| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1997;96:1145-1151.)
© 1997 American Heart Association, Inc.
Articles |
Evidence of Multifocal Activity of Coronary Disease in Patients With Acute Myocardial Infarction
From Istituto di Cardiologia dell'Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Fondazione "Monzino," I.R.C.C.S., Milan, Italy.
Correspondence to Maurizio Guazzi, MD, PhD; Istituto di Cardiologia, Via C. Parea, 4, 20138 Milano, Italy.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background Destabilization of the fibrous cap facilitates plaque rupture, thrombus formation, and myocardial infarction. Because systemic stimuli, such as lipoproteins, infectious agents, and autoantigens, may incite this reaction, one may wonder whether disruption mechanisms are only local or systemic and infarction is caused by an arbitrary plaque event or by a systemic, acute activity of the coronary disease.
Methods and Results Early (3 to 5 days) and late (1 month) peri-infarction coronary angiographic data in 23 patients with first infarction were compared with that in 23 similar patients, with angiography performed because of stable angina and repeated after 1 month before angioplasty. Nonculprit lesion changes at the narrowest point defined progression or regression when exceeding 0.27 mm. In patients with recent infarction we found that 16 had progression, 4 had regression, 1 had both, 2 were steady (values in patients with stable angina being 2 [P<.001], 1 [NS], 0 [NS], and 20 [P<.001]); 27 lesions were infarct related; 17 of the 45 nonculprit lesions progressed and 5 regressed (values in stable angina being 2 [P<.001] and 1 [P<.05] out of 78); minimal diameter reduction of progressing stenoses averaged 0.39 mm; lumen increase of regressing lesions averaged 0.30 mm; 3 patients developed interim rest angina associated with progression of a nonculprit lesion.
Conclusions A greater proportion of subjects and lesions with progression or regression (in infarction versus stable angina) supports the hypothesis that infarction is a hallmark of systemic coronary disease activity. Changes might vary according to the "maturation" stage of an atheroma, and maximal expression would be at the level of the offending plaque. Shrinkage, thrombolysis, or vascular remodeling would determine the residual plaque morphology.
Key Words: plaque • angina • myocardial infarction • remodeling
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
There are compelling reasons to believe that rupture or fissuring of atheromatous plaques plays a major role in acute myocardial infarction as well as in lesion progression.1 2 3 4 5 6 Subclinical episodes of plaque disruption with local thrombin activation and subsequent reseal with incorporation of the thrombus into the vessel wall may indeed represent a major pathway for episodic progression superimposed on the slower systemic process.3 7
The degree of encroachment on the arterial lumen probably is not the unique or the main factor that renders plaque susceptible to disruption, because lesions that are most likely to precipitate an infarct-provoking thrombosis often do not appear highly stenotic at angiography.4 5 6 In addition to biomechanical factors such as circumferential stress,2 8 shear stress,9 and banding and twisting during the cardiac cycle and vasospasm,6 10 several recent morphological, biochemical, immunological, molecular, and vascular biology studies3 11 12 13 14 15 16 17 indicate a crucial role of destabilizing changes in the fibrous cap (a localized inflammatory or immunological process) causing local weakening of the plaque, which results in the rupture. Lipoproteins or their derivatives (eg, cytotoxicity from oxidized lipoproteins) may incite this ongoing reaction; other potential stimuli include infectious agents or autoantigens.3 11 Thus, the question may arise as to whether the predominant mechanisms for plaque disruption are local and occur at a single plaque or are systemic and occur at multiple plaques and whether myocardial infarction is the manifestation of a random or arbitrary plaque event or is the more advanced signal of a systemic activity of the coronary disease with multifocal lesion involvement.
A prospective, quantitative coronary angiographic study with angiography performed at an early and a late peri-infarction phase was undertaken to probe this hypothesis.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients With Acute Infarction
Patients who underwent coronary angiography at the time of their hospitalization in the coronary care unit for first myocardial infarction were eligible to participate in the study if they were under 66 years of age. Infarction was defined by characteristic pain lasting >30 minutes accompanied by evolving ST-T wave changes or development of abnormal Q waves on the ECG and by elevation of creatine kinase to twice the upper normal limit. Angiography was performed from 3 to 5 days after the acute event because of the decision made by the private physician caring for the patient (9 cases) or as "standard practice" in subjects aged <55 years (these were 14 consecutive cases). Predetermined grounds for exclusion were cardiac failure, malignancy, other major organ disease, diabetes, or hypertension. Patients were also excluded if they had previously undergone coronary artery revascularization. The nature and the purpose of the trial were described, and patients were included in the study if written informed consent was expressed to undergo repeat elective coronary angiography in accordance with the guidelines established by the Committee for the Protection of the Human Subjects. Patients who were judged as unable to understand the implications of the trial were excluded. A total of 30 patients were eligible and enrolled for late angiography; a history of long-term stable angina was obtained from 20% of cases (in the remaining patients angina was of recent onset); 84% had been subjected to early thrombolysis. Two patients refused to undergo another angiographic procedure, 1 was lost to follow-up, and coronary angiography was deemed clinically contraindicated in 2 patients because of interim development of cardiac failure. Matched control subjects for these patients were excluded.
Control Patients
A second group of patients with persistent stable angina had
coronary angiography that was repeated during angioplasty. All
had positive results on exercise testing and no changes in symptoms in
the preceding 5 months. Criteria for exclusion were those already
described for the other group. A history of acute chest pain at rest in
the past with significant Q waves in more than one ECG lead or
segmental left ventricular wall motion abnormality were
additional reasons for exclusion from the study. Two hundred eight
patients constituted the pool of control subjects.
Matching
Four variables were used to match 30 patients from the pool
of control subjects to the 30 patients with first myocardial
infarction: (1) sex, (2) patient age, (3) smoking habit, and (4) total
cholesterol plasma concentration. Matching was exact for
variables 1 and 2 and was made to the nearest available control
subject for variables 3 and 4. The nearest available matching was
performed with the use of a multivariate linear
discriminant function.18 Among control subjects, repeated
angiography was part of elective angioplasty; 2 refused to undergo
another angiographic procedure. Thus, angiographic follow-up was
obtained in 23 patients in each group, who constitute the substance of
this report. Their demographic and clinical characteristics are
reported in Table 1
.
|
Medical Therapy and Follow-up
Patients were told that use of sublingual
nitroglycerin was desirable at the onset of chest pain
and before engaging in major physical activities. They were also
informed that stopping smoking was a fundamental requirement, and
current smokers were strongly encouraged to do so. None followed a
medically controlled physical training program in the interval between
the two studies. During the interval, patients were receiving nitrates,
ß-blockers, ACE inhibitors, and antiplatelet agents
alone or in combination, as needed; lipid-lowering and calcium
antagonistic drugs19 20 21 were not part of the
regimen. Patients and control subjects underwent repeat
coronary angiography 1 month after enrollment. The study
protocol was approved by the institution ethics committee.
Coronary Angiography and Image Analysis
We used the Judkins percutaneous femoral artery
technique for coronary angiography, with routine use of
nitroglycerin to optimize coronary
vasodilatation. Multiple views of the right and left coronary
arteries were routinely recorded (Siemens-Elema equipment with a
C-arm) at 60 frames/s, by use of an intensifier with a
1-cm2 grid for correction of pincushion distortion. Viewing
angles and sequence of view were recorded and reproduced at repeat
angiography. Coronary artery stenoses were
analyzed if the view was clear and unobstructed and the
narrowing was clearly seen in at least two different views. Paired
coded films were compared and paired frames of the same view at end
diastole were coded and marked to identify the segments for
image analysis. Coding was done by an investigator who was
blinded to the study group; image analysis was done by
investigators who were blinded to the sequence and patient group of the
angiograms. Quantitative assessment was carried out by use of a
validated computer-assisted system (Quantum IC, software, Image Comm)
by which coronary lumen diameters were measured with an
automated edge-contour detection system. We derived the percent
stenosis diameter and calculated absolute lumen diameter (in
millimeters) of each narrowing. The dimension (micrometry) of the
Judkins catheter stem was used for calibration to determine absolute
measurements. Orthogonal views were not measured and averaged because
it is accepted that measurement of the view showing the
stenosis at its most severe is sufficient.22
Percent diameter reduction of a coronary stenosis was
calculated on the basis of the diameter of the stenosis at its
most severe; the diameter of the reference segment (a normal segment
proximal to the lesion) was measured in millimeters.
Two independent experienced investigators, blinded to the patient's identity and group and to the sequence of the angiograms, classified each stenosis as "complex" (with irregular borders, overhanging edges, and/or showing ulceration or superimposed nonocclusive thrombus, not necessarily eccentric23 ) or "smooth" (eccentric or concentric narrowing with smooth edges, without complex features). In two cases of discrepancy, a third investigator was involved and classification was made by consensus.
The infarct-related artery was determined from the admission ECG, wall motion abnormality, and possible presence of residual thrombus in the artery. The culprit stenosis of the infarct-related artery was defined as either the most severe proximal stenosis or a proximal stenosis identified with an occlusive thrombus. In 4 patients with two similarly severe narrowings in the same infarct-related vessel, a single culprit lesion could not be identified.
Measures of Evolution
Change in the arterial lumen diameter at the
narrowest point of the nonculprit lesions was the principal end point
measure. Secondary angiographic end points were the changes in percent
diameter stenosis and morphology and the development of a new
lesion. The definition of disease progression and regression took into
account the variability of repeated analysis of
arterial stenoses. We adopted the method validated
by Gibson et al24 and defined progression or regression as
a change in the minimal coronary artery diameter >0.27
mm. Criteria for new lesions were the development of a luminal
narrowing 
20% in which no obstruction was discernible at
the first catheterization.
Statistical Methods
Within-subjects ANOVA and unpaired or paired Student's
t test as appropriate were used to analyze the data.
Differences in the proportion of patients and lesions showing
progression or regression were compared by the 
2
and Fisher's exact test. Values are expressed as mean±SD. A value of
P<.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
Forty-six patients completed the study. At baseline there were no significant differences in the characteristics shown, and risk factors were well balanced between study and control groups. Although not considered in the matching process, HDL and LDL cholesterol plasma concentrations were also balanced.
Coronary Angiographic Data
Findings at first catheterization are given in Fig 1. The number of narrowings
was similar in the two groups, with a mean of 3.2 and of 3.4 lesions
per patient in the study and in the control population, respectively
(P=NS). Occluded segments (12 versus 3) and patients with
occlusion (12 versus 3) were more numerous in the infarction group. In
the same, 27 lesions were identified as infarct related; 15 of them
were not occluded. At restudy the number of stenoses was
unchanged in either group and no new narrowing was apparent. Lesions
causing >50% lumen reduction were slightly increased in the
infarction group without reaching statistical significance.
|
No significant difference was detected in the early (2.71±0.98
mm) and late diameter (2.76±0.97 mm) measurements of the normal
reference segments proximal to the lesions (P=NS).
Stenosis progression could be seen in 2 control patients (one
>50% lesion in each) and regression in 1 control patient (one <50%
lesion). In the remaining 20 subjects in this group, no differences
were noted between initial and later catheterization
(Table 2). Patients and
lesions with progression in the infarction group were 70% and 38%,
respectively, and significantly exceeded those in the control group
(Table 2). Among the infarction patients, 4 had regression (one lesion
in each) and 1 showed both regression and progression. Two patients
showed angiographic steadiness (90% less than in the control
group).
|
)
Fig 2 reports the arterial lumen diameter (in millimeters)
at the narrowest point of each "smooth" and "complex"
progressing and regressing lesion, as detected at the first and the
second angiography; culprit lesions in the study patients were not
included in this
analysis. Seventeen of
45 nonculprit stenoses progressed in the infarction group,
making a significant difference from the control population, in which
progressive narrowings were only 2 of 78. At repeated angiography, the
mean minimal lumen diameter of the progressing and regressing
stenoses in the study patients was reduced by 0.39 mm and
augmented by 0.30 mm, respectively. Fig 3 shows that among the
study patients, minimal luminal diameter was reduced from 12% to 45%
in the nonculprit progressing lesions and augmented from 7% to 30% in
the regressing ones. As to the
morphology, 10 lesions were "smooth" and 7 were "complex"
at first angiography; at repeated angiography corresponding figures
were 5 and 12. Although a definite pattern could not be established
regarding complexity and stenosis progression, it is
significant that all regressing lesions lost complexity (Fig 2), that
acquisition or persistence of complexity was predominant among the
progressing lesions (Fig 2), and that the greater percent reductions of
the narrowest arterial lumen were associated with
complexity (Fig 3).
|
|
The pattern of the infarct-related plaques is detailed in Fig 4. None of the 12 totally
occluded lesions at the first angiography became patent in the study
interval. Among the patent lesions, the mean diameter at the narrowest
point reduced from 0.89 to 0.75 mm (P=NS), 1 improved,
9 were steady, 4 worsened, and 1 became fully occluded; worsening was
shared by nonculprit lesions in the same patients.
|
Clinical Data
None of the subjects with stable angina had interim clinical
events or modifications in anginal symptoms,
nitroglycerin consumption, or ECG pattern at rest or on
exercise. In them, the use of ACE inhibitors, ß-blockers,
nitrates, and antiplatelet agents during follow-up was not
significantly different from that in the infarction group (Table 3). In the 1-month follow-up
there were also no significant differences in lipid values for patients
in both groups having progression, regression, or steadiness of the
disease (Table 4). All current
smokers in the infarction group and 9 of 13 in the control group quit
smoking.
|
|
The erythrocyte sedimentation rate in infarction patients with
progression and in those with regression or steadiness of the disease
was similar at first angiography and significantly higher in the former
at repeat angiography (Fig 5).
Sedimentation rate in the group of control subjects averaged 8.8±4.2
and 7.9±3.7 mm at first and second coronary angiography,
respectively.
|
Three of the study patients developed angina at rest in the interval
between angiograms. In each, repeated angiography showed no changes in
the infarct-related lesion and significant progression of a nonculprit
lesion (Figs 2
and 3). The clinical course was uneventful in the other
patients.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Matching from the pool of control subjects was exact for sex and age; smoking habit, lipids, and cardiac medications were well balanced both before and during the follow-up. The mean number of coronary lesions per patient was also comparable in the infarction group as in the stable angina group. This seems at variance with findings of Bogaty et al,25 but the different proportion of women, 20% versus 4% in our population, could considerably affect the discrepancy.
Despite these similarities, the proportion of subjects and lesions with progression and the degree of progression were strikingly greater in patients experiencing the first acute myocardial infarction. That the angiographic pattern in these patients was indeed a peculiar one is supported by a number of considerations. Those performing analyses were experienced in angiographic interpretation and were the same for the two groups. Early and late diameter measurements of the normal reference segments proximal to the lesions were comparable, and, within the same patient, narrowings other than the progressing or regressing ones showed the same lumen dimensions in the two angiograms. This makes it unlikely that differences could be attributed to a systematic error or a variable vasoconstriction at the site of stenosis. Finally, even though a relatively short-term follow-up carried out by Kaski and collaborators26 has shown that evolution of coronary disease in long-term stable angina may be less slow than demonstrated in previous long-term studies,27 28 it is remarkable that in the Kaski study, patients were specifically excluded if the interval between angiographies was less than 2 months.
Bemis et al29 found progression in 52% of 73 coronary patients who were reconsidered after an average interval of 23.8 months and in 14 out of 15 surviving an interval myocardial infarction. In 200 patients with ischemic heart disease, Kramer et al30 reported progression at an interval of 36.5 months in 65% of those who had interim infarction compared with 44% among those who had not. Angiographic reevaluations have shown an enhanced progression of the disease in unstable angina26 27 28 31 ; unfortunately, unstable angina is not synonymous with acute myocardial infarction, and the intervals from the initial angiogram were much longer than in our study and averaged 44,27 15,28 and 826 31 months, respectively. It is unfortunate that peri-infarction repeated angiographies32 were aimed only at investigation of early remodeling of the offending lesion after thrombolysis and that only thrombosed coronary arteries that correlated with recent transmural myocardial infarction were selected for an analysis of plaque morphology in patients who died of acute myocardial infarction.14 Falk,33 in a postmortem study of 44 patients with acute fatal myocardial infarction, found 51 recent coronary thrombi.
Several points bespeak participation of systemic factors in acute coronary occlusion and a possible association of this with multiple plaque involvement. Half of the patients connect myocardial infarction with a trigger event9 ; even though more recent studies of triggering using the case-crossover design mitigate such overreporting,34 an event influence, such as an episode of anger, may indeed involve more than one plaque. Lowering of oxidized lipoproteins reduces the likelihood of fissuring35 (what can hardly be conceived as a single plaque phenomenon). High catecholamine levels frequently participate in triggering infarction2 (by enhancing platelet activation and the generation of thrombin). Occurrence of reinfarction at a different site is enhanced in the early postinfarction phase36 (3 of our patients had worsening of nonoffending plaques leading to interim unstable rest angina7 37 38 ). "Active" coronary disease is associated with an increased level of an acute-phase reactant12 13 and monocyte activation39 (raising the intriguing question40 of whether these alterations reflect an exacerbation of an inflammatory response of single or of multiple arteries). The greater erythrocyte sedimentation rate that we observed at repeat angiography in patients with progression of the disease compared with those with steadiness or regression or with control subjects may be significant in this respect.
As a whole, 49% of nonculprit lesions appeared to be unsteady in the early postinfarction period; 38% showed progression as well as a tendency toward "complex" morphology and 11% showed regression and loss of complexity. In certain patients, however, the true culprit lesion cannot be identified, and if the lesions called "nonoffending" were indeed offending ones, increased progression would be expected. Although not excludable, this possibility is weakened by the fact that in 4 patients, two similarly severe narrowings in the same infarct-related vessel were classified as culprit. Another consideration is that 9 were not consecutive patients (angiography decision was made by the private physician), and the selection could have been biased toward more severe cases and might explain the greater changes in the infarction group. This bias, however, is probably not such as to significantly dilute results in the other 14 cases (consecutive patients aged <55 years).
How may our findings be interpreted according to the thesis of an exacerbation of coronary atherosclerotic activity, with multiple site involvement, coincident with acute infarction? It might be proposed that the rate of progress as a consequence of the destabilization process varies according to "maturation" stage in the life of an atheroma cycle. In most growing lesions, progression is probably rapid, and its maximal expression is at the level of the offending plaque; acute progression of nonoffending plaques persists or regresses according to the persistence of the inciting process, occurrence of shrinkage, mural thrombus lysis, or vascular remodeling. The fate of the culprit lesion is in part related to thrombus formation and effects of thrombolysis. In our patients the pattern of the infarct-related lesions was an early stabilization with some late tendency to further narrowing or occlusion.32 It is significant that worsening was shared by nonculprit lesions in the same patients.
Several crucial points remain obscure, mainly because of limitations of the angiographic method. What is the real proportion of the "activated" lesions, the time course of the exacerbation process mainly in relation with the acute event, the rate of "maturation" of a plaque toward rupture or thrombus formation, and the percentage of regression of the activated nonoffending lesions? Is there a waxing and a waning phase? Answers are hindered by two facts: (1) infarction is unpredictable and (2) coronary angiography in this particular setting is like a single frame in a dynamic process. Another limitation of the angiographic method is the inability to detect lesions that are "obscured" by coronary artery remodeling.3 41 This may help explain the lack of association of new narrowing development; another reason might be that young lesions are not involved in the exacerbation process underlying acute myocardial infarction.
Conclusions
Taken together, these results are consistent with the
hypothesis that acute infarction of the heart is a hallmark of a
systemic progression involving multiple coronary artery plaques
and is not purely a reflection of increased atherosclerotic activity in
a single plaque. Further angiographic studies as well as other imaging
techniques are needed to study the behavior of nonculprit
coronary plaques in patients with and without unstable
syndromes.
|
Acknowledgments |
|---|
This study was supported in part by a grant from the National Research Council, Rome, the Ministry of Health, Rome, the University of Milan, and the Monzino Foundation, Milan, Italy.
Received February 17, 1997; revision received March 4, 1997; accepted March 11, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363-373.
2.
Fuster V. Mechanisms leading to myocardial
infarction: insights from studies of vascular biology.
Circulation. 1994;90:2126-2146.
3.
Libby P. Molecular bases of the acute
coronary syndromes. Circulation. 1995;91:2844-2850.
4.
Hackett D, Davies G, Maseri A. Pre-existing
coronary stenoses in patients with first myocardial
infarction are not necessarily severe. Eur Heart
J. 1988;9:1317-1323.
5. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Mosen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56-62.[Abstract]
6. Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, Kim K, Shindo T, Kimura K. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol. 1991;18:904-915.[Abstract]
7. Forrester J. Intimal disruption and coronary thrombosis: its role in the pathogenesis of human coronary disease. Am J Cardiol. 1991;68:69B-77B.[Medline] [Order article via Infotrieve]
8.
Loree HM, Kamm RD, Stringfellow RG, Lee RT.
Effects of fibrous cap thickness on peak circumferential stress in
model atherosclerotic vessels. Circ Res. 1992;71:850-858.
9. Mac Isaac AI, Thomas J, Topol EJ. Toward the quiescent coronary plaque. J Am Coll Cardiol. 1993;22:1228-1241.[Abstract]
10.
Zeiher AM, Goebel H, Schächinger V, Ihling
C. Tissue endothelin-1 immunoreactivity in the active
atherosclerotic plaque: a clue to the mechanism of increased
vasoreactivity of the culprit lesion in unstable angina.
Circulation. 1995;91:941-947.
11. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801-809.[Medline] [Order article via Infotrieve]
12. Berk BC, Weintraub WS, Alexander W. Elevation of C-reactive protein in `active' coronary artery disease. Am J Cardiol. 1990;65:168-172.[Medline] [Order article via Infotrieve]
13.
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi
AG, Pepys MB, Maseri A. The prognostic value of C-reactive
protein and serum amyloid protein in severe unstable angina.
N Engl J Med. 1994;331:417-424.
14.
van der Wal AC, Becker AE, van der Loos CM, Das
PK. Site of intimal rupture or erosion of thrombosed
coronary atherosclerotic plaques is characterized by an
inflammatory process irrespective of the dominant plaque
morphology. Circulation. 1994;89:36-44.
15.
Buja LM, Willerson JT. Role of inflammation in
coronary plaque disruption. Circulation. 1994;89:503-505.
16.
Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V,
Fallon JT. Macrophage infiltration in acute
coronary syndromes: implications for plaque rupture.
Circulation. 1994;90:775-778.
17.
Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL,
Edwards PA, Watson AD, Lusis AJ.
Atherosclerosis: basic mechanisms: oxidation,
inflammation, and genetics. Circulation. 1995;91:2488-2496.
18. Rubin DB. Multivariate matching methods that are equal percent bias reducing, I: some examples. Biometrics. 1976:32:109-120.
19. Loaldi A, Polese A, Montorsi P, De Cesare N, Fabbiocchi F, Ravagnani P, Guazzi MD. Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression or coronary arterial narrowings in angina pectoris. Am J Cardiol. 1989;64:433-439.[Medline] [Order article via Infotrieve]
20. Lichtlen PR, Hygenholtz PG, Rafflenbeul W, Hecker H, Jost S, Deckers JW, on behalf of the INTACT Group Investigators. Retardation of angiographic progression of coronary artery disease by nifedipine: results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). Lancet. 1990;335:1109-1113.[Medline] [Order article via Infotrieve]
21.
Waters P, Lespérance J, Francetich M, Causey D,
Théroux P, Chiang YK, Hudon G, Lemarbre L, Retman M, Joyal M,
Gosselin G, Dyrda I, Macer J, Havel RJ. A controlled clinical
trial to assess the effect of a calcium channel blocker on the
progression of coronary
atherosclerosis. Circulation. 1990;82:1940-1953.
22. Lespérance J, Hudson G, White C, Laurier J, Waters D. Comparison by quantitative angiographic assessment of coronary stenoses of one view showing the severest narrowing to two orthogonal views. Am J Cardiol. 1989;64:462-465.[Medline] [Order article via Infotrieve]
23.
Falk E, Fuster V. Angina pectoris and disease
progression. Circulation. 1995;92:2033-2035.
24. Gibson CM, Sandor T, Stone PH, Pasternak RC, Rosner B, Sacks FM. Quantitative angiographic and statistical methods to assess serial changes in coronary luminal diameter and implications for atherosclerosis regression trials. Am J Cardiol. 1992;69:1286-1290.[Medline] [Order article via Infotrieve]
25.
Bogaty P, Brecker SJ, White SE, Stevenson RN, El-Tamini
H, Bacon R, Maseri A. Comparison of coronary
angiographic findings in acute and chronic first
presentation of ischemic heart disease.
Circulation. 1993;87:1938-1946.
26.
Kaski JC, Chester MR, Chen L, Katritsis D. Rapid
angiographic progression of coronary artery disease in patients
with angina pectoris: the role of complex stenosis
morphology. Circulation. 1995;92:2058-2065.
27. Moise A, Théroux P, Taeymans Y, Descoings B, Lespérance J, Waters D, Pelletier GB, Bourassa M. Unstable angina and progression of coronary atherosclerosis. N Engl J Med. 1983;309:685-689.[Abstract]
28. Kaski JC, Tousoulis D, Pereira WI, Crea F, Maseri A. Progression of complex coronary artery stenosis in patients with angina pectoris: its relation to clinical events. Coron Artery Dis. 1992;3:305-312.
29.
Bemis CE, Gorlin R, Kemp HG, Herman MV.
Progression of coronary artery disease: a clinical
arteriographic study. Circulation. 1973;47:455-464.
30.
Kramer JR, Matsuda Y, Mulligan JC, Aronow M, Proudfit
WL. Progression of coronary
atherosclerosis. Circulation. 1981;63:519-526.
31.
Chen L, Chester MR, Redwood S, Huang J, Leatham E,
Kaski JC. Angiographic stenosis progression and
coronary events in patients with `stabilized' unstable
angina. Circulation. 1995;91:2319-2324.
32. Davies SV, Marchant B, Lyons JP, Timmis AD, Rothman MT, Layton CA, Balcon R. Coronary lesion morphology in acute myocardial infarction: demonstration of early remodelling after streptokinase treatment. J Am Coll Cardiol. 1990;16:1079-1086.[Abstract]
33.
Falk E. Plaque rupture with severe pre-existing
stenosis precipitating coronary thrombosis:
characteristics of coronary atherosclerotic plaques underlying
fatal occlusive thrombi. Br Heart J. 1983;50:127-134.
34.
Mittleman MA, Maclure M, Sherwood JB, Mulry RP, Tofler
GH, Jacobs SC, Friedman R, Benson H, Muller JE; for the Determinants of
Myocardial Infarction Onset Study Investigators. Triggering of acute
myocardial infarction onset by episodes of anger.
Circulation. 1995;92:1720-1725.
35.
Brown BG, Zhao XQ, Sacco DE, Albers JJ. Lipid
lowering and plaque regression: new insights into prevention of plaque
disruption and clinical events in coronary disease.
Circulation. 1993;87:1781-1791.
36. Gilpin EA, Koziol JA, Madsen EB, Henning H, Ross J. Periods of differing mortality distribution during the first year after acute myocardial infarction. Am J Cardiol. 1983;52:240-244.[Medline] [Order article via Infotrieve]
37.
Willerson JT, Golino P, Eidt J, Campbell WB, Buja
LM. Specific platelet mediators and unstable
coronary artery lesions: experimental evidence and potential
clinical implications. Circulation. 1989;80:198-205.
38.
Braumwald E. Unstable angina: a
classification. Circulation. 1989;80:410-414.
39.
Alexander RW. Inflammation and coronary
artery disease. N Engl J Med. 1994;331:468-469.
40.
Neri Serneri GG, Abbate R, Gori M, Attanasio M, Martini
F, Giusti B, Dabizzi P, Poggesi L, Modesti PA, Trotta F, Rostagno C,
Boddi M, Gensini GF. Transient intermittent lymphocyte
activation is responsible for instability of angina.
Circulation. 1992;86:790-797.
41.
Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Potvin
Klein K. Remodelling of coronary arteries in human and
nonhuman primates. JAMA. 1994;271:289-294.
This article has been cited by other articles:
 |
|
 |
|
  L. M. Biasucci, M. Leo, and G. L. De Maria Local and Systemic Mechanisms of Plaque Rupture Angiology, August 1, 2008; 59(2_suppl): 73S - 76S. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Sdringola, C. Loghin, F. Boccalandro, and K. L. Gould Mechanisms of Progression and Regression of Coronary Artery Disease by PET Related to Treatment Intensity and Clinical Events at Long-Term Follow-up J. Nucl. Med., January 1, 2006; 47(1): 59 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rioufol, M. Gilard, G. Finet, I. Ginon, J. Boschat, and X. Andre-Fouet Evolution of Spontaneous Atherosclerotic Plaque Rupture With Medical Therapy: Long-Term Follow-Up With Intravascular Ultrasound Circulation, November 2, 2004; 110(18): 2875 - 2880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Haft, G. Rioufol, G. Finet, I. Ginon, X. Andre-Fouet, R. Rossi, E. Vialle, E. Desjoyaux, G. Convert, J.-F. Huret, et al. Multiple Atherosclerotic Plaque Rupture in Acute Coronary Syndrome * Response Circulation, March 11, 2003; 107 (9): e65 - e66. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 A. C. Sposito and M. J. Chapman Statin Therapy in Acute Coronary Syndromes: Mechanistic Insight Into Clinical Benefit Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1524 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rioufol, G. Finet, I. Ginon, X. Andre-Fouet, R. Rossi, E. Vialle, E. Desjoyaux, G. Convert, J.F. Huret, and A. Tabib Multiple Atherosclerotic Plaque Rupture in Acute Coronary Syndrome: A Three-Vessel Intravascular Ultrasound Study Circulation, August 13, 2002; 106(7): 804 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Goldstein Angiographic plaque complexity: the tip of the unstable plaque iceberg J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1464 - 1467. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Goldstein, D. Demetriou, C. L. Grines, M. Pica, M. Shoukfeh, and W. W. O'Neill Multiple Complex Coronary Plaques in Patients with Acute Myocardial Infarction N. Engl. J. Med., September 28, 2000; 343(13): 915 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schmermund, A. E. Denktas, J. A. Rumberger, T. F. Christian, P. F. Sheedy II, K. R. Bailey, and R. S. Schwartz Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease: Comparison with cardiac risk factors and radionuclide perfusion imaging J. Am. Coll. Cardiol., September 1, 1999; 34(3): 777 - 786. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||