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Plaque Rupture: Definition
Structural failure of the fibrocellular cap11
that
separates an atheromatous core22
from the lu...
Plaque Rupture: Definition
Plaque rupture ≠ Plaque disruption
Plaque rupture
Plaque erosion
Endothelial
disruption
Plaque Rupture: Definition
Plaque rupture ≠ Plaque disruption
Plaque rupture
Plaque erosion
Endothelial
disruption
Cardiovascular Risk Factors
athero-thrombosisathero-thrombosis
Traditional age and sex
cholesterol, LDL vs HDL
diabetes (m...
Plaque Rupture → Fatal Thrombosis
1460 coronary thrombi1460 coronary thrombi
Patients Age n Rupture Study
Hospital, ? ? 19...
Plaque Rupture → Fatal Thrombosis
EuropeEurope ≈≈ AsiaAsia ≈≈ USAUSA
Patients Age n Rupture Study
Hospital, AMI 62 y 88 71...
Plaque Rupture → Fatal Thrombosis
AsiaAsia:: JapanJapan ≈≈ ChinaChina
Patients Age n Rupture Study
Hospital, AMI 62 y 88 7...
Plaque Rupture → Fatal Thrombosis
hospitalhospital ≈≈ coroner/med.exam.coroner/med.exam.
Patients Age n Rupture Study
Hosp...
Plaque Rupture → Fatal Thrombosis
acute MIacute MI ≈≈ sudden deathsudden death
Patients Age n Rupture Study
Hospital, ? ? ...
Plaque Rupture → Fatal Thrombosis
age of deceasedage of deceased
Patients Age n Rupture Study
Hospital, ? ? 19 19 = 100% C...
Plaque Rupture → Fatal Thrombosis
sexsex
Sex n Rupture Study
p
Male 37 32 = 86% Falk-1983
134 113 = 84% Davies-1997
184 15...
Plaque Rupture → Fatal Thrombosis
sexsex && ageage
Sex Age, y n Rupture Study
Male >41, all 37 86% Falk-
1983
<50 7 86%
--...
Plaque Rupture → Fatal Thrombosis
sexsex && ageage
Sex Age, y n Rupture Study
Male >41, all 37 86% Falk-
1983
<50 7 86%
--...
Plaque Rupture → Coronary Thrombosis
burden of CHDburden of CHD
*MI + fatal CHD. AHA 2002 Heart and Stroke Statistical Upd...
Plaque Rupture → Coronary Thrombosis
burden of CHDburden of CHD
Annual heart attacks in the US: 1,107,000
Plaque erosionPl...
Plaque Rupture → Coronary Thrombosis
burden of CHDburden of CHD
Annual heart attacks in the US: 1,107,000
Plaque erosionPl...
Fatal Thrombosis: Rupture vs Non-rupture
ageage && sexsex
Rupture
+ - Study
p
Age, mean
53 y 44 y Farb-1996
<.02
68 y 70 y...
Fatal Thrombosis: Rupture vs Non-rupture
ageage && sexsex
Rupture
+ - Study
p
Age, mean
53 y 44 y Farb-1996
<.02
68 y 70 y...
Fatal Thrombosis: Rupture vs Non-rupture
whites vs blackswhites vs blacks
Rupture
+ - Study
p
Race
Race was not significan...
Fatal Thrombosis: Rupture vs Non-rupture
hypercholesterolemiahypercholesterolemia
Rupture
+ - Study
p
Cholesterol
Male
mg/...
Fatal Thrombosis: Rupture vs Non-rupture
hypertensionhypertension
Rupture
+ - Study
p
Hypertension
22% 11% Burke-1997
NS
3...
Fatal Thrombosis: Rupture vs Non-rupture
diabetes mellitus ~ type 2diabetes mellitus ~ type 2
Rupture
n + - Study
p
Diabet...
Fatal Thrombosis: Rupture vs Non-rupture
diabetes mellitus ~ type 2diabetes mellitus ~ type 2
Rupture
n + - Study
p
Diabet...
Fatal Thrombosis: Rupture vs Non-rupture
cigarette smokingcigarette smoking
Rupture
+ - Study
p
Smokers
71% 83% Burke-1997...
Fatal Thrombosis: Rupture vs Non-rupture
local flow and shearlocal flow and shear
Rupture
+ - Study
p
Stenosis, mean
area,...
Fatal Thrombosis: Rupture vs Non-rupture
plaque calcificationplaque calcification
Rupture
+ - Study
p
Calcification
69% 23...
Plaque Rupture → Fatal Thrombosis
exertion and sudden deathexertion and sudden death
Coronary thrombosis in men
n Rupture
...
Coronary Thrombosis: Virchow’s triad
pathogenesispathogenesis
Local Systemic = Blo
substrate flow coag.–plts.–fibr.lysis
q...
Coronary Thrombosis: Virchow’s triad
therapytherapy
Local Systemic = Blo
substrate flow coag.–plts.–fibr.lysis
queque
uptu...
Coronary Thrombosis: Virchow’s triad
therapytherapy
Local Systemic = Blo
substrate flow coag.–plts.–fibr.lysis
queque
uptu...
lipid-rich core
thrombus
cap
cap
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Plaque rupture definition

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Plaque rupture definition

  1. 1. Plaque Rupture: Definition Structural failure of the fibrocellular cap11 that separates an atheromatous core22 from the lumen of an atherosclerotic artery (ie, lumen ↔ core). 11 cap defect/gapcap defect/gap rupture, fissure, break, tear not just missing endotheliumnot just missing endothelium 22 lipid-richlipid-rich Greek athere, gruel (soft) Propensity to rupture  lipid-rich corelipid-rich core + → +++ no coreno core →→ no capno cap -
  2. 2. Plaque Rupture: Definition Plaque rupture ≠ Plaque disruption Plaque rupture Plaque erosion Endothelial disruption
  3. 3. Plaque Rupture: Definition Plaque rupture ≠ Plaque disruption Plaque rupture Plaque erosion Endothelial disruption
  4. 4. Cardiovascular Risk Factors athero-thrombosisathero-thrombosis Traditional age and sex cholesterol, LDL vs HDL diabetes (metabolic syndrome/exercise) smoking hypertension family history Novel inflammation: CRP, fibrinogen, IL, etc infection: Cp, CMV, HSV, Hp, ’burden’ homocysteine, folate, B6 coronary calcium: EBCT, IVUS carotid IMT
  5. 5. Plaque Rupture → Fatal Thrombosis 1460 coronary thrombi1460 coronary thrombi Patients Age n Rupture Study Hospital, ? ? 19 19 = 100% Chapman- 1965 Hospital, ? ? 17 17 = 100% Constantinides-1966 Hospital, AMI+SCD 58 y 40 39 = 98% Friedman-1966 Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius-1972 Coroner, SCD 53 y 20 19 = 95% Friedman-1973 Hospital, AMI 67 y 76 69 = 91% Horie-1978 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Coroner, SCD <65 y 32 26 = 81% Tracy-1985 Med.exam, SCD <70 y 61 39 = 64% El Fawal-1987 Hospital, AMI 83 52 = 63% Yutani-1987 Coroner, SCD? ? 85 71 = 84% Richardson-1989 Hospital, AMI 63 y 20 12 = 60% van der Wal-1994 Coroner, SCD (all?) ? 202 143 = 71% Davies-1997, update Hospital, AMI 69 y 291 218 = 75% Arbustini-1999 Hospital, AMI 61 y 61 56 = 92% Shi-1999 Hospital, AMI 69 y 100 81 = 81% Kojima-2000
  6. 6. Plaque Rupture → Fatal Thrombosis EuropeEurope ≈≈ AsiaAsia ≈≈ USAUSA Patients Age n Rupture Study Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius- 1972 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Med.exam, SCD <70 y 61 39 = 64% El Fawal- 1987 Coroner, SCD? ? 85 71 = 84% Richardson- 1989 Hospital, AMI 63 y 20 12 = 60% van der Wal- 1994 Coroner, SCD (all?) ? 202 143 = 71% Davies-1997, update Hospital, AMI 69 y 291 218 = 75% Arbustini- 1999 887 662 = 75% Europe Hospital, AMI 67 y 76 69 = 91% Horie-1978 Hospital, AMI 83 52 = 63% Yutani-1987 Hospital, AMI 61 y 61 56 = 92% Shi-1999 Hospital, AMI 69 y 100 81 = 81% Kojima-2000 320 258 = 81% Asia
  7. 7. Plaque Rupture → Fatal Thrombosis AsiaAsia:: JapanJapan ≈≈ ChinaChina Patients Age n Rupture Study Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius- 1972 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Med.exam, SCD <70 y 61 39 = 64% El Fawal- 1987 Coroner, SCD? ? 85 71 = 84% Richardson- 1989 Hospital, AMI 63 y 20 12 = 60% van der Wal- 1994 Coroner, SCD (all?) ? 202 143 = 71% Davies-1997, update Hospital, AMI 69 y 291 218 = 75% Arbustini- 1999 887 662 = 75% Europe Hospital, AMI 76 69 = 91% Horie- Japan Hospital, AMI 83 52 = 63% Yutani- Japan Hospital, AMI 61 56 = 92% Shi- China Hospital, AMI 100 81 = 81% Kojima-
  8. 8. Plaque Rupture → Fatal Thrombosis hospitalhospital ≈≈ coroner/med.exam.coroner/med.exam. Patients Age n Rupture Study Hospital, ? ? 19 19 = 100% Chapman- 1965 Hospital, ? ? 17 17 = 100% Constantinides-1966 Hospital, AMI+SCD 58 y 40 39 = 98% Friedman- 1966 Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius- 1972 Hospital, AMI 67 y 76 69 = 91% Horie-1978 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Hospital, AMI 83 52 = 63% Yutani-1987 Hospital, AMI 63 y 20 12 = 60% van der Wal- 1994 Hospital, AMI 69 y 291 218 = 75% Arbustini- 1999 Hospital, AMI 61 y 61 56 = 92% Shi-1999 Hospital, AMI 69 y 100 81 = 81% Kojima-2000 935 742 = 79% Hospital Coroner, SCD 53 y 20 19 = 95% Friedman- 1973 Coroner, SCD <65 y 32 26 = 81% Tracy-1985 Med.exam, SCD <70 y 61 39 = 64% El Fawal-
  9. 9. Plaque Rupture → Fatal Thrombosis acute MIacute MI ≈≈ sudden deathsudden death Patients Age n Rupture Study Hospital, ? ? 19 19 = 100% Chapman- 1965 Hospital, ? ? 17 17 = 100% Constantinides-1966 Hospital, AMI+SCD 58 y 40 39 = 98% Friedman- 1966 Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius- 1972 Hospital, AMI 67 y 76 69 = 91% Horie-1978 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Hospital, AMI 83 52 = 63% Yutani-1987 Hospital, AMI 63 y 20 12 = 60% van der Wal- 1994 Hospital, AMI 69 y 291 218 = 75% Arbustini- 1999 Hospital, AMI 61 y 61 56 = 92% Shi-1999 Hospital, AMI 69 y 100 81 = 81% Kojima-2000 935 742 = 79% Acute MI Coroner, SCD 53 y 20 19 = 95% Friedman- 1973 Coroner, SCD <65 y 32 26 = 81% Tracy-1985 Med.exam, SCD <70 y 61 39 = 64% El Fawal-
  10. 10. Plaque Rupture → Fatal Thrombosis age of deceasedage of deceased Patients Age n Rupture Study Hospital, ? ? 19 19 = 100% Chapman- 1965 Hospital, ? ? 17 17 = 100% Constantinides-1966 Hospital, AMI 83 52 = 63% Yutani-1987 Coroner, SCD? ? 85 71 = 84% Richardson- 1989 Coroner, SCD (all?) ? 202 143 = 71% Davies-1997, update 406 302 = 74% Age unknown Hospital, AMI 62 y 88 71 = 81% Bouch-1970 Hospital, AMI 66 y 91 68 = 75% Sinapius- 1972 Hospital, AMI 67 y 76 69 = 91% Horie-1978 Hospital, AMI 67 y 49 40 = 82% Falk-1983 Med.exam, SCD <70 y 61 39 = 64% El Fawal- 1987 Hospital, AMI 63 y 20 12 = 60% van der Wal- 1994 Hospital, AMI 69 y 291 218 = 75% Arbustini- 1999 Hospital, AMI 61 y 61 56 = 92% Shi-1999 Hospital, AMI 69 y 100 81 = 81% Kojima-2000 837 654 = 78% >60 years
  11. 11. Plaque Rupture → Fatal Thrombosis sexsex Sex n Rupture Study p Male 37 32 = 86% Falk-1983 134 113 = 84% Davies-1997 184 151 = 82% Arbustini- 1999 .0004 74 63 = 85% Kojima-2000 .08 → .4 94 64 = 68% Virmani- 2000, update 523 423 = 81% Female 12 8 = 67% Falk-1983 27 16 = 59% Davies-1997 107 67 = 63% Arbustini- 1999 26 18 = 69% Kojima-2000 31 10 = 32% Virmani- 2000, update
  12. 12. Plaque Rupture → Fatal Thrombosis sexsex && ageage Sex Age, y n Rupture Study Male >41, all 37 86% Falk- 1983 <50 7 86% ------------- +12 Females 50-70 22 82% ------------- >70 20 80% ------------- Male ~47 59 69% Burke-1997 unrelated to age
  13. 13. Plaque Rupture → Fatal Thrombosis sexsex && ageage Sex Age, y n Rupture Study Male >41, all 37 86% Falk- 1983 <50 7 86% ------------- +12 Females 50-70 22 82% ------------- >70 20 80% ------------- Male ~47 59 69% Burke-1997 unrelated to age
  14. 14. Plaque Rupture → Coronary Thrombosis burden of CHDburden of CHD *MI + fatal CHD. AHA 2002 Heart and Stroke Statistical Update. Annual heart attacks in the US: 1,107,000* • Men 668,000 Women, • ≥45 y 430,000 • <45 y 9,000 39% <1% 60%
  15. 15. Plaque Rupture → Coronary Thrombosis burden of CHDburden of CHD Annual heart attacks in the US: 1,107,000 Plaque erosionPlaque erosion is the major substrate for thrombosis in premenopausal women. Burke et al. Am Heart J 2001 39% 60% ~1%
  16. 16. Plaque Rupture → Coronary Thrombosis burden of CHDburden of CHD Annual heart attacks in the US: 1,107,000 Plaque erosionPlaque erosion is the major substrate for thrombosis in premenopausal women. Burke et al. Am Heart J 2001 Plaque rupturePlaque rupture is the major substrate in postmenopausal women and men ~1%
  17. 17. Fatal Thrombosis: Rupture vs Non-rupture ageage && sexsex Rupture + - Study p Age, mean 53 y 44 y Farb-1996 <.02 68 y 70 y Arbustini- 1999 NS 69 y 71 y Kojima-2000 NS Male 48 y 45 y Burke-1997 NS
  18. 18. Fatal Thrombosis: Rupture vs Non-rupture ageage && sexsex Rupture + - Study p Age, mean 53 y 44 y Farb-1996 <.02 68 y 70 y Arbustini- 1999 NS 69 y 71 y Kojima-2000 NS Male 48 y 45 y Burke-1997 NS
  19. 19. Fatal Thrombosis: Rupture vs Non-rupture whites vs blackswhites vs blacks Rupture + - Study p Race Race was not significantly (p>0.4) associated with plaque rupture in men* *Burke AP et al. N Engl J Med 1997;336:1276-82
  20. 20. Fatal Thrombosis: Rupture vs Non-rupture hypercholesterolemiahypercholesterolemia Rupture + - Study p Cholesterol Male mg/dlmg/dl 262 220 Burke-1997 .003 totaltotal::HDLHDL 8.5 5.0 Burke-1997 .003 Female mg/dlmg/dl 270 188 Burke-1998 .007 totaltotal::HDLHDL 6.2 6.0 Burke-1998 NS
  21. 21. Fatal Thrombosis: Rupture vs Non-rupture hypertensionhypertension Rupture + - Study p Hypertension 22% 11% Burke-1997 NS 38% 22% Burke-1998 NS 56% 58% Kojima-2000 NS
  22. 22. Fatal Thrombosis: Rupture vs Non-rupture diabetes mellitus ~ type 2diabetes mellitus ~ type 2 Rupture n + - Study p Diabetes 8 13% 33% Falk-1983 41 11% 64% Davies-1996, Circ 57 61% 42% Kojima-2000 NS GlycoHgb 59 7.9% 6.9% Burke-1997 NS
  23. 23. Fatal Thrombosis: Rupture vs Non-rupture diabetes mellitus ~ type 2diabetes mellitus ~ type 2 Rupture n + - Study p Diabetes 8 13% 33% Falk-1983 41 11% 64% Davies-1996, Circ 5757 61%61% 42%42% Kojima-2000Kojima-2000 NSNS GlycoHgb 5959 7.9%7.9% 6.9%6.9% Burke-1997Burke-1997 NSNS
  24. 24. Fatal Thrombosis: Rupture vs Non-rupture cigarette smokingcigarette smoking Rupture + - Study p Smokers 71% 83% Burke-1997 NS 50% 78% Burke-1998 NS 62% 26% Kojima-2000 .04
  25. 25. Fatal Thrombosis: Rupture vs Non-rupture local flow and shearlocal flow and shear Rupture + - Study p Stenosis, mean area, %area, % 91 93 Falk-1983 NS 78 70 Farb-1996 <.03 77 70 Burke-1998 NS 76 70 Kojima- 2000 NS diameter, %diameter, % 39 64 Davies-
  26. 26. Fatal Thrombosis: Rupture vs Non-rupture plaque calcificationplaque calcification Rupture + - Study p Calcification 69% 23% Farb-1996 .002
  27. 27. Plaque Rupture → Fatal Thrombosis exertion and sudden deathexertion and sudden death Coronary thrombosis in men n Rupture Study Acute exertion + 19 89% Burke* - 51 53% -------- *Burke et al. JAMA 1999;281:921-26
  28. 28. Coronary Thrombosis: Virchow’s triad pathogenesispathogenesis Local Systemic = Blo substrate flow coag.–plts.–fibr.lysis queque uptureupture +++ + on-ruptureon-rupture + +++ +++
  29. 29. Coronary Thrombosis: Virchow’s triad therapytherapy Local Systemic = Blo substrate flow coag.–plts.–fibr.lysis queque uptureupture +++ + on-ruptureon-rupture + +++ +++ Statins ASA, clopidogrel, warfarin, etc. ? ?
  30. 30. Coronary Thrombosis: Virchow’s triad therapytherapy Local Systemic = Blo substrate flow coag.–plts.–fibr.lysis queque uptureupture +++ + on-ruptureon-rupture + +++ +++ Statins ASA, clopidogrel, warfarin, etc. ? ? Additive?Additive?Additive?Additive?
  31. 31. lipid-rich core thrombus cap cap

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