Review

VULNERABLE PLAQUES

SOHAIB AHMAD;NADIA SHIRAZI; M.U. RABBANI

HOW TO DEFINE A VULNERABLE PLAQUE?

The term, vulnerable plaque, has been used synonymously with the
terms high-risk plaque, thrombosis-prone plaque, thin-cap fibroatheromas
(TCFAs), unstable plaque and disrupted plaque and refers to a plaque at
increased risk of causing thrombosis and lesion progression [1].
Plaque rupture was first recognized as the initiating event of most
cardiovascular diseases in 1966 and has been under extensive study ever since
[2]
.
Prospectively, a vulnerable plaque can be defined as a plaque
identified by the technology tested and documented to have a high likelihood
of forming a thrombogenic focus. The thrombus could thus produce
immediate disease onset, or rapid, asymptomatic, angiographic progression.
On the other hand, a plaque with a low likelihood of causing such an outcome
would be termed non-vulnerable [1].
The American Heart Association (AHA) classifies plaques into six
types based on histologic features – Type I (initial changes); type II (fatty
streak); type III (pre-atheroma); type IV (atheroma); type V (fibroatheroma);
and type VI (complicated plaque) – all thrombosed lesions are included in
type VI as complicated lesions [3,4].
CHARACTERISTICS OF A VULNERABLE PLAQUE
Although evidence suggests that certain features can identify
vulnerable plaques but no conclusive data exists. The following features in a
plaque have been implicated as being predictive of an adverse outcome: [5,6]
A] Large lipid core (40% of the entire plaque)
B] Thin cap
C] Increased macrophage content
D] Increased proteoglycan content
E] Presence of a calcified nodule
There are no prospective studies clearly establishing any particular
Authors’ affiliations: histologic type as being vulnerable plaque; also it is not possible to identify
Sohaib Ahmad the frequency of vulnerable plaque due to unavailability of a simple method of
Prof. M.U.Rabbani identifying such plaques. Autopsy based studies have a certain selection bias,
Centre of Cordiology but the best evidence about the frequency of various histologic types of
NADIA SHIRAZI plaques comes from postmortem studies [1].
Department of Pathology Three major factors determine the vulnerability of the fibrous cap: [7]
JN Medical College A] Circumferential wall stress or cap fatigue
Aligarh Muslim University, ALIGARH
B] Lesion characteristics- location, size and consistency
C] Blood flow characteristics
Platelet disruption involves inflammation as an important adjunct to
mechanical factors [8] and activated inflammatory cells have been detected in
the disrupted areas of atherectomy specimens from patients with acute
ADDRESS FOR CORRESPONDENCE coronary syndromes. These inflammatory cells secrete proteolytic enzymes
DR. SOHAIB AHMAD such as matrix metalloproteinases and are capable of degrading the
2-Basera,Dodhpur, Opposite extracellular matrix, affect vascular remodeling and migration of smooth
Bombay Merchantile Bank, muscle cells across the basement membrane [9].
Aligarh (UP)-202002, INDIA Lesion thrombogenicity has also been linked with tissue factor
E-mail: sohadia@hotmail.com content and local tissue factor inhibition reduces lesion thrombogenicity [10].
Phone No. 0091-571-2702284/ 0091- Evidence also suggests that increased tissue factor expression is associated
9412460098/ 0091-9837172466 with cell apoptosis [11].
LESIONS THAT LEAD TO ACUTE CORONARY SYNDROMES
Atleast 65-70% of the atherothrombi are caused by plaque rupture,
25-30% of thrombi occur from plaque erosion and 2-5% of atherothrombi
JK- Practitioner 2006; 13 (1):1-4 occur as a result of calcified nodules that protrude into the lumen.
1] Plaque Rupture
Keywords: vulnerable plaque, Intravascular ultrasound, Thin-cap Fibroatheroma

JK- Practitioner Vol.13, No. 1, January - March 2006 1

Review
Plaque rupture is defined as a necrotic core with
a thin fibrous cap that is disrupted or ruptured, allowing
the flowing blood to come in contact with the necrotic
core. Rupture of the fibrous cap usually occurs in the
shoulder regions, the weakest portion where the stress is
highest and matrix metalloproteinase production is
increased [12].
The frequency of plaque rupture reported in
various series of sudden coronary deaths varies from 30%
[13]
to over 85% [14, 15]. Calcification is present in 80% of
plaques that rupture but is usually either speckled or
fragmented and infrequently diffuse. The coronary
plaques in plaque rupture are equally concentric or
eccentric and are more frequent in men and
postmenopausal women [16].
2] Plaque Erosion
It is defined as a lesion with luminal thrombus
with a base rich in smooth muscle cells and proteoglycan
matrix [17]. At the site of thrombosis, there is absence of an
endothelial layer. These lesions are usually not calcified,
or have speckled calcification if calcified [18]. Majority of
plaque erosions are eccentric and occur most frequently in
young men and women less than 50 years of age and are
associated with smoking especially in premenopausal
women [19].
3] Calcified Nodule
An infrequent cause of thrombosis in patients
dying a sudden cardiac death, it refers to a lesion with a
fibrous cap disruption, absence of endothelium and
thrombus associated, dense calcified nodule with bone
formation. The origin of calcified nodule is thought to be
associated with healed plaque ruptures. Mid-right
coronary artery accounts for over 50% of the cases
because of maximum torsion stress and is the lesion is
usually seen in elderly males with heavily calcified and
tortuous arteries [20].
4] Thin-cap Fibroatheroma
The thin-cap fibroatheroma (TCFA) has been
defined as a lesion with a fibrous cap < 65µm thick and
infiltrated by macrophages (>25 cells per 0.3 mm
diameter field) [21]. The cap may or may not be eccentric
and the necrotic core is well developed. Over 50% of the
plaque ruptures, healed plaque ruptures and TCFAs occur
in the proximal portions of the major coronary arteries
with < 50% diameter stenosis and another third in the mid-
portion of these arteries while the rest are distributed in the
distal segments [22]. Fifty percent of TCFAs have absent or
speckled calcification, and the remainder has a diffuse or a
fragmented calcification pattern [18].
DIAGNOSIS OF THE VULNERABLE PLAQUE
Since the consequences of rupture of vulnerable
plaque may be catastrophic, their identification is of
paramount significance to enable the development of
treatment modalities to stabilize such plaques.
a)Coronary Angiography: It is the gold standard
for assessment of obstructive
lesions but it fails to assess the
plaque burden. Also, since 70% of
acute coronary occlusions are in
areas that were angiographically
2 JK- Practitioner Vol.13, No. 1, January - March 2006
normal previously, the technique is
severely limited in identifying
vulnerable plaque. [23]
b)Angioscopy: More sensitive than angiography, it
offers direct visualization of the plaque
surface and intraluminal structures like
tears and color of the thrombi. .
However, angioscopy is difficult to
perform, is invasive, is associated with
a risk of peri-procedural ischaemia and
only a limited part of the vessel tree can
be investigated. [24]
c) IntravascularUltrasound (IVUS): Provides real
time high-resolution images of the
vessel wall and lumen. Only structures
over 160 µ m can be visualized
a c c u r a t e l y. C a l c i f i c a t i o n i s
characterized by a bright echo signal
with distal shadows that hide plaque
components and deeper vessel
structures. The sensitivity of detection
of micro-calcification is around 60% [25].
Lipid deposition is described as
echoluscent zones and can be detected
on IVUS with a sensitivity of between
78 and 95% and specificity of 30% [26].
The sensitivity to differentiate between
fatty and fibrous tissue is between 39
and 52% [27]. IVUS assessment of
vascular remodeling may help to
classify plaques with the highest
[28]
probability of spontaneous rupture .
d)Intravascular Elastography: Based on the
concept that upon uniform loading, the
local relative amount of deformation of
a tissue is related to the local
mechanical properties of that tissue,
this technique differentiates between
hard and soft tissue that may be
important for detection of a deformable
plaque prone to rupture.
e) Other Techniques:
l Optical Coherence Tomography
l Thermography
l Raman Spectroscopy
l Near-Infrared Spectroscopy
l Magnetic Resonance Imaging
l Shear Stress Imaging
All the techniques are still under development and at
present none of them can identify a vulnerable plaque alone or
predict its further development. Thus a combination of
various modalities will be important in the future to ensure
high sensitivity and specificity in detecting vulnerable
plaque.
CAN PERIPHERAL BLOOD BE USED TO IDENTIFY
VULNERABLE PLAQUES?
Several candidate markers in peripheral blood either
singly, or in combination identify patients at high
cardiovascular risk – LDL and oxidized LDL, C-reactive
proteins and other acute phase reactants, p-selectins,
monocyte chemoattractant protein-1 and macrophage colony
 Review
stimulating factor, CD-40 ligand, interleukins (1b and 6), 8 Antiplatelet agents (Aspirin/ Clopidogrel)
matrix metalloproteinases- to name a few. Pregnancy- 8 Others
associated plasma protein is a new marker for vulnerable - Peroxisome proliferator activated receptor agonists
plaque and is currently under extensive study [29]. - Anti-inflammatory agents
THERAPY FOR VULNERABLE PLAQUE - Antibiotics
Drugs (Plaque Stabilizers) - Antioxidants
8 HMG CoA reductase inhibitors Therapies that may possess plaque-
(Statins) stabilizing effects
8 Angiotensin converting enzyme Gene therapy
inhibitors (ACEI) 8 Metalloproteinase inhibitors
8 Antihypertensive agents 8 CD-40 pathway inhibitors
8 b-blockers Photodynamic therapy
8 w-3 fatty acids

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