(Circulation. 1996;93:1354-1363.)
© 1996 American Heart Association, Inc.
Articles |
From the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, and Office of the Chief Medical Examiner (J.S.), Baltimore, Md.
| Abstract |
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Methods and Results Fifty consecutive cases of sudden death due to coronary artery thrombosis were studied by histology and immunohistochemistry. Plaque rupture of a fibrous cap with communication of the thrombus with a lipid pool was identified in 28 cases. Thrombi without rupture were present in 22 cases, all of which had superficial erosion of a proteoglycan-rich plaque. The mean age at death was 53±10 years in plaque rupture cases versus 44±7 years in eroded plaques without rupture (P<.02). In the plaque-rupture group, 5 of 28 (18%) were women versus 11 of 22 (50%) with eroded plaques (P=.03). The mean percent luminal area stenosis was 78±12% in plaque rupture and 70±11% in superficial erosion (P<.03). Plaque calcification was present in 69% of ruptures versus 23% of erosions (P<.002). In plaque ruptures, the fibrous cap was infiltrated by macrophages in 100% and T cells in 75% of cases compared with 50% (P<.0001) and 32% (P<.004), respectively, in superficial erosions. Clusters of smooth muscle cells adjacent to the thrombi were present in 95% of erosions versus 33% of ruptures (P<.0001). HLA-DR expression was more often seen in macrophages and T cells in ruptures (25 of 28 cases) compared with expression in macrophages in superficial erosion arteries (8 of 22 cases, P=.0002).
Conclusions Erosion of proteoglycan-rich and smooth muscle cellrich plaques lacking a superficial lipid core or plaque rupture is a frequent finding in sudden death due to coronary thrombosis, comprising 44% of cases in the present study. These lesions are more often seen in younger individuals and women, have less luminal narrowing and less calcification, and less often have foci of macrophages and T cells compared with plaque ruptures.
Key Words: plaque thrombosis death, sudden coronary disease
| Introduction |
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A typical vulnerable plaque has been reported to consist of an eccentric plaque that is rich in extracellular lipid within a large lipid pool with a thin overlying fibrous cap.5 6 7 8 9 In these lesions, the fibrous cap is frequently infiltrated with activated T cells and macrophages. Plaque rupture of a thin fibrous cap resulting in exposure of flowing blood to the lipid core is believed to comprise the vast majority of coronary thrombi.1 2 This conclusion has emerged from studies of diverse populations that included individuals with sudden and nonsudden death with thrombi of different ages.10 11 12 13 14 15 16 17 18 19 20 21 The morphology of the underlying plaque associated with the thrombus has been examined in varying degrees of detail. The purpose of this study was to systematically describe the pathological substrate of coronary thrombosis in a defined group of individuals with sudden coronary death.
| Methods |
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Coronary Artery Evaluation
All hearts were examined fresh and uncut, with fixation
performed on the day of autopsy. No previously cut hearts were included
in this study. Hearts with a short segment of attached aortic stump
were excised and weighed. The coronary arterial
tree was perfusion-fixed with 10% neutral-buffered formalin
for 15 minutes at 100 mm Hg. Postmortem coronary angiography
was performed in most cases by selective injection of the left and
right ostium with a mixture of barium gelatin followed by
radiography after 15 minutes of further fixation. The
major epicardial coronary arteries (left main, left anterior
descending, left circumflex, and right coronary arteries) and
their main branches (left diagonals, left obtuse marginals, and
posterior descending coronary artery) were cut transversely at
2- to 3-mm intervals (following decalcification if necessary). Those
segments that had a >50% cross-sectional luminal stenosis
by visual inspection were submitted for light microscopy (after 24
hours of immersion-fixation in formalin),
histological examination, and morphometric
measurements. The severity and extent of coronary
atherosclerosis determined the number of
histological sections examined per case. Between one
and six arterial segments were placed in each cassette.
Arterial segments were dehydrated in a series of graded
alcohols, cleared with xylene, embedded in paraffin, cut at 4 µm, and
stained with hematoxylin-eosin and Movat pentachrome
stains. With Movat pentachrome, elastic fibers stain black,
collagen stains yellow, and proteoglycan stains green.
Coronary thrombosis cases were separated into two categories based on the morphology of the underlying plaque. (1) Coronary thrombosis with plaque rupture was defined as a disruption of a fibrous cap over a lipid core with contact of the acute thrombus with the lipid pool. (2) Coronary thrombosis with superficial erosion (without plaque rupture) consisted of an acute thrombus in direct contact with the intimal plaque without rupture of a lipid pool. A lipid core could be present deep within the plaque, but there could be no communication between the thrombus and lipid pool. Segments that demonstrated luminal thrombus but no rupture into a lipid core underwent serial step-sectioning and staining (at every 40 µm for at least 1 to 2 cm) to determine whether rupture of a fibrous cap was present deeper in the section.
Coronary artery segments that had an acute thrombus by light
microscopy (luminal collections of platelets and/or fibrin with or
without trapped erythrocytes and white blood cells) were selected for
immunohistochemical stains and morphometry. For immunohistochemical
stains, the avidin-biotin complex method was applied to
deparaffinized sections. The following antibodies (dilution in
parentheses) were used: smooth musclespecific
-actin
(1:5000, Sigma Chemical Co); KP-1, a macrophage marker (1:75,
Dako Corp); UCHL-1, a T-cell marker (1:75, Dako); HLA-DR, an antigen
expressed in activated cells (1:200, Dako); and factor VIII
(1:3200, Dako). For KP-1 and factor VIII, tissue sections were
predigested with protease K (0.1 mg/mL) at 37°C for 20 minutes.
Biotinylated rabbit or mouse IgG was used as the secondary antibody,
and the detection system was Vectastain Elite ABC kit (Vector
Laboratories). Sections were counterstained with hematoxylin. Positive
and negative controls were run in parallel for every stain.
The most severely narrowed arterial segment containing the thrombus was magnified and digitized. From this segment, the arterial size (defined by the area within the internal elastic lamina) and lumen area (excluding the thrombus) were measured (IPLab image analysis software, version 2.5) and used to determine cross-sectional area percent stenosis [100x(1-lumen area/arterial size)].
Myocardial Evaluation
The right and left ventricles were cut at 1.0-cm intervals
parallel to the posterior AV groove from apex to base. The
myocardium was examined for the presence of healed and/or
acute myocardial infarction. In hearts without gross evidence of
myocardial infarction (acute or healed), at least one section of the
myocardium was submitted (from the
mid-ventricular slice) from the anterior left
ventricular wall, lateral wall, posterior wall,
interventricular septum, and posterior right
ventricular wall (total of five myocardial sections). In
hearts with myocardial infarction identified on gross examination,
sections from all acute and healed infarcts in addition to the above
listed sections were submitted. Each myocardial section was
approximately 1.5- to 2.0-cm in length and extended from the
endocardium to epicardium. Healed myocardial infarction was identified
by focal macroscopic replacement of the myocardium by
scarring with histological confirmation. Acute
myocardial infarction was diagnosed by the presence of coagulation
necrosis of myocytes with or without an associated inflammatory
infiltrate.
Statistical Analysis
Numerical data are presented as mean±SD. Continuous
variables were compared with ANOVA, and categorical variables
were compared with a
2 test (Statview software,
version 4.01). A value of P
.05 was considered
significant.
| Results |
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The extent of epicardial coronary artery atherosclerosis was as follows: one-vessel disease in 28 (56%), two-vessel disease in 13 (26%), and three-vessel disease in 9 (18%). Of the 50 coronary arteries with acute thrombi, the left anterior descending was thrombosed in 33, left circumflex in 7, right coronary in 9, and ramus intermedius in 1. The mean percent cross-sectional area stenosis for all 50 arteries (excluding the thrombus itself) was 74±12% (range, 50 to 98%). An acute myocardial infarction was confirmed histologically in 16 cases (32%), of which 9 had only an acute infarct, and 7 had both an acute and healed infarct. A healed infarct in the absence of an acute infarct was present in 10 (20%), and no myocardial infarct (neither acute nor healed) was present in 24 cases (48%).
Coronary Pathology
Of the 50 acutely thrombosed coronary artery plaques,
there were 22 superficial erosions and 28 ruptures. In plaque rupture
cases (Figs 1
and 2
), a thin collagenous
fibrous cap separated the lumen from the underlying lipid core. The
plaque rupture site was characterized by discontinuity of the fibrous
cap and contact of the acute thrombus with the lipid core. The site of
rupture was in the center of the cap in 16 cases (57%), toward the
periphery of the cap (near the junction of the cap with the adjacent
intima) in 10 (36%), and indeterminate in 2.
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In coronary thrombosis without rupture into a lipid core (Figs 3 through 5![]()
![]()
), the plaque
luminal surface was irregular, eroded, and lacked
endothelial cells (negative factor VIII staining).
Occasionally, the erosion extended into the upper layers of the plaque
forming foci of intraplaque thrombi. The plaque in contact with the
thrombus was cellular and proteoglycan-rich (green staining with
Movat pentachrome stain). Deep to the cellular,
proteoglycan-rich luminal surface of the plaque, the plaque was
typically fibrous and hypocellular with variable foci of loose
collagen containing mononuclear cells. Lipid pools deep within the
plaque were occasionally seen; however, after serial
step-sectioning, in no case was there plaque rupture or
contact of the luminal thrombus with the deep lipid core. In all plaque
erosion cases in which the thrombus was nonocclusive, the thrombus
formed adjacent to the thickest portion of the plaque.
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In applying the definitions of advanced atherosclerotic lesions by the AHA Council on Atherosclerosis,23 all lesions (ruptures overlying a lipid pool and plaque erosions without lipid core rupture) are type VIc on the basis of the presence of an acute thrombus. However, the underlying plaque in the 28 cases with fibrous cap rupture would best fit a type IV. The underlying plaque in the superficially eroded arteries is more difficult to classify but can be viewed as a form of a type Va lesion (fibroatheroma) modified by the presence of abundant smooth muscle cells (see immunohistochemical staining results below) and proteoglycans.
Plaque Rupture Versus Superficial Erosion
The mean age in cases of coronary thrombosis due to plaque
rupture was 53±10 years versus 44±7 years in erosion
(P<.003; Table 1
). In the plaque-rupture
group, 5 of 28 (18%) were women versus 11 of 22 (50%) in eroded
plaques (P=.03). The mean percent cross-sectional area
stenosis (excluding the thrombus itself) was greater in
plaque-rupture group (78±12%) versus the eroded-plaque group
(70±11%, P<.03). The frequency distribution of luminal
narrowing is depicted in Table 2
. Plaque calcification
was present in 19 ruptures (69%) compared with 5 erosions (23%,
P=.002; Table 1
). The thrombus was occlusive in 12 rupture
cases (43%) and nonocclusive in 16 (57%); only 4 eroded plaques
(18%) demonstrated complete thrombotic occlusion (P=.08
versus rupture into a necrotic core). Thrombi were predominantly
composed of platelets in 13 (48%) plaque-rupture cases and of
fibrin in 15 (52%), a similar distribution to the eroded-plaque
group in which 14 (52%) were predominantly composed of platelets
and 8 (35%) were predominantly fibrin (P=.26). Increased
fibrin content may represent early organization of the thrombus
progressing from initial platelet deposition to infiltration and
stabilization by fibrin. Thirteen ruptured arteries (46%) were
concentric, and 15 (54%) were eccentric. Only 4 eroded arteries
without lipid core rupture (18%) were concentric, and the remaining 18
(82%) were eccentric (P=.07 versus rupture into a necrotic
core). An acute myocardial infarction was present in 10
coronary rupture cases (36%) compared with 6 erosion cases
(27%, P=.56). The frequency of healed myocardial infarction
was similar in coronary ruptures and erosions (11 [39%]
ruptures and 7 erosions [32%], P=.77).
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Immunohistochemical stains demonstrated several differences between
ruptures and erosions (Table 1
, Figs 1 through 5![]()
![]()
![]()
![]()
). Foci of
macrophages, identified by antiKP-1 staining, at the luminal
surface adjacent to the thrombus were present in all 28
plaque-rupture cases versus 11 plaque-erosion cases (50%)
(P<.0001). In plaque ruptures, macrophages
typically infiltrated the thin fibrous cap and were present
at the margins of the rupture site. When present in eroded plaques
without lipid core rupture, macrophages were sparsely
distributed in the upper layers of the plaque near the luminal surface.
Clusters of spindle-shaped cells, identified as smooth muscle cells
by actin staining, were seen at the luminal surface adjacent to the
thrombus in 21 plaque erosions (95%) compared with 11 cases (33%)
with smooth muscle cells in the fibrous cap adjacent to the plaque
rupture (P<.0001). T cells were present in 21 ruptured
plaques (75%) at the luminal surface in the vicinity of the rupture
site versus occasional scattered T cells in 7 eroded arteries (32%,
P<.004). Cell activation, indicated by HLA-DR staining, was
identified in macrophages and T cells in 25 plaque ruptures
(89%) and in macrophages in 8 plaque erosions (36%)
(P=.0002).
| Discussion |
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Few data are available on differences in plaque morphology between men and women. Cumulative coronary plaque composition studies by Dollar et al24 and Mautner et al25 have demonstrated increased cellular fibrous tissue and less calcified and dense fibrous tissue in women (17 hearts from women examined). The arteries studied had severe atherosclerosis without acute coronary thrombi. Cellular fibrous plaques are associated with an earlier stage of evolution of atherosclerotic lesions compared with dense hypocellular plaques24 25 ; however, smooth muscle content and distribution have not been specifically evaluated. In the present study, the mean ages of men and women were similar (49±9 and 49±13 years, respectively), and it is well established that the development of atherosclerosis is delayed in women, probably due to estrogen effects. Therefore, the increased frequency of smooth muscle cellrich plaques in women may be a function of plaque age. Thrombosis of smooth muscle cellrich plaques in younger individuals (compared with plaque ruptures) may represent a form of plaque progression in those who survive the thrombotic event.
The results in the present study are consistent with
previous serial angiographic studies that found that myocardial
infarction due to coronary occlusion often occurred in mildly
to moderately narrowed arteries on the initial
angiogram.3 4 The mean percent luminal area
stenosis of all thrombosed arteries (occlusive and nonocclusive
thrombi) in the present study was 74%, which corresponds (if we
assume a circular lumen) to an estimated diameter stenosis of
49%, ie, a moderate stenosis. Arteries that had an occlusive
thrombus were narrowed 77% by plaque (equivalent to a 52% diameter
stenosis). However, these histological
measurements are not directly comparable to angiography in which the
severity of stenosis is based on the diameter of the nearest
normal-appearing arterial segment that may or may not
have some degree of atherosclerosis. Previous autopsy
studies have shown that occlusive thrombi are typically found in
severely stenosed arteries (luminal area narrowing
90%16 26 ). Differences between these results and those
of the present study may be explained by the differences in the
populations; in the present study, individuals presented
with sudden coronary death and only 32% had
histological evidence of an acute myocardial infarction
versus individuals with well-established infarcts26 or
with thrombi of varying ages.16 Our data suggest that both
occlusive and nonocclusive coronary thromboses are important
causes of sudden death.
Previous Studies of Coronary Thrombosis
Since the recognition that acute ischemic syndromes (acute
myocardial infarction, unstable angina, and sudden coronary
death) are often precipitated by coronary atherosclerotic
plaque disruption and thrombosis, a search for thrombus-prone
plaques has progressed over several decades. Davies and
Thomas1 have concluded that nearly all
coronary thrombi leading to fatal myocardial infarction are
associated with plaque rupture in which there is contact between
luminal blood and the lipid core of the plaque. Falk2 has
similarly stated that ruptured plaques account for >75% of fatal
coronary thrombi with the thrombus typically associated with
displaced atheromatous plaque material. In Falk's
experience, only
20% of thrombi examined at postmortem demonstrated
minor or superficial intimal injury, usually in combination with severe
underlying atherosclerotic stenosis, without rupture into a
lipid pool. However, in previous studies (as detailed below),
coronary morphology associated with thrombi of varying ages has
been examined from a diverse population of sudden and nonsudden cardiac
deaths. One could speculate that different ages of thrombi may affect
arterial morphology as the thrombus organizes.
Studies of Combined Sudden and Nonsudden Death
Friedman and Van Den Bovenkamp10 found that 30 of 40
occlusive coronary thrombi were associated with direct
communication of the thrombus with intraplaque
atheromatous abscesses with the site of rupture
infiltrated with lipid-laden macrophages. In this study of
40 patients, 93% were men, of which only 11 (28%) died suddenly, and
the remainder died between 1 and 28 days after the onset of chest pain,
dyspnea, or collapse. Constantinides12 examined 17
coronary arteries with "recent" thrombi, and all 17 had
cracks in the atherosclerotic plaque wall. No data on patient
characteristics were provided. Chapman13 reported on 19
recent occlusive coronary thrombi, all of which had direct
contact with atheromatous debris. No data were provided
on patient characteristics or clinical presentation.
Ridolfi and Hutchins14 studied 17 thrombosed
coronary arteries associated with myocardial infarction <48
hours old; 16 had intimal erosion, plaque erosion, or ruptured plaque.
Coronary arteries from 108 patients with acute myocardial
infarction were examined by Horie et al15 ; sudden death
cases without myocardial necrosis were excluded. Only 18 (17%) died
within 24 hours of acute infarction. A ruptured plaque was noted in 69
of 76 thrombosed coronary arteries (91%).
In a detailed coronary morphology study of plaque disruption
and coronary thrombosis, Falk16 performed
postmortem examination on 44 cases of sudden and nonsudden
coronary death. He found 103 ruptured plaques defined as
disruption of a fibrous cap resulting in contact of blood with
pultaceous debris of a lipid core. Of these 103, 63 had intimal
hemorrhage without luminal thrombus, and 40 had luminal
thrombus (38 of 40 occlusive). Forty of 49 recently thrombosed arteries
(82%) had plaque rupture, and the ruptured cap was always thin and
usually infiltrated by foam cells. There were 11 cases with occlusive
thrombosis and intimal irregularities but no plaque rupture; 9 of these
11 had a
90% luminal area stenosis. Differences between the
present study and the study by Falk16 may be due to
patient selection; 49% of the thrombi were interpreted to be greater
than 24 hours old (from 1 day to
2 weeks) so that interval changes in
plaque morphology may have occurred. Further, the patients from Falk's
study were all hospital-based (compared with medical examiner's
cases in the present study) and were older (mean age, 69
years).
Tracy et al18 examined 21 longitudinally sectioned thrombosed coronary arteries from 18 hearts selected on the basis of the presence of acute thrombosis on gross inspection. Data on sudden versus nonsudden death were not provided. All arteries had a necrotic core, and 86% had plaque rupture. Cliff et al19 studied 25 cases of sudden coronary death and 9 cases of death within 14 days of myocardial infarction. All cases were in men, and there were 10 occlusive and 4 mural thrombi. Pultaceous material was identified in 33 of 34 cases (97%), but there was no mention of any association with plaque disruption or communication of the intraluminal thrombus with a lipid core. Richardson et al20 examined 85 arterial segments with recent thrombi containing platelets and fibrin and plaque fissures defined by postmortem angiography. There were 71 arteries (84%) with a lipid pool; 67 of these 71 had fissure extension into an eccentric lipid core, and 4 had a concentric lipid pool with an intimal tear. Foam cells were present at the tear site in 53 of 71 (75%). Fourteen arterial segments (17%) had an intimal fissure without rupture into a lipid pool. Patient characteristics and circumstances at the time of death (sudden versus nonsudden death) were not provided.
Studies Limited to Sudden Death
Among 37 sudden death cases, Friedman et al11
identified 20 acute coronary thrombi, 19 of which had luminal
plaque rupture and an underlying focus of necrotic plaque. Men
comprised 89% of the 37 individuals examined, consistent with
the finding of 82% men in the plaque-rupture group in the
present study. Davies and Thomas17 identified
intraluminal thrombi in 74% of 100 consecutive cases. The mean percent
cross-sectional luminal stenosis was 79% in arteries with
luminal thrombi. Of the 74 thrombi, 90% were associated with plaque
fissuring, but it is unknown how many arteries had direct contact of an
acute thrombus with a ruptured lipid core. When thrombi occurred in
arteries with <50% stenosis (14 of 74 cases), a major fissure
of a lipid-rich plaque was seen. Data on patient age and sex
distribution were not provided. Morphology similar to the smooth muscle
cellrich and proteoglycan-rich plaques observed in the
present study were not reported by either Friedman et
al11 or Davies and Thomas.17
Inflammatory Cells and Smooth Muscle Cells in
Coronary Thrombosis
The role of inflammation in coronary thrombosis was
previously explored by van der Wal et al.27 They studied
20 thrombosed coronary arteries from patients dying within 1
day of a pathologically confirmed myocardial infarct. There were 12
deep plaque ruptures extending into a lipid core and 8 superficial
erosions defined as an eroded plaque surface with loss of
endothelial cells and superficial intimal injury but no
cap rupture or intraplaque hemorrhage. In ruptures, the rupture
site contained abundant HLA-DRpositive macrophages and T
cells, which is similar to the results in the present study.
However, in their 8 erosion cases, smooth muscle cells were absent, and
HLA-DRpositive macrophages and T cells were contiguous with
the thrombus. They did note HLA-DRpositive smooth muscle cells in the
connective tissue beneath the plaque surface in 6 erosions. In
contrast, in the present study, a morphologically distinct lesion
was identified; superficial erosions demonstrated abundant smooth
muscle cells at the luminal surface, HLA-DRpositive
macrophages were present in only 8 cases (36%), and
inflammatory cells were sparse. On the basis of these findings, we
would categorize the smooth muscle cellrich thrombotic plaques in
the present study as noninflammatory erosions. Because of the
paucity of inflammatory cells in these eroded arteries, plaque
inflammation may play a smaller role in the development of acute
thrombosis compared with plaque ruptures.
Smooth muscle cell proliferation within the intima plays a central role in the development of atherosclerotic plaque.28 In addition to intraluminal thrombi and plaque rupture,1 29 30 31 32 smooth muscle cellrich plaques, obtained by directional atherectomy, have been frequently seen in patients with unstable angina.33 To the best of our knowledge, the present study is the first to demonstrate an association between smooth muscle cell foci at the luminal surface and acute coronary thrombosis. In the eroded coronary arteries that lacked rupture into a lipid core, the plaque luminal surface was irregular and lacked endothelial cells. We postulate that endothelial injury leads to platelet deposition followed by plaque smooth muscle proliferation and extracellular matrix synthesis. This hypothesis may be considered a modification of Ross's "response-to-injury" theory of the development of atherosclerotic plaque.34 The response-to-injury model as originally proposed attempted to explain plaque growth in a normal artery rather than coronary thrombosis of an artery with an advanced plaque. We propose that chronic endothelial loss over an atherosclerotic plaque increases the risk of arterial thrombosis.
Smooth muscle cells synthesize the bulk of the connective tissue in atherosclerotic plaque,35 and the presence of proteoglycan-rich plaque at the luminal surface in thrombosed eroded coronary arteries may be important in the mechanism of thrombosis. The main proteoglycans that comprise the extracellular matrix in vascular structures are enriched in chondroitin sulfate, dermatan sulfate, and heparan sulfate.36 In the development of atherosclerotic lesions, there is a progressive accumulation of chondroitin sulfate and dermatan sulfate with no change or a reduction in heparan sulfate.36 37 38 Heparan sulfate is an anticoagulant39 and inhibits thrombin-induced platelet aggregation.40 The procoagulant platelet factor 4 (PF4) is a heparin antagonist and is complexed to chondroitin sulfate.36 41 In vitro studies demonstrate competitive binding of heparin and PF4 to the surface of endothelial cells.42 The inactivation of thrombin by antithrombin III may be dependent on its binding to heparan sulfate on the surface of endothelial cells.43 One could speculate that changes in the distribution and composition of proteoglycans (ie, reduced heparan sulfate and increased chondroitin sulfate content) may contribute to coronary thrombosis via reduced inhibition of the clotting cascade.
The results of the present study underscore the heterogeneity of atherosclerotic plaques in sudden coronary thrombosis and support the concept that multiple mechanisms are likely to be involved in thrombus formation. Certain hemodynamic factors such as bending and twisting of the coronary arteries during the cardiac cycle, pulse pressure, vasomotion/spasm, and increased shear stress at the site of stenosis may be responsible for increasing the likelihood of endothelial damage and acute thrombosis in atherosclerotic arteries.5 Within the plaque itself, the presence of tissue factor and plasminogen activator inhibitor1 may augment the thrombotic potential of an atherosclerotic lesion.44 45 Increased circulating levels of hemostatic factors such as fibrinogen, von Willebrand factor, and tissue plasminogen activator antigen have been shown to be independent predictors of acute coronary syndromes.46 It should not be surprising that plaque morphologies may differ in acute thrombosis, and future studies are needed to determine whether certain hemostatic factors, hemodynamic profiles, and/or risk factors for the development of atherosclerosis can be associated with plaque rupture or erosion.
Study Limitations
As an autopsy study, the results presented may not be
representative of persons who develop coronary
thrombosis and survive. Furthermore, all cases in the present study
are from individuals with sudden death so that the findings may not be
applicable to coronary thrombi associated with other acute
ischemic syndromes (acute myocardial infarction or unstable
angina).
Conclusions
By critical examination of the underlying plaque in acute
coronary thrombosis, the present study expands the
definition of thrombus-prone plaques to include smooth muscle
cellrich and proteoglycan-rich plaques associated with
chronic endothelial loss. The data presented
suggest that rupture of a thin fibrous cap overlying a lipid core is
not necessarily the only final common pathway in the formation of
coronary thrombi.
| Footnotes |
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The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the US Department of the Army or the US Department of Defense.
Received August 28, 1995; revision received November 1, 1995; accepted November 3, 1995.
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M. Naghavi, P. Libby, E. Falk, S. W. Casscells, S. Litovsky, J. Rumberger, J. J. Badimon, C. Stefanadis, P. Moreno, G. Pasterkamp, et al. From Vulnerable Plaque to Vulnerable Patient: A Call for New Definitions and Risk Assessment Strategies: Part I Circulation, October 7, 2003; 108(14): 1664 - 1672. [Abstract] [Full Text] [PDF] |
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L. J. Shaw, P. Raggi, E. Schisterman, D. S. Berman, and T. Q. Callister Prognostic Value of Cardiac Risk Factors and Coronary Artery Calcium Screening for All-Cause Mortality Radiology, September 1, 2003; 228(3): 826 - 833. [Abstract] [Full Text] [PDF] |
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T. Sano, A. Tanaka, M. Namba, Y. Nishibori, Y. Nishida, T. Kawarabayashi, D. Fukuda, K. Shimada, and J. Yoshikawa C-Reactive Protein and Lesion Morphology in Patients With Acute Myocardial Infarction Circulation, July 22, 2003; 108(3): 282 - 285. [Abstract] [Full Text] [PDF] |
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J.-i. Kotani, G. S. Mintz, M. T. Castagna, E. Pinnow, C. O. Berzingi, A. B. Bui, A. D. Pichard, L. F. Satler, W. O. Suddath, R. Waksman, et al. Intravascular Ultrasound Analysis of Infarct-Related and Non-Infarct-Related Arteries in Patients Who Presented With an Acute Myocardial Infarction Circulation, June 17, 2003; 107(23): 2889 - 2893. [Abstract] [Full Text] [PDF] |
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A. P. Burke, R. Virmani, Z. Galis, C. C. Haudenschild, and J. E. Muller Task force #2--what is the pathologic basis for new atherosclerosis imaging techniques? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1874 - 1886. [Full Text] [PDF] |
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F. Trostdorf, M. Sitzer, B. Chambers, J. Stork, K. Kimura, A. Abbott, C. Levi, and G. Donnan Symptomatic Carotid Artery Stenosis: Heterogeneity of Destabilizing Mechanisms? * Response Stroke, June 1, 2003; 34 (6): e41 - e41. [Full Text] [PDF] |
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H. Tomoda and N. Aoki Clinical Evaluation of Coronary Lesion Characteristics in Acute Myocardial Infarction Angiology, May 1, 2003; 54(3): 277 - 285. [Abstract] [PDF] |
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C. Heeschen, S. Dimmeler, C. W. Hamm, S. Fichtlscherer, E. Boersma, M. L. Simoons, A. M. Zeiher, and for the CAPTURE Study Investigators Serum Level of the Antiinflammatory Cytokine Interleukin-10 Is an Important Prognostic Determinant in Patients With Acute Coronary Syndromes Circulation, April 29, 2003; 107(16): 2109 - 2114. [Abstract] [Full Text] [PDF] |
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P. Cullen, R. Baetta, S. Bellosta, F. Bernini, G. Chinetti, A. Cignarella, A. von Eckardstein, A. Exley, M. Goddard, M. Hofker, et al. Rupture of the Atherosclerotic Plaque: Does a Good Animal Model Exist? Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 535 - 542. [Abstract] [Full Text] [PDF] |
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C. Heeschen, S. Dimmeler, C. W. Hamm, M. J. van den Brand, E. Boersma, A. M. Zeiher, M. L. Simoons, and the CAPTURE Study Investigators Soluble CD40 Ligand in Acute Coronary Syndromes N. Engl. J. Med., March 20, 2003; 348(12): 1104 - 1111. [Abstract] [Full Text] [PDF] |
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P. K. Shah Mechanisms of plaque vulnerability and rupture J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 15S - 22S. [Abstract] [Full Text] [PDF] |
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M. Valgimigli, L. Agnoletti, S. Curello, L. Comini, G. Francolini, F. Mastrorilli, E. Merli, R. Pirani, G. Guardigli, P. G. Grigolato, et al. Serum From Patients With Acute Coronary Syndromes Displays a Proapoptotic Effect on Human Endothelial Cells: A Possible Link to Pan-Coronary Syndromes Circulation, January 21, 2003; 107(2): 264 - 270. [Abstract] [Full Text] [PDF] |
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D. Proudfoot, J.D. Davies, J.N. Skepper, P.L. Weissberg, and C.M. Shanahan Acetylated Low-Density Lipoprotein Stimulates Human Vascular Smooth Muscle Cell Calcification by Promoting Osteoblastic Differentiation and Inhibiting Phagocytosis Circulation, December 10, 2002; 106(24): 3044 - 3050. [Abstract] [Full Text] [PDF] |
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M. E. Bertrand, M. L. Simoons, K. A.A. Fox, L. C. Wallentin, C. W. Hamm, E. McFadden, P. J. De Feyter, G. Specchia, and W. Ruzyllo Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation Eur. Heart J., December 1, 2002; 23(23): 1809 - 1840. [Full Text] [PDF] |
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A. P. Burke, V. Fonseca, F. Kolodgie, A. Zieske, L. Fink, and R. Virmani Increased Serum Homocysteine and Sudden Death Resulting from Coronary Atherosclerosis With Fibrous Plaques Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1936 - 1941. [Abstract] [Full Text] [PDF] |
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F. D. Kolodgie, A. P. Burke, A. Farb, D. K. Weber, R. Kutys, T. N. Wight, and R. Virmani Differential Accumulation of Proteoglycans and Hyaluronan in Culprit Lesions: Insights Into Plaque Erosion Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1642 - 1648. [Abstract] [Full Text] [PDF] |
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A. Maehara, G. S. Mintz, A. B. Bui, O. R. Walter, M. T. Castagna, D. Canos, A. D. Pichard, L. F. Satler, R. Waksman, W. O. Suddath, et al. Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound J. Am. Coll. Cardiol., September 4, 2002; 40(5): 904 - 910. [Abstract] [Full Text] [PDF] |
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P.J. Gallagher More histological information in acute coronary death Eur. Heart J., September 2, 2002; 23(18): 1406 - 1408. [Full Text] [PDF] |
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R. Henriques de Gouveia, A.C. van der Wal, C.M. van der Loos, and A.E. Becker Sudden unexpected death in young adults. Discrepancies between initiation of acute plaque complications and the onset of acute coronary death Eur. Heart J., September 2, 2002; 23(18): 1433 - 1440. [Abstract] [Full Text] [PDF] |
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R. Erbell, T. Budde, G. Kerkhoff, S. Mohlenkamp, and A. Schmermund Understanding the pathophysiology of the arterial wall: which method should we choose? Electron beam computed tomography Eur. Heart J. Suppl., September 1, 2002; 4(suppl_F): F47 - F53. [Abstract] [PDF] |
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G Pasterkamp and R Virmani The erythrocyte: a new player in atheromatous core formation Heart, August 1, 2002; 88(2): 115 - 116. [Full Text] [PDF] |
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L. L Demer Vascular calcification and osteoporosis: inflammatory responses to oxidized lipids Int. J. Epidemiol., August 1, 2002; 31(4): 737 - 741. [Full Text] [PDF] |
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A. K. Majors, S. Sengupta, B. Willard, M. T. Kinter, R. E. Pyeritz, and D. W. Jacobsen Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1354 - 1359. [Abstract] [Full Text] [PDF] |
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R. P. Choudhury, V. Fuster, J. J. Badimon, E. A. Fisher, and Z. A. Fayad MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1065 - 1074. [Abstract] [Full Text] [PDF] |
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J. A. Ambrose and E. E. Martinez A New Paradigm for Plaque Stabilization Circulation, April 23, 2002; 105(16): 2000 - 2004. [Abstract] [Full Text] [PDF] |
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A. B. Newman, B. L. Naydeck, J. Whittle, K. Sutton-Tyrrell, D. Edmundowicz, and L. H. Kuller Racial Differences in Coronary Artery Calcification in Older Adults Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 424 - 430. [Abstract] [Full Text] [PDF] |
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