentzon, Jacob Fog ^a,b   Otsuka, Fumiyuki ^c   Virmani, Renu ^c   Falk, Erling ^a,b  

^a Department of Clinical Medicine ^*  (Denmark)

^b AARHUS UNIVERSITY HOSPITAL   (Denmark)

^c CVPATH INSTITUTE   (United States)

Author keywords

Atherosclerosis

Indexed keywords

LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ANGIOCARDIOGRAPHY; ANGIOGENESIS; APOPTOSIS; ARTICLE; ATHEROGENESIS; ATHEROSCLEROTIC PLAQUE; BLEEDING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR PARAMETERS; CARDIOVASCULAR RISK; CELL DEATH; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; CORONARY ARTERY BLOOD FLOW; CORONARY ARTERY CALCIFICATION; CORONARY ARTERY DISEASE; CORONARY ARTERY FIBROSIS; CORONARY ARTERY OCCLUSION; DISEASE ACTIVITY; DISEASE CLASSIFICATION; DISEASE COURSE; DISEASE SEVERITY; HUMAN; HYPERTENSION; INFLAMMATION; INTIMA; INTRAVASCULAR ULTRASOUND; NECROTIC CORE; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; PERIPHERAL VASCULAR DISEASE; PLAQUE BURDEN; PLAQUE RUPTURE; PLAQUE VULNERABILITY; PRIORITY JOURNAL; SMOKING; SMOOTH MUSCLE FIBER; THIN FIBROUS CAP; THROMBOSIS; UNSTABLE ANGINA PECTORIS; VASOSPASM;

ATHEROSCLEROSIS;

ACUTE CORONARY SYNDROME; CORONARY ARTERY DISEASE; HUMANS; PLAQUE, ATHEROSCLEROTIC; RUPTURE, SPONTANEOUS;

EID: 84902131678     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.302721     Document Type: Article

References (146)

1. Levy D. Combating the epidemic of heart disease. JAMA. 2012;308:2624-2625.
2. Murray CJ, Lopez AD. Measuring the global burden of disease. N Engl J Med. 2013;369:448-457.
3. Laslett LJ, Alagona P Jr, Clark BA III, Drozda JP Jr, Saldivar F, Wilson SR, Poe C, Hart M. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: A report from the American College of Cardiology. J Am Coll Cardiol. 2012;60:S1-S49.
4. Fuster V, Mearns BM. The CVD paradox: mortality vs prevalence. Nat Rev Cardiol. 2009;6:669.
5. Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N Engl J Med. 2012;366:54-63.
6. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952.
7. Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224-2260.
8. Steinberg D, Glass CK, Witztum JL. Evidence mandating earlier and more aggressive treatment of hypercholesterolemia. Circulation. 2008;118:672-677.
9. Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams KA, Flack JM. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease. J Am Coll Cardiol. 2012;60:2631-2639.
10. Bøttcher M, Falk E. Pathology of the coronary arteries in smokers and non-smokers. J Cardiovasc Risk. 1999;6:299-302.
11. Go AS, Mozaffarian D, Roger VL, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2014 update: A report from the American Heart Association. Circulation. 2014;129:e28-e292.
12. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis. Lancet. 2013;382:1329-1340.
13. Willey J, Gonzalez-Castellon M. Cholesterol level and stroke: A complex relationship. JAMA Intern Med. 2013;173:1765-1766.
14. Bentzon JF, Falk E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr Opin Lipidol. 2010;21:434-440.
15. Stary HC, Blankenhorn DH, Chandler AB, Glagov S, Insull W Jr, Richardson M, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD. A definition of the intima of human arteries and of its atherosclerosisprone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1992;85:391-405.
16. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1994;14:840-856.
17. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. 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. Circulation. 1995;92:1355-1374.
18. Stary HC. Natural history and histological classification of atherosclerotic lesions: An update. Arterioscler Thromb Vasc Biol. 2000;20: 1177-1178.
19. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: A comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275.
20. Wentzel JJ, Chatzizisis YS, Gijsen FJ, Giannoglou GD, Feldman CL, Stone PH. Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions. Cardiovasc Res. 2012;96:234-243.
21. Millonig G, Niederegger H, Rabl W, Hochleitner BW, Hoefer D, Romani N, Wick G. Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol. 2001;21:503-508.
22. Schwartz SM, deBlois D, OBrien ER. The intima. Soil for atherosclerosis and restenosis. Circ Res. 1995;77:445-465.
23. Velican D, Velican C. Atherosclerotic involvement of the coronary arteries of adolescents and young adults. Atherosclerosis. 1980;36:449-460.
24. Roberts WC. Coronary atherosclerosis: is the process focal or diffuse among patients with symptomatic or fatal myocardial ischemia? Am J Cardiol. 1998;82:41T-44T.
25. Cheng C, Tempel D, van Haperen R, van der Baan A, Grosveld F, Daemen MJ, Krams R, de Crom R. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation. 2006;113:2744-2753.
26. Steinberg D, Witztum JL. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30:2311-2316.
27. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317-325.
28. Subramanian M, Tabas I. Dendritic cells in atherosclerosis. Semin Immunopathol. 2014;36:93-102.
29. Skalén K, Gustafsson M, Rydberg EK, Hultén LM, Wiklund O, Innerarity TL, Borén J. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature. 2002;417:750-754.
30. Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116:1832-1844.
31. Stamler J, Daviglus ML, Garside DB, Dyer AR, Greenland P, Neaton JD. Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and all-cause mortality and to longevity. JAMA. 2000;284:311-318.
32. Hartiala O, Magnussen CG, Kajander S, et al. Adolescence risk factors are predictive of coronary artery calcification at middle age: The cardiovascular risk in young Finns study. J Am Coll Cardiol. 2012;60:1364-1370.
33. Leitinger N, Schulman IG. Phenotypic polarization of macrophages in atherosclerosis. Arterioscler Thromb Vasc Biol. 2013;33:1120-1126.
34. Bouhlel MA, Derudas B, Rigamonti E, Dièvart R, Brozek J, Haulon S, Zawadzki C, Jude B, Torpier G, Marx N, Staels B, Chinetti-Gbaguidi G. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007;6:137-143.
35. Stöger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, Daemen MJ, Lutgens E, de Winther MP. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012;225:461-468.
36. Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol. 2010;10:36-46.
37. Hansson GK, Jonasson L. The discovery of cellular immunity in the atherosclerotic plaque. Arterioscler Thromb Vasc Biol. 2009;29:1714-1717.
38. Hansson GK, Nilsson J. Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin Immunopathol. 2009;31:95-101.
39. Steinberg D. The LDL modification hypothesis of atherogenesis: An update. J Lipid Res. 2009;50(suppl):S376-S381.
40. Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002;277:49982-49988.
41. Haka AS, Grosheva I, Chiang E, Buxbaum AR, Baird BA, Pierini LM, Maxfield FR. Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins. Mol Biol Cell. 2009;20:4932-4940.
42. Witztum JL. You are right too! J Clin Invest. 2005;115:2072-2075.
43. Katsuda S, Boyd HC, Fligner C, Ross R, Gown AM. Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults. Am J Pathol. 1992;140:907-914.
44. Napoli C, DArmiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, Palinski W. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100:2680-2690.
45. Stary HC. Lipid and macrophage accumulations in arteries of children and the development of atherosclerosis. Am J Clin Nutr. 2000;72:1297S-1306S.
46. Kolodgie FD, Burke AP, Nakazawa G, Virmani R. Is pathologic intimal thickening the key to understanding early plaque progression in human atherosclerotic disease? Arterioscler Thromb Vasc Biol. 2007;27:986-989.
47. Dalager S, Paaske WP, Kristensen IB, Laurberg JM, Falk E. Artery-related differences in atherosclerosis expression: implications for atherogenesis and dynamics in intima-media thickness. Stroke. 2007;38:2698-2705.
48. Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med. 2003;349:2316-2325.
49. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341-355.
50. Clarke MC, Bennett MR. Cause or consequence: what does macrophage apoptosis do in atherosclerosis? Arterioscler Thromb Vasc Biol. 2009;29:153-155.
51. Myoishi M, Hao H, Minamino T, Watanabe K, Nishihira K, Hatakeyama K, Asada Y, Okada K, Ishibashi-Ueda H, Gabbiani G, Bochaton-Piallat ML, Mochizuki N, Kitakaze M. Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation. 2007;116:1226-1233.
52. Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M, Feric NT, Koschinsky ML, Harkewicz R, Witztum JL, Tsimikas S, Golenbock D, Moore KJ, Tabas I. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 2010;12:467-482.
53. Lutgens E, de Muinck ED, Kitslaar PJ, Tordoir JH, Wellens HJ, Daemen MJ. Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques. Cardiovasc Res. 1999;41:473-479.
54. Crisby M, Kallin B, Thyberg J, Zhivotovsky B, Orrenius S, Kostulas V, Nilsson J. Cell death in human atherosclerotic plaques involves both oncosis and apoptosis. Atherosclerosis. 1997;130:17-27.
55. Schrijvers DM, De Meyer GR, Kockx MM, Herman AG, Martinet W. Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25:1256-1261.
56. Gautier EL, Huby T, Witztum JL, Ouzilleau B, Miller ER, Saint-Charles F, Aucouturier P, Chapman MJ, Lesnik P. Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage. Circulation. 2009;119:1795-1804.
57. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med. 2006;12:1075-1080.
58. Guyton JR. Phospholipid hydrolytic enzymes in a cesspool of arterial intimal lipoproteins: A mechanism for atherogenic lipid accumulation. Arterioscler Thromb Vasc Biol. 2001;21:884-886.
59. Haka AS, Grosheva I, Singh RK, Maxfield FR. Plasmin promotes foam cell formation by increasing macrophage catabolism of aggregated low-density lipoprotein. Arterioscler Thromb Vasc Biol. 2013;33: 1768-1778.
60. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol. 1997;17:95-106.
61. Kumamoto M, Nakashima Y, Sueishi K. Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol. 1995;26:450-456.
62. Sluimer JC, Kolodgie FD, Bijnens AP, Maxfield K, Pacheco E, Kutys B, Duimel H, Frederik PM, van Hinsbergh VW, Virmani R, Daemen MJ. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J Am Coll Cardiol. 2009;53:1517-1527.
63. Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med. 1984;310:1137-1140.
64. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J. 1983;50:127-134.
65. Finn AV, Nakano M, Polavarapu R, Karmali V, Saeed O, Zhao X, Yazdani S, Otsuka F, Davis T, Habib A, Narula J, Kolodgie FD, Virmani R. Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J Am Coll Cardiol. 2012;59:166-177.
66. Purushothaman M, Krishnan P, Purushothaman KR, Baber U, Tarricone A, Perez JS, Wiley J, Kini A, Sharma SK, Fuster V, Moreno PR. Genotypedependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2769-2775.
67. Cahill LE, Levy AP, Chiuve SE, Jensen MK, Wang H, Shara NM, Blum S, Howard BV, Pai JK, Mukamal KJ, Rexrode KM, Rimm EB. Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin. J Am Coll Cardiol. 2013;61:728-737.
68. Kragel AH, Reddy SG, Wittes JT, Roberts WC. Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death. Circulation. 1989;80:1747-1756.
69. Stary HC. An Atlas of Atherosclerosis: Progression and Regression. New York: Parthenon Publishing Group; 1999.
70. Gomez D, Shankman LS, Nguyen AT, Owens GK. Detection of histone modifications at specific gene loci in single cells in histological sections. Nat Methods. 2013;10:171-177.
71. Bentzon JF, Weile C, Sondergaard CS, Hindkjaer J, Kassem M, Falk E. Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice. Arterioscler Thromb Vasc Biol. 2006;26:2696-2702.
72. Campbell JH, Campbell GR. Smooth muscle phenotypic modulation-A personal experience. Arterioscler Thromb Vasc Biol. 2012;32:1784-1789.
73. Feil S, Hofmann F, Feil R. SM22alpha modulates vascular smooth muscle cell phenotype during atherogenesis. Circ Res. 2004;94:863-865.
74. Tang Z, Wang A, Yuan F, Yan Z, Liu B, Chu JS, Helms JA, Li S. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun. 2012;3:875.
75. Bentzon JF, Falk E. Circulating smooth muscle progenitor cells in atherosclerosis and plaque rupture: current perspective and methods of analysis. Vascul Pharmacol. 2010;52:11-20.
76. Nguyen AT, Gomez D, Bell RD, et al. Smooth muscle cell plasticity: fact or fiction? Circ Res. 2013;112:17-22.
77. Otsuka F, Sakakura K, Yahagi K, Joner M, Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler Thromb Vasc Biol. 2014;34:724-736.
78. Stary HC. The development of calcium deposits in atherosclerotic lesions and their persistence after lipid regression. Am J Cardiol. 2001;88:16E-19E.
79. Qiao JH, Fishbein MC, Demer LL, Lusis AJ. Genetic determination of cartilaginous metaplasia in mouse aorta. Arterioscler Thromb Vasc Biol. 1995;15:2265-2272.
80. Otsuka F, Finn AV, Virmani R. Do vulnerable and ruptured plaques hide in heavily calcified arteries? Atherosclerosis. 2013;229:34-37.
81. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316:1371-1375.
82. Nishioka T, Luo H, Eigler NL, Berglund H, Kim CJ, Siegel RJ. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: An in vivo intravascular ultrasound study. J Am Coll Cardiol. 1996;27:1571-1576.
83. Varnava AM, Mills PG, Davies MJ. Relationship between coronary artery remodeling and plaque vulnerability. Circulation. 2002;105:939-943.
84. Burke AP, Kolodgie FD, Farb A, Weber D, Virmani R. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation. 2002;105:297-303.
85. Davies MJ. The pathophysiology of acute coronary syndromes. Heart. 2000;83:361-366.
86. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657-671.
87. Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, Colombo A, Stefanadis C, Ward Casscells S, Moreno PR, Maseri A, van der Steen AF. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J. 2004;25:1077-1082.
88. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: The pathologists view. Eur Heart J. 2013;34:719-728.
89. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T. 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;50:933-939.
90. Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation. 1998;97:2110-2116.
91. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med. 1997;336:1276-1282.
92. Jia H, Abtahian F, Aguirre AD, et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J Am Coll Cardiol. 2013;62:1748-1758.
93. Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, Finn AV, Virmani R. The thin-cap fibroatheroma: A type of vulnerable plaque: The major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001;16:285-292.
94. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation. 1994;89:36-44.
95. Gough PJ, Gomez IG, Wille PT, Raines EW. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest. 2006;116:59-69.
96. Mittleman MA, Mostofsky E. Physical, psychological and chemical triggers of acute cardiovascular events: preventive strategies. Circulation. 2011;124:346-354.
97. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985;313:1315-1322.
98. Martin JF, Kristensen SD, Mathur A, Grove EL, Choudry FA. The causal role of megakaryocyte-platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol. 2012;9:658-670.
99. Kloner RA, Leor J, Poole WK, Perritt R. Population-based analysis of the effect of the Northridge Earthquake on cardiac death in Los Angeles County, California. J Am Coll Cardiol. 1997;30:1174-1180.
100. Kramer MC, Rittersma SZ, de Winter RJ, Ladich ER, Fowler DR, Liang YH, Kutys R, Carter-Monroe N, Kolodgie FD, van der Wal AC, Virmani R. Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J Am Coll Cardiol. 2010;55:122-132.
101. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13-C18.
102. Hao H, Gabbiani G, Camenzind E, Bacchetta M, Virmani R, Bochaton-Piallat ML. Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesion. Arterioscler Thromb Vasc Biol. 2006;26:326-332.
103. Davies MJ, Bland JM, Hangartner JR, Angelini A, Thomas AC. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J. 1989;10:203-208.
104. Mann J, Davies MJ. Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart. 1999;82:265-268.
105. Burke AP, Kolodgie FD, Farb A, Weber DK, Malcom GT, Smialek J, Virmani R. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation. 2001;103:934-940.
106. Barua RS, Ambrose JA. Mechanisms of coronary thrombosis in cigarette smoke exposure. Arterioscler Thromb Vasc Biol. 2013;33:1460-1467.
107. Fernández-Ortiz A, Badimon JJ, Falk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK, Badimon L. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol. 1994; 23:1562-1569.
108. Rautou PE, Vion AC, Amabile N, Chironi G, Simon A, Tedgui A, Boulanger CM. Microparticles, vascular function, and atherothrombosis. Circ Res. 2011;109:593-606.
109. 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;71:699-708.
110. Rittersma SZ, van der Wal AC, Koch KT, Piek JJ, Henriques JP, Mulder KJ, Ploegmakers JP, Meesterman M, de Winter RJ. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: A pathological thrombectomy study in primary percutaneous coronary intervention. Circulation. 2005;111:1160-1165.
111. Wakefield TW, Strieter RM, Wilke CA, Kadell AM, Wrobleski SK, Burdick MD, Schmidt R, Kunkel SL, Greenfield LJ. Venous thrombosisassociated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol. 1995;15:258-268.
112. Falk E, Thuesen L. Pathology of coronary microembolisation and no reflow. Heart. 2003;89:983-985.
113. Schwartz RS, Burke A, Farb A, Kaye D, Lesser JR, Henry TD, Virmani R. Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary death: relation to epicardial plaque histopathology. J Am Coll Cardiol. 2009;54:2167-2173.
114. Yee KO, Schwartz SM. Why atherosclerotic vessels narrow: The fibrin hypothesis. Thromb Haemost. 1999;82:762-771.
115. Bruschke AV, Kramer JR Jr, Bal ET, Haque IU, Detrano RC, Goormastic M. The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J. 1989;117:296-305.
116. Dalager S, Falk E, Kristensen IB, Paaske WP. Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: An autopsy study. J Vasc Surg. 2008;47:296-302.
117. Otsuka F, Fuster V, Narula J, Virmani R. Omnipresent atherosclerotic disease: Time to depart from analysis of individual vascular beds. Mt Sinai J Med. 2012;79:641-653.
118. Sillesen H, Muntendam P, Adourian A, Entrekin R, Garcia M, Falk E, Fuster V. Carotid plaque burden as a measure of subclinical atherosclerosis: comparison with other tests for subclinical arterial disease in the High Risk Plaque BioImage study. J Am Coll Cardiol Cardiovasc Imaging. 2012;5:681-689.
119. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.
120. Gonalves I, Stenström K, Skog G, Mattsson S, Nitulescu M, Nilsson J. Short communication: dating components of human atherosclerotic plaques. Circ Res. 2010;106:1174-1177.
121. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365:2078-2087.
122. Kini AS, Baber U, Kovacic JC, Limaye A, Ali ZA, Sweeny J, Maehara A, Mehran R, Dangas G, Mintz GS, Fuster V, Narula J, Sharma SK, Moreno PR. Changes in plaque lipid content after short-term intensive versus standard statin therapy: The YELLOW trial (reduction in yellow plaque by aggressive lipid-lowering therapy). J Am Coll Cardiol. 2013;62:21-29.
123. Björkegren JL, Hägg S, Talukdar HA, Foroughi Asl H, Jain RK, Cedergren C, Shang MM, Rossignoli A, Takolander R, Melander O, Hamsten A, Michoel T, Skogsberg J. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis. PLoS Genet. 2014;10:e1004201.
124. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47:C7-C12.
125. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: A call for new definitions and risk assessment strategies: Part I. Circulation. 2003;108:1664-1672.
126. Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110:278-284.
127. Cheruvu PK, Finn AV, Gardner C, Caplan J, Goldstein J, Stone GW, Virmani R, Muller JE. Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: A pathologic study. J Am Coll Cardiol. 2007;50:940-949.
128. Mauriello A, Sangiorgi G, Fratoni S, Palmieri G, Bonanno E, Anemona L, Schwartz RS, Spagnoli LG. 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. 2005;45:1585-1593.
129. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys PW; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226-235.
130. 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;55:1590-1597.
131. Thim T, Hagensen MK, Wallace-Bradley D, Granada JF, Kaluza GL, Drouet L, Paaske WP, Bøtker HE, Falk E. Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease. Circ Cardiovasc Imaging. 2010;3:384-391.
132. Falk E, Wilensky RL. Prediction of coronary events by intravascular imaging. J Am Coll Cardiol Cardiovasc Imaging. 2012;5:S38-S41.
133. Dohi T, Mintz GS, McPherson JA, de Bruyne B, Farhat NZ, Lansky AJ, Mehran R, Weisz G, Xu K, Stone GW, Maehara A. Non-fibroatheroma lesion phenotype and long-term clinical outcomes. J Am Coll Cardiol Cardiovasc Imaging. 2013;6:908-916.
134. Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques. Am J Cardiol. 1990;66:1368-1372.
135. Fishbein MC, Siegel RJ. How big are coronary atherosclerotic plaques that rupture? Circulation. 1996;94:2662-2666.
136. Bezerra HG, Higuchi ML, Gutierrez PS, Palomino SA, Silvestre JM, Libby P, Ramires JA. Atheromas that cause fatal thrombosis are usually large and frequently accompanied by vessel enlargement. Cardiovasc Pathol. 2001;10:189-196.
137. Puri R, Nicholls SJ, Ellis SG, Tuzcu EM, Kapadia SR. High-risk coronary atheroma-The interplay between ischemia, plaque burden and disease progression. J Am Coll Cardiol. 2014;63:1134-1140.
138. Niccoli G, Stefanini GG, Capodanno D, Crea F, Ambrose JA, Berg R. Are the culprit lesions severely stenotic? J Am Coll Cardiol Cardiovasc Imaging. 2013;6:1108-1114.
139. Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, Malik S, Fuster V, Finn AV. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61:1041-1051.
140. Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J. Atherosclerotic plaque progression and vulnerability to rupture: Angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol. 2005;25:2054-2061.
141. Kohchi K, Takebayashi S, Hiroki T, Nobuyoshi M. Significance of adventitial inflammation of the coronary artery in patients with unstable angina: results at autopsy. Circulation. 1985;71:709-716.
142. Ehara S, Kobayashi Y, Yoshiyama M, Shimada K, Shimada Y, Fukuda D, Nakamura Y, Yamashita H, Yamagishi H, Takeuchi K, Naruko T, Haze K, Becker AE, Yoshikawa J, Ueda M. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: An intravascular ultrasound study. Circulation. 2004;110:3424-3429.
143. Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157:111. e2-117.e2.
144. Sillesen H, Falk E. Why not screen for subclinical atherosclerosis? Lancet. 2011;378:645-646.
145. Grundy SM. Treatment targets in the management of dyslipidemias: which targets in whom? Curr Cardiol Rep. 2012;14:692-700.
146. Webber BJ, Seguin PG, Burnett DG, Clark LL, Otto JL. Prevalence of and risk factors for autopsy-determined atherosclerosis among US service members, 2001-2011. JAMA. 2012;308:2577-2583.