progression, regression, and remodeling of atherosclerosis ( 동맥경화증의 진행, 퇴축,...

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.