plaque rupture definition

Plaque Rupture: Definition

Structural failure of the fibrocellular cap11 that separates an atheromatous core22 from the lumen of an atherosclerotic artery (ie, lumen core).1 1 cap defect/gapcap defect/gap rupture, fissure, break, tear

not just missing endotheliumnot just missing endothelium2 2 lipid-richlipid-rich Greek athere, gruel (soft)

Propensity to rupture lipid-rich corelipid-rich core + +++no core no core no cap no cap -

Plaque Rupture: Definition

Plaque rupture Plaque disruption

Plaque rupturePlaque erosionEndothelial

disruption

Cardiovascular Risk Factorsathero-thrombosisathero-thrombosis

Traditional age and sexcholesterol, LDL vs HDLdiabetes (metabolic syndrome/exercise)smokinghypertensionfamily history

Novel inflammation: CRP, fibrinogen, IL, etcinfection: Cp, CMV, HSV, Hp, ’burden’homocysteine, folate, B6

coronary calcium: EBCT, IVUScarotid IMT

Plaque Rupture Fatal Thrombosis1460 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 Med.exam, SCD 48 y 125 74 = 59% Virmani-2000, update

1460 1114 = 76%Worldwide

Plaque Rupture Fatal ThrombosisEurope Europe Asia Asia USA USA

Patients Age n Rupture StudyHospital, AMI 62 y 88 71 = 81% Bouch-1970Hospital, 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

Plaque Rupture Fatal ThrombosisAsiaAsia:: Japan Japan China China

Patients Age n Rupture StudyHospital, AMI 62 y 88 71 = 81% Bouch-1970Hospital, 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

Plaque Rupture Fatal Thrombosishospital hospital coroner/med.exam. coroner/med.exam.


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-1987Hospital, AMI 63 y 20 12 = 60% van der Wal-

1994Hospital, 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

Plaque Rupture Fatal Thrombosisacute MI acute MI sudden death sudden death


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-1987Hospital, AMI 63 y 20 12 = 60% van der Wal-

1994Hospital, 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

Plaque Rupture Fatal Thrombosisage of deceasedage of deceased


Hospital, ? ? 19 19 = 100% Chapman-1965 Hospital, ? ? 17 17 = 100%Constantinides-1966

Hospital, AMI 83 52 = 63% Yutani-1987Coroner, SCD? ? 85 71 = 84% Richardson-

1989Coroner, 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 yearsCoroner, SCD <65 y 32 26 = 81% Tracy-1985Hospital, AMI+SCD 58 y 40 39 = 98% Friedman-

1966Coroner, SCD 53 y 20 19 = 95% Friedman-

1973 Med.exam, SCD 48 y 125 74 = 59% Virmani-2000, update

217 158 = 73% <60 years

Plaque Rupture Fatal Thrombosissexsex

Sex n Rupture Studyp

Male 37 32 = 86% Falk-1983 134 113 = 84% Davies-1997 184 151 = 82% Arbustini-

1999 .000474 63 = 85% Kojima-2000

.08 .494 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%

Plaque Rupture Fatal Thrombosissex sex && age age

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

Female ~49, all 26 31%Burke-1998

<50 16 6%---------------

>50 10 70%---------------

Plaque Rupture Fatal Thrombosissex sex && age age

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

Female ~49, all 26 31%Burke-1998Burke-1998

<50<50 16 16 6% 6%---------------

>50>50 10 10 70%70%---------------

Plaque Rupture Coronary Thrombosisburden of CHDburden of CHD

*MI + fatal CHD. AHA 2002 Heart and Stroke Statistical Update.

Annual heart attacks in the US: 1,107,000*

• Men 668,000Women,• 45 y430,000• <45 y 9,000

39%

<1%60%


Annual heart attacks in the US: 1,107,000

Plaque erosionPlaque erosionis the major substratefor thrombosis inpremenopausal women.Burke et al. Am Heart J 2001

39%60%

~1%


Annual heart attacks in the US: 1,107,000

Plaque erosionPlaque erosionis the major substratefor thrombosis inpremenopausal women.Burke et al. Am Heart J 2001

Plaque rupturePlaque ruptureis the major substrate

in postmenopausal women and men

~1%

Fatal Thrombosis: Rupture vs Non-ruptureage age && sex sex

Rupture + - Study

p

Age, mean53 y 44 y Farb-1996

<.0268 y 70 y Arbustini-

1999 NS69 y 71 y Kojima-2000

NS

Male 48 y 45 y Burke-1997NS

Female 58 y 45 y Burke-1998.01

Fatal Thrombosis: Rupture vs Non-ruptureage age && sex sex

Rupture + - Study

p

Age, mean53 y 44 y Farb-1996

<.0268 y 70 y Arbustini-

1999 NS69 y 71 y Kojima-2000

NS

Male 48 y 45 y Burke-1997NS

FemaleFemale 58 y58 y 45 y45 y Burke-1998Burke-1998.01.01

Fatal Thrombosis: Rupture vs Non-rupturewhites 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

Fatal Thrombosis: Rupture vs Non-rupturehypercholesterolemiahypercholesterolemia

Rupture + - Study

p Cholesterol

Malemg/dlmg/dl 262 220 Burke-1997

.003totaltotal::HDLHDL 8.5 5.0 Burke-1997

.003Female

mg/dlmg/dl 270 188 Burke-1998.007

totaltotal::HDLHDL 6.2 6.0 Burke-1998NS

M+Fmmol/lmmol/l 5.5 5.1 Kojima-

2000 NScholchol 46% 50% Kojima-2000

NS

Fatal Thrombosis: Rupture vs Non-rupturehypertensionhypertension

Rupture + - Study

p

Hypertension22% 11% Burke-1997

NS38% 22% Burke-1998

NS56% 58% Kojima-2000

NS

Fatal Thrombosis: Rupture vs Non-rupturediabetes 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 26 8.8% 6.7% Burke-1998

NS

Fatal Thrombosis: Rupture vs Non-rupturediabetes 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 2626 8.8% 6.7%8.8% 6.7% Burke-1998Burke-1998

NSNS

Fatal Thrombosis: Rupture vs Non-rupturecigarette smokingcigarette smoking

Rupture + - Study

p

Smokers71% 83% Burke-1997

NS50% 78% Burke-1998

NS62% 26% Kojima-2000

.04

Fatal Thrombosis: Rupture vs Non-rupturelocal flow and shearlocal flow and shear

Rupture + - Study

p

Stenosis, mean

area, %area, % 91 93 Falk-1983NS

78 70 Farb-1996 <.03

77 70 Burke-1998NS

76 70 Kojima-2000 NS

diameter, %diameter, % 39 64 Davies-1996, Circ

Fatal Thrombosis: Rupture vs Non-ruptureplaque calcificationplaque calcification

Rupture + - Study

p

Calcification69% 23% Farb-1996

.002

Plaque Rupture Fatal Thrombosisexertion and sudden deathexertion and sudden death

Coronary thrombosis in men

n RuptureStudy

Acute exertion + 19 89%

Burke* - 51 53%

--------

*Burke et al. JAMA 1999;281:921-26

Coronary Thrombosis: Virchow’s triadpathogenesispathogenesis

Local Systemic = Blood substrate flow coag.–plts.–fibr.lysis

PlaquePlaque RuptureRupture +++ + + Non-ruptureNon-rupture + +++ +++

Coronary Thrombosis: Virchow’s triadtherapytherapy



Statins ASA, clopidogrel, warfarin, etc.? ?

Coronary Thrombosis: Virchow’s triadtherapytherapy



Statins ASA, clopidogrel, warfarin, etc.? ?

Additive?Additive?

lipid-rich corethrombus

cap

cap

plaque rupture definition

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