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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
The Spectrum of Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
Clinical Conditions involving Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
Longitudinal & Cross Sectional Images (Positive Remodeling)
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Extremes of Vascular RemodelingRR = EEM area lesion / EEM area prox reference
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Tomographic Sections of Human Coronary Artery(IVUS image)
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Tomographic Sections of
Human Coronary Artery(IVUS image)
Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.
Negative Remodeling(RR = 11.5/16.0 = 0.71)
Positive Remodeling(RR = 18.9/14.9 = 1.32)
Various Types of Vascular Remodeling
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
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
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
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
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
Birnbaum Y,, Siegel RJ. JACC 1997;30;1149-64.
Two Extremes of Vascular Remodeling
Nishioka T,, Siegel RJ. JACC 1996;27;1571-6.
(+)
(-)
Proportions of Positive or Negative Remodeling(IVUS Data of Human Coronary Primary Atherosclerosis)
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#
Siegel RJ, et al. [letter] Circulation 1996;94;3005-6.
Saphenous Vein Graft Atherosclerosis at the Site of Venous Valves
Nishioka T,, Siegel RJ. Circulation 1996;93;683-90.
Absence of Positive Remodeling in Saphenous Vein Bypass Graft ( IVUS Data )
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Direction of Remodeling & Plaque Stability
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
Nissen SE & Yock P. Circulation 2001;103;604-616.
Ruptured Plaque with Positive Remodeling• Prox Reference • Ruptured Plaque
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 ?
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
Mechanism of Negative Remodeling
Early 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
Serial Observation of Arterial Remodeling
Schoenhagen P,, Nissen SE, Tuzcu EM. JACC 2001;38;297-306.
Luo H,, Siegel RJ. ATVB 1996;16;1393-8.
Association of Remodeling & Restenosis after Coronary Balloon Angioplasty
Restenotic
Patent
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
Mechanism of Negative Remodeling after PTCA or DCA
Adventitial 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
The Agents of Vascular Remodeling
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
The Factors that modulate the Growth of VSMC
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
Mediators of Vascular Remodeling in ECM
Gibbons G & Dzau VJ NEJM 1994;330;1431-8
Progression, Regression, and Remodeling
Glagov S, et al. NEJM 1987;316;1371-53.
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.
