Mechanisms of progression in native coronary artery disease: role of healed plaque disruption
J Mann, M J Davies
St George's
Hospital Medical School, British Heart Foundation Cardiovascular
Pathology Unit, Cranmer Terrace, London SW17 ORE, UK
Correspondence to: Professor Davies.
Accepted for publication 17 May 1999
OBJECTIVE
To determine
the role of healed plaque disruption in the generation of chronic high
grade coronary stenosis.
METHODS
Coronary
arteries obtained at necropsy were perfuse fixed with formal saline for
24 hours at 100 mg Hg. The percentage lumen diameter stenosis was
measured in each 3 mm segment containing a plaque, using the lumen
size at the nearest histologically normal segment as the reference
point. Each segment was prepared for histological examination and
stained with Sirius red and immunohistochemistry for smooth muscle
actin. Healed disruption was considered to be present when under
polarised light there was a break in the yellow-white dense collagen
of the cap filled in by more loosely arranged green collagen. Increased
smooth muscle density in the green staining areas was required. Each
section was read independently by two observers; any segment with
discordant views was considered negative.
MATERIAL
31 men aged
51-69 dying suddenly of ischaemic heart disease. 39 coronary arteries
were studied containing 256 separate plaques, after excluding coronary
arteries with old total occlusions, an acute culprit thrombotic lesion,
diffuse disease without normal arterial segments, and arteries related
to old myocardial scars.
RESULTS
16 of 99 plaques causing < 20% diameter stenosis had prior disruption. In the
21-50% stenosis range 16 of 86 plaques showed healed disruption.
Stenosis
51% by diameter was present in 71 plaques, 52 of which
showed a healed disruption pattern. The difference between stenosis
< 50% and stenosis
51% was significant by the
2
test (p < 0.001).
CONCLUSIONS
Subclinical
episodes of plaque disruption followed by healing are a stimulus to
plaque growth that occurs suddenly and is a major factor in causing
chronic high grade coronary stenosis. This mechanism would explain the
phasic rather than linear progression of coronary disease observed in
angiograms carried out annually in patients with chronic ischaemic
heart disease.
Keywords: atherosclerosis; stenosis; plaque disruption
© 1999 by Heart
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Braganza, D M, Bennett, M R
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[Full Text] -
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