The Evolution of Coronary Atherosclerosis

1
The Evolution of Coronary Atherosclerosis
Progression over time (yrs)
Normal Artery
Lesion Initiation
Fibro-fatty Stage
Vulnerable Plaque
Plaque Rupture
Fibrous, Calcified Plaque
Endothelial Erosion
(Libby. Circulation 2001104 365)
2
Can the Trajectories of the Natural Histories of
Coronary Atherosclerosis Be IdentifiedPrior to
Adverse Coronary Events?Opportunities for
Intervention
Quiescent, Stable plaque no symptoms
Fibrotic/ Scarred plaque angina
?
Vulnerable, Ruptured Plaque MI, sudden death
Snapshot to identify likelihood to develop
vulnerability or progression
Snapshot at time of angina or MI
Snapshot to identify vulnerability
3
The Effect of Physiologic Shear Stress on
Endothelial Structure and Function
Physiologic shear stress (15-50 dynes/cm2)
is vasculoprotective

• Enhances endothelial quiescence
• - decreases proliferation

• Enhances vasodilation

• Enhances anti-oxidant status

• Enhances anti-coagulant and
• anti-thrombotic status

(Malek, et al. JAMA 1999 2822035)
4
The Detrimental Effect of Low Shear Stress on
Endothelial Structure and Function
Low shear stresses and disturbed local flow (lt
6 dynes/cm2) are atherogenic
Promotes

• Cell proliferation, migration

• Expression of vascular adhesion molecules,
  cytokines, mitogens

• Monocyte recruitment and activation

• Procoagulant and prothrombotic state

• Local oxidation

(Malek, et al. JAMA 1999 2822035)
5
Example of 3-D Reconstruction of Arterial Segment
Composite reconstruction of portion of the
arterial segment, consisting of outer arterial
wall, plaque, and lumen
Original angiogram of a portion of an
artery studied
Isolated view of reconstructed outer arterial
wall
Isolated view of reconstructed lumen
Isolated view of reconstructed atherosclerotic
plaque
(Stone, et al. Circulation 2003108438)
6
Coronary Endothelial Shear Stress
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
plt0.001
ESS at Baseline and Vascular Outcomes 6 mo later
Regions of baseline low ESS increase in plaque
thickness enlargement of EEM (outward
remodeling)
plt0.001
p0.03
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)
(Stone, et al. Circulation 2003108438)
8
Prediction of Areas of Minor ObstructionWhich
Are Actively ProgressingIdentification of Limits
of Outward Remodeling and Initiation of Lumen
Narrowing In-vivo
(Confirmation of Glagov Hypothesis)
(Feldman, et al 2003, submitted)
9
New Era of Preventive Vascular Approaches
Identification of High-Risk, Minor Obstructions
and Application of Focused InterventionsTo Avert
Adverse Coronary Events
Quiescent, Stable plaque no symptoms
Fibrotic/ Scarred plaque angina
X
X
X
Vulnerable, Ruptured Plaque MI, sudden death
Lesion at time of clinical event
Identification of vulnerability
Minor lesion likely to become vulnerable or
progress