Skip to main content
SpringerLink
Log in

Pathology of Vulnerability Caused by High-Risk (Vulnerable) Arteries and Plaques

  • Chapter
  • First Online:
Book cover Asymptomatic Atherosclerosis

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Atherosclerosis is a slowly progressing systemic (multifocal) arterial disease with focal manifestations caused by one or relatively few stenotic and/or thrombosis-prone (vulnerable) plaques. The coronary arteries, carotid arteries, ilio-femoral arteries, and aorta are especially susceptible to atherosclerosis. The most devastating consequences of atherosclerosis, such as heart attack and stroke, are usually caused by thrombosis precipitated by plaque rupture. Although the morphology of ruptured plaques has been known for decades, it remains poorly understood why a single plaque among many plaques becomes vulnerable and suddenly ruptures. Plaque rupture requires the presence of a lipid-rich (necrotic) core covered by a thin fibrous cap, and the development and detection of “core and cap” are currently explored in basic and clinical research. Other plaque and plaque-related features may be useful markers of vulnerability, including plaque inflammation (macrophage density and activity), neovascularization (angiogenesis), hemorrhage, microcalcification, adventitial inflammation (lymphocytes), and expansive remodeling. Vascular imaging and function testing have the potential to provide a comprehensive assessment of atherosclerosis, including detection of plaque burden, plaque vulnerability, and disease activity. The search for better markers of cardiovascular risk must continue. With the traditional risk-factor-based approach in primary prevention, most individuals destined for a near-term heart attack or stroke are misclassified and not identified as being at high risk. Consequently, they are not offered appropriate preventive therapy. Detection of subclinical but high-risk atherosclerosis may change this unfortunate situation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Roberts WC. Diffuse extent of coronary atherosclerosis in fatal coronary artery disease. Am J Cardiol. 1990;65:2F–6F.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–952.

    Article  PubMed  Google Scholar 

  4. Wald NJ, Hackshaw AK, Frost CD. When can a risk factor be used as a worthwhile screening test? BMJ. 1999;319:1562–1565.

    Article  PubMed  CAS  Google Scholar 

  5. Wald NJ, Morris JK, Rish S. The efficacy of combining several risk factors as a screening test. J Med Screen. 2005;12:197–201.

    Article  PubMed  Google Scholar 

  6. Ware JH. The limitations of risk factors as prognostic tools. N Engl J Med. 2006;355:2615–2617.

    Article  PubMed  CAS  Google Scholar 

  7. Lauer MS. Primary prevention of atherosclerotic cardiovascular disease: the high public burden of low individual risk. JAMA. 2007;297:1376–1378.

    Article  PubMed  CAS  Google Scholar 

  8. Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D, Fayad Z, Budoff MJ, Rumberger J, Naqvi TZ, Shaw LJ, Faergeman O, Cohn J, Bahr R, Koenig W, Demirovic J, Arking D, Herrera VL, Badimon J, Goldstein JA, Rudy Y, Airaksinen J, Schwartz RS, Riley WA, Mendes RA, Douglas P, Shah PK. From vulnerable plaque to vulnerable patient – Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol. 2006;98:2H–15H.

    Article  PubMed  Google Scholar 

  9. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47:C7–12.

    Article  PubMed  CAS  Google Scholar 

  10. Thim T, Hagensen MK, Bentzon JF, Falk E. From vulnerable plaque to atherothrombosis. J Intern Med. 2008;263:506–516.

    Article  PubMed  CAS  Google Scholar 

  11. Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, Colombo A, Stefanadis C, Ward CS, 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.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, Piepgras DG, Pistolese R, Ippoliti A, Holmes DR, Jr. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA. 2004;292:1845–1852.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J. 1999;138:S421–S425.

    Article  PubMed  CAS  Google Scholar 

  16. Davies MJ. The pathophysiology of acute coronary syndromes. Heart. 2000;83:361–366.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. Arbustini E, Dal BB, Morbini P, Burke AP, Bocciarelli M, Specchia G, Virmani R. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart. 1999;82:269–272.

    PubMed  CAS  Google Scholar 

  19. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994;90:775–778.

    Article  PubMed  CAS  Google Scholar 

  20. van der Wal AC, Becker AE, Koch KT, Piek JJ, Teeling P, van der Loos CM, David GK. Clinically stable angina pectoris is not necessarily associated with histologically stable atherosclerotic plaques. Heart. 1996;76:312–316.

    Article  PubMed  Google Scholar 

  21. Gronholdt ML, Nordestgaard BG, Bentzon J, Wiebe BM, Zhou J, Falk E, Sillesen H. Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels. J Vasc Surg. 2002;35:137–145.

    PubMed  Google Scholar 

  22. Schwartz SM, Galis ZS, Rosenfeld ME, Falk E. Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol. 2007;27:705–713.

    Article  PubMed  CAS  Google Scholar 

  23. Kolodgie FD, Burke AP, Skorija KS, Ladich E, Kutys R, Makuria AT, Virmani R. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26:2523–2529.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993;69:377–381.

    Article  PubMed  CAS  Google Scholar 

  26. Felton CV, Crook D, Davies MJ, Oliver MF. Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Arterioscler Thromb Vasc Biol. 1997;17:1337–1345.

    Article  PubMed  CAS  Google Scholar 

  27. Katz SS, Shipley GG, Small DM. Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. J Clin Invest. 1976;58:200–211.

    Article  PubMed  CAS  Google Scholar 

  28. Lundberg B. Chemical composition and physical state of lipid deposits in atherosclerosis. Atherosclerosis. 1985;56:93–110.

    Article  PubMed  CAS  Google Scholar 

  29. 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. Circulation. 1994;89:2462–2478.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Stary HC. Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol. 2000;20:1177–1178.

    Article  PubMed  CAS  Google Scholar 

  32. van der Wal AC, Das PK, Tigges AJ, Becker AE. Macrophage differentiation in atherosclerosis. An in situ immunohistochemical analysis in humans. Am J Pathol. 1992;141:161–168.

    PubMed  Google Scholar 

  33. Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol. 2005;25:2255–2264.

    Article  PubMed  CAS  Google Scholar 

  34. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116:1832–1844.

    Article  PubMed  CAS  Google Scholar 

  35. Tedgui A, Mallat Z. Apoptosis as a determinant of atherothrombosis. Thromb Haemost. 2001;86:420–426.

    PubMed  CAS  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. 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.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. Trostdorf F, Buchkremer M, Harmjanz A, Kablau M, Jander S, Geiger K, Schmitz-Rixen T, Steinmetz H, Sitzer M. Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis. Eur J Vasc Endovasc Surg. 2005;29:528–535

    Article  PubMed  CAS  Google Scholar 

  41. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874.

    Article  PubMed  CAS  Google Scholar 

  42. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–1695.

    Article  PubMed  CAS  Google Scholar 

  43. Schwartz SM, Virmani R, Rosenfeld ME. The good smooth muscle cells in atherosclerosis. Curr Atheroscler Rep. 2000;2:422–429.

    Article  PubMed  CAS  Google Scholar 

  44. Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest. 1995;95:2266–2274.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    Article  PubMed  CAS  Google Scholar 

  46. 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.

    Article  PubMed  CAS  Google Scholar 

  47. 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.

    Article  PubMed  CAS  Google Scholar 

  48. Hoofnagle MH, Thomas JA, Wamhoff BR, Owens GK. Origin of neointimal smooth muscle: we’ve come full circle. Arterioscler Thromb Vasc Biol. 2006;26:2579–2581.

    Article  PubMed  CAS  Google Scholar 

  49. Feil S, Hofmann F, Feil R. SM22alpha modulates vascular smooth muscle cell phenotype during atherogenesis. Circ Res. 2004;94:863–865.

    Article  PubMed  CAS  Google Scholar 

  50. 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.

    Article  PubMed  CAS  Google Scholar 

  51. 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.

    Article  PubMed  CAS  Google Scholar 

  52. Verhoeven BA, Moll FL, Koekkoek JA, van der Wal AC, de Kleijn DP, de Vries JP, Verheijen JH, Velema E, Busser E, Schoneveld A, Virmani R, Pasterkamp G. Statin treatment is not associated with consistent alterations in inflammatory status of carotid atherosclerotic plaques: a retrospective study in 378 patients undergoing carotid endarterectomy. Stroke. 2006;37:2054–2060.

    Article  PubMed  CAS  Google Scholar 

  53. Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE, Hillen B, Borst C. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol. 1998;32:655–662.

    Article  PubMed  CAS  Google Scholar 

  54. McCarthy MJ, Loftus IM, Thompson MM, Jones L, London NJ, Bell PR, Naylor AR, Brindle NP. Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology. J Vasc Surg. 1999;30:261–268.

    Article  PubMed  CAS  Google Scholar 

  55. 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.

    Article  PubMed  CAS  Google Scholar 

  56. Barger AC, Beeuwkes R, III, Lainey LL, Silverman KJ. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med. 1984;310:175–177.

    Article  PubMed  CAS  Google Scholar 

  57. Barger AC, Beeuwkes R, III. Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. Am J Cardiol. 1990;66:41G–43G.

    Article  PubMed  CAS  Google Scholar 

  58. Zhang Y, Cliff WJ, Schoefl GI, Higgins G. Immunohistochemical study of intimal microvessels in coronary atherosclerosis. Am J Pathol. 1993;143:164–172.

    PubMed  CAS  Google Scholar 

  59. Kumamoto M, Nakashima Y, Sueishi K. Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol. 1995;26:450–456.

    Article  PubMed  CAS  Google Scholar 

  60. Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, Ishii T, Iida M, Sueishi K. Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol. 2005;36:330–340.

    Article  PubMed  CAS  Google Scholar 

  61. 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.

    Article  PubMed  CAS  Google Scholar 

  62. Burke AP, Kolodgie FD, Farb A, Weber D, Virmani R. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation. 2002;105:297–303.

    Article  PubMed  Google Scholar 

  63. Shiran A, Mintz GS, Leiboff B, Kent KM, Pichard AD, Satler LF, Kimura T, Nobuyoshi M, Leon MB. Serial volumetric intravascular ultrasound assessment of arterial remodeling in left main coronary artery disease. Am J Cardiol. 1999;83:1427–1432.

    Article  PubMed  CAS  Google Scholar 

  64. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657–671.

    Article  PubMed  CAS  Google Scholar 

  65. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356:1503–1516.

    Article  PubMed  CAS  Google Scholar 

  66. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol. 1998;31:126–133.

    Article  PubMed  CAS  Google Scholar 

  67. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Callister TQ, Raggi P, Berman DS. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860–1870.

    Article  PubMed  Google Scholar 

  68. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P, Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS, Harrington RA, Abrams J, Anderson JL, Bates ER, Grines CL, Hlatky MA, Lichtenberg RC, Lindner JR, Pohost GM, Schofield RS, Shubrooks SJ, Jr., Stein JH, Tracy CM, Vogel RA, Wesley DJ. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography). Circulation. 2007;115:402–426.

    Article  PubMed  Google Scholar 

  69. 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.

    Article  PubMed  Google Scholar 

  70. Beckman JA, Ganz J, Creager MA, Ganz P, Kinlay S. Relationship of clinical presentation and calcification of culprit coronary artery stenoses. Arterioscler Thromb Vasc Biol. 2001;21:1618–1622.

    Article  PubMed  CAS  Google Scholar 

  71. 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.

    PubMed  CAS  Google Scholar 

  72. Mann J, Davies MJ. Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart. 1999;82:265–268.

    PubMed  CAS  Google Scholar 

  73. 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.

    Article  PubMed  CAS  Google Scholar 

  74. Haft JI, Haik BJ, Goldstein JE, Brodyn NE. Development of significant coronary artery lesions in areas of minimal disease. A common mechanism for coronary disease progression. Chest. 1988;94:731–736.

    Article  PubMed  CAS  Google Scholar 

  75. Bentzon JF, Sondergaard CS, Kassem M, Falk E. Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice. Circulation. 2007;116:2053–2061.

    Article  PubMed  CAS  Google Scholar 

  76. 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.

    Article  PubMed  CAS  Google Scholar 

  77. Falk E. Coronary thrombosis: pathogenesis and clinical manifestations. Am J Cardiol. 1991;68:28B–35B.

    Article  PubMed  CAS  Google Scholar 

  78. Falk E, Fernandez-Ortiz A. Role of thrombosis in atherosclerosis and its complications. Am J Cardiol. 1995;75:3B–11B.

    Article  PubMed  CAS  Google Scholar 

  79. Fernandez-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.

    Article  PubMed  CAS  Google Scholar 

  80. Leroyer AS, Isobe H, Leseche G, Castier Y, Wassef M, Mallat Z, Binder BR, Tedgui A, Boulanger CM. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol. 2007;49:772–777.

    Article  PubMed  CAS  Google Scholar 

  81. 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;57:329–335.

    Article  PubMed  Google Scholar 

  82. Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res. 2007;100:1673–1685.

    Article  PubMed  CAS  Google Scholar 

  83. 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

    Article  PubMed  Google Scholar 

  84. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Juhani Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W, Jr., Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation. 2003;108:1664–1672.

    Article  PubMed  Google Scholar 

  85. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W, Jr., Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation. 2003;108:1772–1778.

    Article  PubMed  Google Scholar 

  86. 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.

    Article  PubMed  Google Scholar 

  87. Waxman S, Ishibashi F, Muller JE. Detection and treatment of vulnerable plaques and vulnerable patients: novel approaches to prevention of coronary events. Circulation. 2006;114:2390–2411.

    Article  PubMed  Google Scholar 

  88. Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004;110:278–284.

    Article  PubMed  Google Scholar 

  89. 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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Atherosclerosis Research Unit, Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark

    Troels Thim

  2. Department of Zoophysiology, Institute of Biological Sciences, University of Aarhus, Aarhus, Denmark

    Mette Kallestrup Hagensen

  3. Department of Cardiology, Research Unit, Aarhus University Hospital, Aarhus, Denmark

    Jacob Fog Bentzon & Erling Falk

Authors
  1. Troels Thim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mette Kallestrup Hagensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacob Fog Bentzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erling Falk
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Endothelix, Inc., El Rio 8275, Houston, 77054, USA

    Morteza Naghavi

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Thim, T., Hagensen, M.K., Bentzon, J.F., Falk, E. (2011). Pathology of Vulnerability Caused by High-Risk (Vulnerable) Arteries and Plaques. In: Naghavi, M. (eds) Asymptomatic Atherosclerosis. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-179-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-179-0_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-178-3

  • Online ISBN: 978-1-60327-179-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation