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Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행 , 퇴축 , ...
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Transcript of Progression, Regression, and Remodeling of Atherosclerosis ( 동맥경화증의 진행 , 퇴축 , ...
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Progression, Regression, and Remodeling
of Atherosclerosis
( 동맥경화증의 진행 , 퇴축 , 그리고 재성형 )
Hyo-Soo Kim, MD, PhD
Cardiovascular Center,
Seoul National University Hospital, Seoul, Korea
김 효 수
서울대학교병원 심혈관센터
서울대학교 의과대학 내과학교실
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The Spectrum of Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
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Clinical Conditions involving Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
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Longitudinal & Cross Sectional Images (Positive Remodeling)
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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Extremes of Vascular RemodelingRR = EEM area lesion / EEM area prox reference
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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Tomographic Sections of Human Coronary Artery(IVUS image)
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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Tomographic Sections of
Human Coronary Artery(IVUS image)
Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.
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Negative Remodeling(RR = 11.5/16.0 = 0.71)
Positive Remodeling(RR = 18.9/14.9 = 1.32)
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Various Types of Vascular Remodeling
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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Nissen SE & Yock P. Circulation 2001;103;604-616.
Positive Remodeling at Early Stage of Atherosclerosis Results in False Negative on CAG
• Distal Reference
• Positive Remodeling at Early Lesion
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Nissen SE & Yock P. Circulation 2001;103;604-616.
Negative Remodeling in addition to Neointimal FormationResults in Significant Stenosis on CAG
• Distal Reference • Stenotic Lesion
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The Possible Sequential Changes of Atherosclerotic Artery( based on the postmortem analysis of 136 LMCA )
Glagov S, et al. NEJM 1987;316;1371-53.
Early Phase : OvercompensationVss Enlargement > Plaque Accumulation
Late Phase : DecompensationVss Enlargement < Plaque Accumulation
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Segmental Comparison between
Normal and Atherosclerotic Human Coronary Artery
Zarins CK,, Glagov S. J Vasc Surg 1988;7;386.
Pts = 125LAD = 481 segsLAD with Atherosclerosis : Plaq Area correlates with Vss Area : compensatory enlargement : esp, at distal segment
LAD in best quartile LAD in worst quartile
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Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.
Two Extremes of Vascular Remodeling
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Nishioka T,, Siegel RJ. JACC 1996;27;1571-6.
(+)
(-)
Proportions of Positive or Negative Remodeling(IVUS Data of Human Coronary Primary Atherosclerosis)
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Nishioka T,, Siegel RJ. JACC 1996;27;1571-6. # Mintz GS, et al. Circulation 1997;95;1791 Lim TT, et al. Circulation 1997;95;855-9.
Proportions of Positive or Negative Remodeling(IVUS Data of Human Coronary Primary Atherosclerosis)
55% 20% 25% 15% or 22% in other studies#
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Siegel RJ, et al. [letter] Circulation 1996;94;3005-6.
Saphenous Vein Graft Atherosclerosis at the Site of Venous Valves
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Nishioka T,, Siegel RJ. Circulation 1996;93;683-90.
Absence of Positive Remodeling in Saphenous Vein Bypass Graft ( IVUS Data )
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Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Direction of Remodeling & Plaque Stability
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Nissen SE & Yock P. Circulation 2001;103;604-616.
Direction of Remodeling & Plaque Stability
•Early Phase of Atherosclerosis•Compensatory Enlargement •Positive Remodeling•Unstable Plaque
•Late Phase of Atherosclerosis•Shrinkage of Vessel•Negative Remodeling•Stable Plaque
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Nissen SE & Yock P. Circulation 2001;103;604-616.
Ruptured Plaque with Positive Remodeling• Prox Reference • Ruptured Plaque
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Summary of Vascular Remodeling in Native Coronary Atherosclerosis
1. Sequential Change of Remodeling (in Histologic study)
• Compensatory enlargement at early phase
• No lumen loss until plaque area reaches 40% of EEM area
2. Proportion of Remodeling (in IVUS study)
• 50% of lesions show compensatory enlargement
• 15 ~ 25 % of lesions show vascular shrinkage
• Shrinkage is highly associated with lesion calcification
3. Special Issues on Compensatory Enlargement
• impaired in DM & smokers & saphenous vein graft
• greater in eccentric lesion or concentric lesion ?
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Mechanism of Positive Remodeling in Early Atherosclerosis
Medial change
Atherosclerosis
Atrophy & thinning of media
weakening of the arterial wall
dilatation
Shear stress change
Expanding atheroma
lumen narrowing
increased shear stress
dilatation with normalization of shear stress
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Mechanism of Negative RemodelingEarly event ? (failure of the adaptive compensatory dilation)
• Calcified lesion is highly associated with negative remodeling
• Fibrocalcific element limits adaptive positive remodeling ?
Late event ? (active arterial shrinkage)
• Mature plaque
with increased fibrous and calcific deposits & apoptosis
as well as decreased lipid content
results in retraction
Contributing factor ? (Venturi effect)
• Vascular narrowing rapid flow & low pressure shrinkage
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Serial Observation of Arterial Remodeling
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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Luo H,, Siegel RJ. ATVB 1996;16;1393-8.
Association of Remodeling & Restenosis after Coronary Balloon Angioplasty
Restenotic
Patent
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Summary of Vascular Remodeling during Restenosis after PTCA or DCA
1. Vascular shrinkage is important determinant for restenosis
• 75% of luminal loss d/t decrease of EEM area
• 25% of luminal loss d/t increase of Plaque area
2. Shrinkage is more important
• for restenosis after balloon or DCA with shallow injury
3. Intimal hyperplasia is more important
• for restenosis after DCA with deep injury or stenting
• DM pts
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Mechanism of Negative Remodeling after PTCA or DCAAdventitial role
Overstretch & deep tear
Inflammation & proliferation
& differentiation of Fb to myofibroblast
Contraction of adventitial scar
Late lumen narrowing
Determinant of Remodeling Direction ?
• Severity and depth of the wall injury
• Extent of inflammatory reaction
• Pressure, wall stress, & flow through lesion
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The Agents of Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
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The Factors that modulate the Growth of VSMC
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
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Mediators of Vascular Remodeling in ECM
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
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Progression, Regression, and Remodeling
Glagov S, et al. NEJM 1987;316;1371-53.
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Atherosclerosis Regression Trial with IVUS F/Uby Lipid-Lowering Agent
REVERSAL (Reversal of Atherosclerosis with Lipitor)
Nissen SE. AJC 2000;86(suppl 1);12-17H.