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Plaque Rupture Definition
Structural failure of the fibrocellular cap1 that
separates an atheromatous core2 from the lumen of
an atherosclerotic artery (ie, lumen ? core). 1
cap defect/gap rupture, fissure, break,
tear not just missing
endothelium 2 lipid-rich Greek athere,
gruel (soft) Propensity to
rupture ? lipid-rich core ? no
core ? no cap -
2
Plaque Rupture Definition
Plaque rupture ? Plaque disruption
Plaque rupture P
laque erosion Endothelial
disruption
3
Plaque Rupture Definition
Plaque rupture ? Plaque disruption
Plaque rupture P
laque erosion Endothelial
disruption
4
Cardiovascular Risk Factors athero-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
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Plaque Rupture ? Fatal Thrombosis 1460 coronary
thrombi
Patients Age n Rupture Study
Hospital, ? ? 19 19
100 Chapman-1965 Hospital, ?
? 17 17 100 Constantinides-1966
Hospital, AMISCD 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
lt65 y 32 26 81 Tracy-1985
Med.exam, SCD lt70 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
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Plaque Rupture ? Fatal Thrombosis Europe ? Asia ?
USA
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 lt70
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-199
9 887 662
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, AMISCD
58 y 40 39 98 Friedman-1966
Coroner, SCD 53 y 20 19
95 Friedman-1973 Coroner, SCD
lt65 y 32 26 81 Tracy-1985
Med.exam, SCD 48 y 125 74
59 Virmani-2000, update
253 194 77 USA
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Plaque Rupture ? Fatal Thrombosis Asia Japan ?
China
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 lt70
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-199
9 887 662
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, AMISCD
58 y 40 39 98 Friedman-1966
Coroner, SCD 53 y 20 19
95 Friedman-1973 Coroner, SCD
lt65 y 32 26 81 Tracy-1985
Med.exam, SCD 48 y 125 74
59 Virmani-2000, update
253 194 77 USA
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Plaque Rupture ? Fatal Thrombosis hospital ?
coroner/med.exam.
Patients Age n Rupture Study
Hospital, ? ? 19 19
100 Chapman-1965 Hospital, ?
? 17 17 100 Constantinides-1966
Hospital, AMISCD 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 6
3 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 Cor
oner, SCD lt65 y 32 26
81 Tracy-1985 Med.exam, SCD lt70
y 61 39 64 El Fawal-1987 Coroner, S
CD? ? 85 71 84 Richardson-19
89 Coroner, SCD (all?) ? 202
143 71 Davies-1997, update
Med.exam, SCD 48 y 125 74
59 Virmani-2000, update
525 372 71 Coroner
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Plaque Rupture ? Fatal Thrombosis acute MI ?
sudden death
Patients Age n Rupture Study
Hospital, ? ? 19 19
100 Chapman-1965 Hospital, ?
? 17 17 100 Constantinides-1966
Hospital, AMISCD 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 6
3 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 Coro
ner, SCD lt65 y 32 26
81 Tracy-1985 Med.exam, SCD lt70
y 61 39 64 El Fawal-1987 Coroner, S
CD? ? 85 71 84 Richardson-19
89 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
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Plaque Rupture ? Fatal Thrombosis age of deceased
Patients Age n Rupture Study
Hospital, ? ? 19 19
100 Chapman-1965 Hospital, ?
? 17 17 100 Constantinides-1966 Ho
spital, 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 lt70
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 gt60 years Coroner, SCD
lt65 y 32 26 81 Tracy-1985 Hospita
l, AMISCD 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 lt60 years
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Plaque Rupture ? Fatal Thrombosis
sex
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 203 119
59
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Plaque Rupture ? Fatal Thrombosis
sex age
Sex Age, y n Rupture Study
Male gt41, all 37 86 Falk-1983
lt50 7 86 -------------
12 Females 50-70 22 82 -----------
-- gt70 20 80 ------------
- Male 47 59 69 Burke-1997
unrelated to age
Female 49, all 26 31 Burke-1998
lt50 16 6 ---------------
gt50 10 70 ---------------
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Plaque Rupture ? Fatal Thrombosis
sex age
Sex Age, y n Rupture Study
Male gt41, all 37 86 Falk-1983
lt50 7 86 -------------
12 Females 50-70 22 82 -----------
-- gt70 20 80 ------------
- Male 47 59 69 Burke-1997
unrelated to age
Female 49, all 26 31 Burke-1998
lt50 16 6 ---------------
gt50 10 70 ---------------
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Plaque Rupture ? Coronary Thrombosis burden of CHD
Annual heart attacks in the US 1,107,000

• Men 668,000
• Women,
• ?45 y 430,000
• lt45 y 9,000

39
60
lt1
MI fatal CHD. AHA 2002 Heart and Stroke
Statistical Update.
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Plaque Rupture ? Coronary Thrombosis burden of CHD
Annual heart attacks in the US 1,107,000
39
60
Plaque erosion is the major substrate for
thrombosis in premenopausal women. Burke et al.
Am Heart J 2001
1
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Plaque Rupture ? Coronary Thrombosis burden of CHD
Annual heart attacks in the US 1,107,000
Plaque rupture is the major substrate in
postmenopausal women and men
Plaque erosion is the major substrate for
thrombosis in premenopausal women. Burke et al.
Am Heart J 2001
1
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Fatal Thrombosis Rupture vs Non-rupture age sex
Rupture -
Study p Age, mean 53
y 44 y Farb-1996 lt.02 68
y 70 y Arbustini-1999 NS 69
y 71 y Kojima-2000 NS Male 48
y 45 y Burke-1997 NS Female 58
y 45 y Burke-1998 .01
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Fatal Thrombosis Rupture vs Non-rupture age sex
Rupture -
Study p Age, mean 53
y 44 y Farb-1996 lt.02 68
y 70 y Arbustini-1999 NS 69
y 71 y Kojima-2000 NS Male 48
y 45 y Burke-1997 NS Female 58
y 45 y Burke-1998 .01
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Fatal Thrombosis Rupture vs Non-rupture whites
vs blacks
Rupture -
Study p Race Race was
not significantly (pgt0.4) associated
with plaque rupture in men Burke AP et al.
N Engl J Med 19973361276-82
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Fatal Thrombosis Rupture vs Non-rupture hyperchol
esterolemia
Rupture -
Study p Cholesterol Male mg/dl
262 220 Burke-1997 .003 tota
lHDL 8.5 5.0 Burke-1997 .003 F
emale mg/dl 270 188 Burke-1998
.007 totalHDL 6.2 6.0 Burke-1998
NS MF mmol/l 5.5
5.1 Kojima-2000 NS chol? 46 50
Kojima-2000 NS
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Fatal Thrombosis Rupture vs Non-rupture hypertens
ion
Rupture -
Study p Hypertension
22 11 Burke-1997 NS 38
22 Burke-1998 NS 56 58
Kojima-2000 NS
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Fatal Thrombosis Rupture vs Non-rupture diabetes
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 26 8.8
6.7 Burke-1998 NS
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Fatal Thrombosis Rupture vs Non-rupture diabetes
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 26 8.8
6.7 Burke-1998 NS
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Fatal Thrombosis Rupture vs Non-rupture cigarette
smoking
Rupture -
Study p Smokers 71
83 Burke-1997 NS 50 78
Burke-1998 NS 62 26 K
ojima-2000 .04
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Fatal Thrombosis Rupture vs Non-rupture local
flow and shear
Rupture -
Study p Stenosis, mean area,
91 93 Falk-1983 NS
78 70 Farb-1996
lt.03 77 70 Burke-1998 N
S 76 70 Kojima-2000 NS
diameter, 39 64 Davies-1996, Circ
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Fatal Thrombosis Rupture vs Non-rupture plaque
calcification
Rupture -
Study p Calcification
69 23 Farb-1996 .002
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Plaque Rupture ? Fatal Thrombosis exertion and
sudden death
Coronary thrombosis in men n R
upture Study Acute exertion
19 89 Burke -
51 53 --------
Burke et al. JAMA 1999281921-26
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Coronary Thrombosis Virchows triad pathogenesis
Local Systemic Blood
substrate flow coag.plts.fibr
.lysis Plaque Rupture
Non-rupture

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Coronary Thrombosis Virchows triad therapy
Local Systemic Blood
substrate flow coag.plts.fibr
.lysis Plaque Rupture
Non-rupture

?
?
Statins
ASA, clopidogrel, warfarin, etc.
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Coronary Thrombosis Virchows triad therapy
Local Systemic Blood
substrate flow coag.plts.fibr
.lysis Plaque Rupture
Non-rupture

?
?
Statins
ASA, clopidogrel, warfarin, etc.
Additive?
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cap
lipid-rich core
thrombus
cap