Plaque rupture definition

SHAPE Society

1. Plaque Rupture: Definition
Structural failure of the fibrocellular cap
11
that
separates an atheromatous core
22
from the lumen
of an atherosclerotic artery (ie, lumen « core).
1 1
cap defect/gapcap defect/gaprupture, fissure, break, tear
not just missing endotheliumnot just missing endothelium
2 2
lipid-richlipid-rich Greek athere, gruel (soft)
Propensity to rupture
 lipid-rich corelipid-rich core + ® +++
no core no core ®® no cap no cap -

2. Plaque Rupture: Definition
Plaque rupture ¹ Plaque disruption
Plaque rupture
Plaque erosion
Endothelial
disruption

3. Plaque Rupture: Definition
Plaque rupture ¹ Plaque disruption
Plaque rupture
Plaque erosion
Endothelial
disruption

4. Cardiovascular Risk Factors
athero-thrombosisathero-thrombosis
Traditionalage 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, B
6
coronary calcium: EBCT, IVUS
carotid IMT

5. Plaque Rupture ® Fatal Thrombosis
1460 coronary thrombi1460 coronary thrombi
Patients AgenRupture 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
Med.exam,SCD 48 y 125 74 =59% Virmani-2000,
update
1460 1114 = 76%
Worldwide

6. Plaque Rupture ® Fatal Thrombosis
Europe Europe »» Asia Asia »» USA USA
Patients AgenRupture 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
Hospital,? ? 19 19 = 100% Chapman-
1965
Hospital,? ? 17 17 = 100%
Constantinides-1966
Hospital,AMI+SCD 58 y 40 39 =98% Friedman-
1966
Coroner,SCD 53 y 20 19 =95% Friedman-
1973
Coroner,SCD <65 y 32 26 =81% Tracy-1985
Med.exam,SCD 48 y 125 74 =59% Virmani-
2000, update
253 194 = 77% USA

7. Plaque Rupture ® Fatal Thrombosis
AsiaAsia:: Japan Japan »» China China
Patients AgenRupture 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-
China
320 258 = 81% Asia
Hospital,? ? 19 19 = 100% Chapman-
1965
Hospital,? ? 17 17 = 100%
Constantinides-1966
Hospital,AMI+SCD 58 y 40 39 =98% Friedman-
1966
Coroner,SCD 53 y 20 19 =95% Friedman-
1973
Coroner,SCD <65 y 32 26 =81% Tracy-1985
Med.exam,SCD 48 y 125 74 =59% Virmani-
2000, update
253 194 = 77% USA

8. Plaque Rupture ® Fatal Thrombosis
hospital hospital »» coroner/med.exam. coroner/med.exam.
Patients AgenRupture 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-
1987
Coroner,SCD? ? 85 71 =84% Richardson-
1989
Coroner,SCD (all?) ? 202 143 = 71% Davies-1997,
update
Med.exam,SCD 48 y 125 74 =59% Virmani-
2000, update
525 372 = 71% Coroner

9. Plaque Rupture ® Fatal Thrombosis
acute MI acute MI »» sudden death sudden death
Patients AgenRupture 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-
1987
Coroner,SCD? ? 85 71 =84% Richardson-
1989
Coroner,SCD (all?) ? 202 143 = 71% Davies-1997,
update
Med.exam,SCD 48 y 125 74 =59% Virmani-
2000, update
525 372 = 71% Sudden
death

10. Plaque Rupture ® Fatal Thrombosis
age of deceasedage of deceased
Patients AgenRupture 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
Coroner,SCD <65 y 32 26 =81% Tracy-1985
Hospital,AMI+SCD 58 y 40 39 =98% Friedman-
1966
Coroner,SCD 53 y 20 19 =95% Friedman-
1973
Med.exam,SCD 48 y 125 74 =59% Virmani-
2000, update
217 158 = 73% <60 years

11. Plaque Rupture ® Fatal Thrombosis
sexsex
Sex nRupture 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
203 119 = 59%

12. Plaque Rupture ® Fatal Thrombosis
sex sex && age age
Sex Age, ynRupture 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
Female~49, all 26 31%
Burke-1998
<50 16 6%
---------------
>50 10 70%
---------------

13. Plaque Rupture ® Fatal Thrombosis
sex sex && age age
Sex Age, ynRupture 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
Female~49, all 26 31%
Burke-1998Burke-1998
<50<50 16 16 6% 6%
---------------
>50>50 10 10 70%70%
---------------

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,
•³45 y
430,000
•<45 y 9,000
39%
<1%
60%

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. 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. Fatal Thrombosis: Rupture vs Non-rupture
age age && sex sex
Rupture
+ - Study
p
Age, mean
53 y44 y Farb-1996
<.02
68 y70 y Arbustini-
1999NS
69 y71 y Kojima-2000
NS
Male 48 y45 y Burke-1997
NS
Female58 y45 y Burke-1998
.01

18. Fatal Thrombosis: Rupture vs Non-rupture
age age && sex sex
Rupture
+ - Study
p
Age, mean
53 y44 y Farb-1996
<.02
68 y70 y Arbustini-
1999NS
69 y71 y Kojima-2000
NS
Male 48 y45 y Burke-1997
NS
FemaleFemale58 y58 y45 y45 y Burke-1998Burke-1998
.01.01

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. 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 270188 Burke-1998
.007
totaltotal::HDLHDL 6.2 6.0 Burke-1998
NS
M+F
mmol/lmmol/l 5.5 5.1 Kojima-
2000NS
cholchol­­ 46%50% Kojima-2000
NS

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. Fatal Thrombosis: Rupture vs Non-rupture
diabetes mellitus ~ type 2diabetes mellitus ~ type 2
Rupture
n+ - Study
p
Diabetes
813%33% Falk-1983
4111%64% Davies-1996,
Circ
5761%42% Kojima-2000
NS
GlycoHgb
59 7.9% 6.9% Burke-1997
NS
268.8% 6.7% Burke-1998
NS

23. Fatal Thrombosis: Rupture vs Non-rupture
diabetes mellitus ~ type 2diabetes mellitus ~ type 2
Rupture
n+ - Study
p
Diabetes
813%33% Falk-1983
4111%64% Davies-1996,
Circ
575761%61%42%42% Kojima-2000Kojima-2000
NSNS
GlycoHgb
5959 7.9% 7.9% 6.9%6.9% Burke-1997Burke-1997
NSNS
26268.8% 6.7%8.8% 6.7% Burke-1998Burke-1998
NSNS

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. 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-
2000NS
diameter, %diameter, %39 64 Davies-
1996, Circ

26. Fatal Thrombosis: Rupture vs Non-rupture
plaque calcificationplaque calcification
Rupture
+ - Study
p
Calcification
69%23% Farb-1996
.002

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. Coronary Thrombosis: Virchow’s triad
pathogenesispathogenesis
Local Systemic = Blood
substrate flow coag.–plts.–fibr.lysis
PlaquePlaque
RuptureRupture +++ + +
Non-ruptureNon-rupture+ +++ +++

29. Coronary Thrombosis: Virchow’s triad
therapytherapy
Local Systemic = Blood
substrate flow coag.–plts.–fibr.lysis
PlaquePlaque
RuptureRupture +++ + +
Non-ruptureNon-rupture+ +++ +++
StatinsASA, clopidogrel, warfarin, etc.
? ?

30. Coronary Thrombosis: Virchow’s triad
therapytherapy
Local Systemic = Blood
substrate flow coag.–plts.–fibr.lysis
PlaquePlaque
RuptureRupture +++ + +
Non-ruptureNon-rupture+ +++ +++
StatinsASA, clopidogrel, warfarin, etc.
? ?
Additive?Additive?Additive?Additive?

31. lipid-rich core
thrombus
cap
cap