SHAPE Society

1. The “Evolution” of Coronary Atherosclerosis
(Libby. Circulation 2001;104: 365)
Normal
Artery
Lesion
Initiation
Fibro-fatty
Stage
Vulnerable
Plaque
Plaque
Rupture
Fibrous,
Calcified
Plaque
Endothelial
Erosion
Progression over time (yrs):

2. Can the Trajectories of the Natural Histories of
Coronary Atherosclerosis Be Identified
Prior to Adverse Coronary Events?
Opportunities for Intervention
Snapshot
at time of
angina or MI
Snapshot
to identify
vulnerability
Snapshot
to identify likelihood
to develop vulnerability
or progression
Quiescent,
Stable plaque
no symptoms
Fibrotic/
Scarred plaque
angina
Vulnerable,
Ruptured Plaque
MI, sudden death
?

3. The Effect of Physiologic Shear Stress on
Endothelial Structure and Function
Physiologic shear stress
(~15-50 dynes/cm2
) is
vasculoprotective:
(Malek, et al. JAMA 1999; 282:2035)
• Enhances endothelial quiescence
- decreases proliferation
• Enhances vasodilation
• Enhances anti-oxidant status
• Enhances anti-coagulant and
anti-thrombotic status

4. The Detrimental Effect of Low Shear Stress on
Endothelial Structure and Function
Low shear stresses and disturbed
local flow (< ~ 6 dynes/cm2
)
are atherogenic:
(Malek, et al. JAMA 1999; 282:2035)
• Cell proliferation, migration
• Expression of vascular adhesion
molecules, cytokines, mitogens
• Monocyte recruitment and activation
• Procoagulant and prothrombotic state
• Local oxidation
Promotes:

5. Original angiogram of
a portion of an artery
studied
Composite reconstruction of portion of the arterial
segment,
consisting of outer arterial wall, plaque, and lumen:
Isolated view of reconstructed outer arterial wall:
Isolated view of reconstructed lumen:
Isolated view of reconstructed atherosclerotic plaque:
Example of 3-D Reconstruction of Arterial Segment
(Stone, et al. Circulation 2003;108:438)

6. Coronary Endothelial Shear Stress
w
y
u
WSS
∂
∂
µ=
dynes/cm2
[Artery is displayed as if it were cut and opened longitudinally, as a
pathologist would view it.]
(Feldman and Stone. Curr Opin Cardiol 2000; 15: 430)

7. Changes
in Native
Arteries
Change in Plaque Thickness (mm) Change in EEM Radius (mm)
Change in Lumen Radius (mm) Change in ESS (dynes/cm2
)
Regions of baseline low ESS::
• increase in plaque thickness
• enlargement of EEM
(outward remodeling)
Regions of baseline
physiologic ESS:
• little change in any variable
Regions of baseline
increased ESS:
• increase in lumen radius
• increase in EEM radius
• decrease in ESS
(outward remodeling)
ESS at Baseline and
Vascular Outcomes 6 mo later:
p<0.001
p<0.001p=0.03
(Stone, et al. Circulation 2003;108:438)

8. Prediction of Areas of Minor Obstruction
Which Are Actively Progressing
Identification of Limits of Outward Remodeling and
Initiation of Lumen Narrowing In-vivo
(Feldman, et al 2003, submitted)
(Confirmation of Glagov Hypothesis)

9. New Era of “Preventive” Vascular Approaches:
Identification of High-Risk, Minor Obstructions and Application of
Focused Interventions
To Avert Adverse Coronary Events
Lesion
at time of
clinical event
Identification
of “vulnerability”
Minor lesion likely to
become vulnerable
or progress
Quiescent,
Stable plaque
no symptoms
Fibrotic/
Scarred plaque
angina
Vulnerable,
Ruptured Plaque
MI, sudden death
X X
X

10. New Era of “Preventive” Vascular Approaches:
Identification of High-Risk, Minor Obstructions and Application of
Focused Interventions
To Avert Adverse Coronary Events
Lesion
at time of
clinical event
Identification
of “vulnerability”
Minor lesion likely to
become vulnerable
or progress
Quiescent,
Stable plaque
no symptoms
Fibrotic/
Scarred plaque
angina
Vulnerable,
Ruptured Plaque
MI, sudden death
X X
X