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(Circulation. 1995;91:968-972.)
© 1995 American Heart Association, Inc.

Articles

Local Lesion-Related Factors and Restenosis After Coronary Angioplasty

Evidence From a Quantitative Angiographic Study in Patients With Unstable Angina Undergoing Double-Vessel Angioplasty

Pascal de Groote, MD; Christophe Bauters, MD; Eugène P. McFadden, MRCPI; Jean-Marc Lablanche, MD; Fabrice Leroy, MD; Michel E. Bertrand, MD

From the Service de Cardiologie B et Hémodynamique, Hôpital Cardiologique, Lille Cedex, France.

Correspondence to M.E. Bertrand, MD, Hôpital Cardiologique, Boulevard du Professeur J Leclercq, 59037 Lille Cedex, France.

	Abstract

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Background Restenosis rates are high when coronary angioplasty is performed in patients with unstable angina. The relative contributions of local and systemic factors to this excess risk of restenosis are unclear. To assess these, we compared changes in minimal lumen diameter and the incidence of restenosis, determined by quantitative coronary angiography, after coronary angioplasty at culprit and nonculprit lesions dilated in the course of a single procedure in patients with unstable angina.

Methods and Results We identified 67 consecutive patients with unstable angina in whom two lesions, in different vessels, were dilated during the same procedure. Lesions were designated as culprit or nonculprit on the basis of the location of ECG changes during chest pain combined with assessment of the angiographic characteristics of the lesions. With these criteria, 43 patients had identifiable culprit lesions. Stenosis severity before and immediately after angioplasty and at follow-up was assessed with quantitative angiography. Angiographic follow-up was performed in 91% (39 patients) of this subgroup. Culprit lesions were more severe (P<.02) than nonculprit lesions. The late loss at culprit lesions (0.87±0.75 mm) was significantly (P<.01) greater than the equivalent value for nonculprit lesions (0.33±0.69 mm). With a categorical definition (>50% stenosis at follow-up), restenosis occurred at 67% of culprit lesions and at 32% of nonculprit lesions (P<.01).

Conclusions The greater loss in minimal lumen diameter and the consequent higher rate of restenosis at culprit compared with nonculprit lesions suggest that local "lesion-related" factors are an important determinant of the high rate of restenosis when coronary angioplasty is performed in patients with unstable angina.

Key Words: restenosis • vessels • angiography • angina

	Introduction

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Several studies have documented very high rates of restenosis when percutaneous transluminal coronary angioplasty (PTCA) is performed in patients with unstable angina.^{1 2} The consistent association between "unstable angina" and an increased risk of restenosis is particularly remarkable as the definition of unstable angina varies widely among studies; some authors included patients with recent-onset angina or a deterioration in preexisting stable angina, whereas others required the demonstration of transient ECG changes during pain.^{3 4}

The mechanisms of this increased predisposition to restenosis in unstable angina remain unclear. Lesions with specific morphological features, such as the presence of thrombus, that have themselves been associated with an increased risk of restenosis are more common in patients with unstable angina.^{5 6} However, metabolic studies demonstrate an increase in systemic platelet aggregability and a decrease in fibrinolytic activity in patients with unstable angina that could also contribute to the enhanced risk of restenosis.^{7 8}

If these systemic alterations play a dominant role in the increased predisposition to restenosis in the setting of unstable angina, one would expect an increase in the restenosis rate of nonculprit lesions when they are dilated at the same time as culprit lesions in such patients. Accordingly, we identified a group of patients with unstable angina with a clearly identified culprit lesion who underwent successful double-vessel angioplasty during a single catheterization session. We compared, using quantitative angiography, the changes in minimal lumen diameter between angioplasty and follow-up and the incidence of restenosis, defined as a categorical variable, at culprit and nonculprit lesions.

	Methods

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Patients
We studied 67 consecutive patients with unstable angina (as defined below) who between 1987 and 1993 underwent successful PTCA of two lesions in different vessels during the same catheterization session. Patients with a recent (within 3 months) myocardial infarction were excluded.

Unstable angina was defined as recurrent episodes of angina at rest associated with reversible significant (1-mm) ST-segment shift or transient symmetrical T-wave inversion or giant negative T-waves in the anterior leads but without enzymatic evidence of myocardial necrosis occurring in patients with preexisting stable angina or with new-onset (within 1 month) angina. All patients continued to experience daily episodes of chest pain with associated ECG changes while receiving medical therapy of combinations of ß-adrenergic receptor antagonists, intravenous nitrates, and calcium antagonists. All were receiving 100 to 300 mg/d aspirin.

Identification of Culprit Lesion
Two observers who were unaware of the angiographic findings independently analyzed a 12-lead ECG recorded during an episode of angina and a baseline ECG from each patient. They documented the ECG leads in which significant ECG changes (defined as above) occurred. We postulated, as suggested by previous authors, that the territory of the left anterior descending coronary artery was the site of the culprit lesion when ECG changes occurred in leads V₂ through V₄ or V₂ through V₆.^{9 10} The territory of the left circumflex coronary artery was presumed to be the site of the culprit lesion if ECG changes occurred in leads I and aVL and/or V₅ and V₆. The territory of the right coronary artery was presumed to be the site of the culprit lesion if ECG changes occurred in leads II, III, and aVF. Using these criteria, the two observers agreed independently on the designation of the culprit territory in 44 patients.

Two other observers who were unaware of the ECG findings independently reviewed the coronary angiograms of the 44 patients in whom the culprit lesion was identifiable by the ECG findings. They classified the coronary circulation as right dominant, left dominant, or indeterminate and classified the left anterior descending coronary artery as type I, II, or III as a function of the extent of myocardium supplied by that artery using the classification proposed by Effler.¹¹ They performed a qualitative analysis of the morphology of the lesions to determine the presence or absence of lesion characteristics that are known to be associated with instability, ie, the presence of thrombus, overhanging edges, ulceration, and irregularity.¹² They subsequently divided the patients into two groups–patients in whom, on the basis of angiographic characteristics, one lesion could clearly be designated as a culprit lesion and the other as a nonculprit, and patients in whom the angiographic characteristics did not permit the designation of a culprit lesion.

The ECG classification and the angiographic classification were combined. In 35 patients, the lesion designated as culprit by ECG criteria was also classified as the culprit lesion by angiographic criteria. In 1 patient, the ECG and angiographic classification were discordant. This patient was excluded. In the remaining 8 patients, a culprit lesion was identified by ECG criteria, whereas no definite culprit lesion could be designated by the angiographic criteria. Thus, 43 patients had an identifiable culprit lesion by ECG criteria that was compatible with the angiographic findings; the 39 patients (91%) who underwent angiographic follow-up make up the study population.

Angioplasty Procedure
PTCA was performed using the standard technique in our institution. At the start of the procedure, all patients were administered heparin (10 000 IU IV) and isosorbide dinitrate (1 to 2 mg IC). In our institution, angiography is routinely performed in two projections before and immediately after angioplasty. These projections are recorded and used in the follow-up study that is recommended to all patients at 6 months after angioplasty. Angiography is performed earlier if there is a clinical indication.

Coronary angioplasty was considered successful when the residual luminal narrowing in the dilated segment, immediately after coronary angioplasty, was visually estimated as <50% and when no major complication (ECG or enzymatic evidence of myocardial infarction, the need for bypass surgery during hospitalization, or in-hospital death) occurred. Restenosis was defined as a categorical variable, ie, the recurrence of >50% luminal narrowing, in a segment that had been previously dilated to <50%.

Angiographic Analysis
Quantitative computer-assisted angiographic measurements were performed with use of the Computer-Assisted Evaluation of Stenosis and Restenosis (CAESAR) system. The accuracy and reproducibility of measurements obtained using this system, under routine clinical conditions, have been previously reported.¹³ The quantitative measurements were performed on end-diastolic frames from these angiograms by one investigator who was unaware of the design of the study. The reference diameter and the minimal lumen diameter at the dilated site before, immediately after, and at follow-up angiography were measured at each lesion. From these measurements we derived the acute gain (minimal lumen diameter immediately after PTCA minus minimal lumen diameter before PTCA), the late loss (minimal lumen diameter immediately after PTCA minus minimal lumen diameter at follow-up angiography), and the loss index (the average ratio of late loss to acute gain) for culprit and for nonculprit lesions.¹⁴

Statistical Analysis
Values are given as mean±SD. Characteristics associated with culprit and nonculprit lesions were compared with use of paired Student's t tests for continuous variables and of ² analysis for categorical variables.

	Results

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Thirty-nine patients (91%) underwent angiographic follow-up. The remaining 4 patients did not undergo angiographic follow-up for the following reasons: 1 patient refused, 1 patient had emigrated, and 2 were >80 years old and were asymptomatic. The baseline characteristics of the patients who had successful PTCA and who underwent follow-up angiography (n=39) are summarized in Table 1. There was a high prevalence of risk factors for coronary disease. Forty-eight percent of patients had triple-vessel disease.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics for Study Population

The location of the dilated lesions and the procedural variables are presented in Table 2. There was a greater proportion of left anterior descending coronary artery lesions in the culprit lesion group. Angiographic evidence of thrombus was found only at culprit lesions (n=6). The perfusion grade, defined as in the Thrombolysis in Myocardial Infarction trial, was significantly (P<.02) less at culprit (2.51±0.91 mm) than at nonculprit (2.9±0.3 mm) lesions.

View this table: [in this window] [in a new window]   Table 2. Lesion Characteristics and Procedural Variables for Study Population

The quantitative angiographic data are presented in Table 3. Before angioplasty, mean percentage stenosis severity was significantly greater and absolute minimal lumen diameter significantly less at culprit lesions. Just after angioplasty, mean percent residual stenosis and mean minimal lumen diameter were similar for both types of lesion. Thus, the acute gain in lumen diameter associated with angioplasty was significantly greater at culprit lesions.

View this table: [in this window] [in a new window]   Table 3. Quantitative Angiographic Data for Study Population

The late loss (P<.01) and the loss index (P=.01) were significantly greater at culprit than at nonculprit lesions. With a categorical definition of restenosis (>50% stenosis at follow-up by quantitative angiography), the restenosis rate at culprit lesions (67%) was significantly (P<.01) higher than at nonculprit lesions (32%); in 9 patients (23%), restenosis occurred at both lesions, and in 9 patients (23%), neither lesion restenosed. Total occlusion at follow-up was present at 4 culprit lesions (10.3%) but at no nonculprit lesion. When the values for loss in minimal lumen diameter between PTCA and follow-up were recalculated after exclusion of these lesions, the late loss in minimal lumen diameter was also significantly (P<.05) greater at culprit (0.71±0.65 mm) than at nonculprit (0.38±0.96 mm) lesions. The loss index at culprit lesions (0.65±0.57 mm) remained significantly (P<.03) greater than at nonculprit lesions (0.30±0.74 mm).

With the categorical definition of restenosis, the overall restenosis rate was 31.2% in the circumflex artery, 50% in the right coronary artery, and 59.4% in the left anterior descending coronary artery.

	Discussion

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The major finding of the present study was that when culprit and nonculprit lesions were dilated during the same procedure in patients with unstable angina, the absolute decrease in minimal lumen diameter between angioplasty and follow-up angiography was more than twice as great at culprit lesions as at nonculprit lesions. In addition, restenosis, assessed with a categorical definition, occurred twice as frequently at culprit lesions (67%) than at nonculprit lesions (32%). These observations are consistent with the hypothesis that the increased rate of restenosis in patients with unstable angina predominantly reflects the influence of local lesion-related factors.

Local Factors and Restenosis
The frequent occurrence of clinically important restenosis is one of the major limitations of angioplasty in the treatment of atheromatous coronary disease. The mechanisms of restenosis are incompletely understood, but restenosis appears to be an exaggeration of a natural healing response after arterial injury. Numerous experimental observations suggest that local factors play a major role in the pathophysiology of restenosis. Angioplasty is invariably associated with arterial injury that provides a potent stimulus for both platelet adhesion and platelet aggregation. Platelet aggregation at the angioplasty site may contribute to restenosis by releasing substances that stimulate smooth muscle cell migration and proliferation.¹⁵ This hypothesis is supported by the observation that the degree of intimal thickening that occurs after experimental balloon injury is markedly less in animals with thrombocytopenia than in control animals.¹⁶ However, several clinical studies have failed to demonstrate a beneficial effect of antiplatelet agents, such as aspirin or GR32191B (a thromboxane A₂ receptor antagonist), on the occurrence of restenosis after angioplasty in humans.^{17 18}

In the present study, the rate of restenosis at nonculprit lesions was similar to that reported, using the same definition, in a recent large study of the effects of GR32191B on restenosis.¹⁹ Furthermore, the change in minimal lumen diameter between angioplasty and follow-up at nonculprit lesions (0.33±0.69 mm) was comparable to that observed in control patients in two recent studies on restenosis prevention with GR32191B (0.31±0.54 mm) and with cilazapril (0.29±0.49 mm) that included predominantly patients with stable angina.^{18 20} It appears, therefore, that the existence of a systemic increase in platelet activation, which has been documented in comparable patients with unstable angina, does not have an important effect on the restenotic process.⁷ However, this is not incompatible with a role for platelets in either the excess risk of restenosis at culprit lesions or in the pathophysiology of restenosis in general. The systemic increase in platelet activation in unstable angina is undoubtedly related to intense local platelet activation at the culprit lesion. The failure of antiplatelet agents to affect the rate of restenosis in clinical studies may reflect the fact that these agents predominantly affect platelet aggregation rather than platelet adhesion. Experimental studies suggest that the platelet-derived substances that contribute to the restenotic process predominantly originate from the monolayer of platelets that adhere at the angioplasty site.²¹ Furthermore, other platelet-independent stimuli can also stimulate smooth muscle cell proliferation and migration.²² Recent studies have suggested that a local inflammatory response may play a role in the pathogenesis of unstable angina. Granulocyte and monocyte activations have been shown to occur in the coronary circulation in unstable angina, and these cells secrete substances that may further stimulate smooth muscle cell proliferation.^{22 23} High local concentrations of such substances at culprit but not nonculprit lesions might in part explain the observed disparity in restenosis rates.

Role of Angiographic Lesion Morphology
We found that the morphological characteristics of the culprit lesions were more complex than those of the nonculprit lesions. Several studies suggested that specific lesion characteristics such as eccentricity, length, and the presence of thrombus were associated with an increased risk of restenosis.^{24 25} However, other studies did not support these conclusions, suggesting that, if it exists, an effect of morphological characteristics on restenosis is weak.²⁶ The conflicting results of these studies may be related to the documented limitations of angiography in the assessment of lesion morphology: newer techniques such as angioscopy and intravascular ultrasound imaging that allow a more precise assessment of lesion morphology may help to resolve this question.

Potential Mechanisms of Enhanced Culprit Lesion Restenosis
A growing body of evidence suggests that the natural evolution of atherosclerotic plaques in humans is closely related to spontaneous episodes of plaque rupture causing a local response that has features in common with that seen after the iatrogenic injury of coronary angioplasty.²⁷ In both cases, platelet aggregation at the site of injury, whether spontaneous or iatrogenic, leads to the release of vasoconstrictor and mitogenic substances that may provoke smooth muscle cell proliferation. Unstable lesions and restenotic lesions share common histopathological features. Histological studies have revealed evidence of a comparable degree of smooth muscle cell proliferation in tissue retrieved during directional atherectomy procedures performed in patients with unstable angina and in patients with restenosis.²⁸ The presence of proliferating smooth muscle cells in both types of lesion may be related in a fundamental way to the high rates of restenosis observed when angioplasty is performed in these apparently different patient populations. Experimental studies have shown that when repeat balloon injury is performed early after an initial injury, the degree of smooth muscle cell proliferation is greater than that observed if a greater time interval has elapsed since the first injury.²⁹ We have recently shown that a similar phenomenon occurs in humans. The rate of restenosis when a repeat angioplasty was performed within 3 months of a first procedure was markedly greater than that observed when the second procedure was undertaken later. Furthermore, in patients who underwent early repeat dilation, the same elevated risk of restenosis was seen whether they had stable or unstable symptoms.³⁰ It has also been shown that angioplasty in patients with unstable angina is associated with a better immediate outcome when the angioplasty procedure is performed after a period of medical treatment than when it is performed soon after the onset of unstable angina.³¹ However, it is not clear whether a delayed angioplasty is associated with a diminution in the rate of restenosis. It is plausible that the increased rates of restenosis that are observed when angioplasty is performed at "active" lesions, ie, at culprit lesions in patients with unstable angina or at lesions that undergo restenosis early after a previous dilation, may be related to a synergistic effect of mechanical stimulation on already proliferating smooth muscle cells. Alternatively, it is possible that the increased rates of restenosis reflect selection for patients with aggressive proliferation. An additional factor that may be involved in the late loss in lumen diameter after angioplasty is elastic recoil and late vascular remodeling.³² The design of the present study did not allow us to assess its potential role in the observed difference in late angiographic outcome between culprit and nonculprit lesions. Finally, the higher rate of restenosis observed at culprit lesions may, in part, be a reflection of the greater proportion of left anterior descending lesions in this group. The overall rate of restenosis was highest at left anterior descending lesions, as previously demonstrated by Kuntz et al.³³

Potential Limitations
Unstable angina defined by the strict criteria that we used is uncommon. This fact combined with the necessity to exclude patients without a clearly identifiable culprit lesion explains the relatively small number of patients. Moreover, as in most institutions, we generally dilate only the presumed culprit lesion in such patients. The retrospective design of our study does not allow us to determine why, in this small group of patients, a double procedure was performed. Finally, the fact that a greater proportion of culprit lesions were located in the left anterior descending coronary artery should not be taken to imply that unstable angina is more frequently due to lesions in that vessel; it is more likely to be a consequence of the use of ECG changes to identify culprit lesions as the 12-lead ECG has a greater sensitivity for the detection of anterior ischemia.

Conclusions
Our results, which document a high rate of restenosis at culprit but not at nonculprit lesions dilated at the same time, suggest that local "lesion-related" factors are an important determinant of the excess risk of restenosis when coronary angioplasty is performed in patients with unstable angina.

Received June 20, 1994; revision received August 30, 1994; accepted September 23, 1994.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Leimgruber PP, Roubin GS, Hollman J, Cotsonis GA, Meier B, Douglas JS, King SB III, Gruentzig AR. Restenosis after successful coronary angioplasty in patients with single-vessel disease. Circulation. 1986;73:710-717. [Abstract/Free Full Text]
   
2. Plokker HWT, Ernst SMPG, Bal ET, van den Berg ECJM, Mast GEG, van der Feltz TA, Ascoop CAPL. Percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris refractory to medical therapy: long-term clinical and angiographic results. Cathet Cardiovasc Diagn. 1988;14:15-18. [Medline] [Order article via Infotrieve]
   
3. Steffenino G, Meier B, Finci L, Rutishauser W. Follow-up results of treatment of unstable angina by coronary angioplasty. Br Heart J. 1987;57:416-419. [Abstract/Free Full Text]
   
4. de Feyter PJ, Serruys PW, van den Brand M, Soward A. Coronary angioplasty for treatment of unstable angina with transient marked ST-segment elevation. Eur Heart J. 1987;8:569-574. [Abstract/Free Full Text]
   
5. Ambrose JA, Winters SL, Stern A, Eng A, Teichholz LE, Gorlin R, Fuster V. Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol. 1985;5:609-616. [Abstract]
   
6. Halon DA, Merdler A, Shefer A, Flugelman MY, Lewis BS. Identifying patients at high risk for restenosis after percutaneous transluminal coronary angioplasty for unstable angina pectoris. Am J Cardiol. 1989;64:289-293. [Medline] [Order article via Infotrieve]
   
7. Fitzgerald DJ, Rov L, Catella F, Fitzgerald GA. Platelet activation in unstable coronary disease. N Engl J Med. 1986;315:983-989. [Abstract]
   
8. Zalewski A, Shi Y, Nardone D, Bravette B, Weinstock P, Fischman D, Wilson P, Goldberg S, Levin DC, Bjornsson TD. Evidence of reduced fibrinolytic activity in unstable angina at rest: clinical, biochemical, and angiographic correlates. Circulation. 1991;83:1685-1691. [Abstract/Free Full Text]
   
9. de Feyter PJ, Suryapranata H, Serruys PW, Beatt K, van Domburg R, van den Brand M, Tijssen JJ, Azar AJ, Hugenholtz PG. Coronary angioplasty for unstable angina: immediate and late results in 200 consecutive patients with identification of risk factors for unfavorable early and late outcome. J Am Coll Cardiol. 1988;12:324-333. [Abstract]
   
10. Wohlgelernter D, Cleman M, Highman HA, Zaret BL. Percutaneous transluminal coronary angioplasty of the `culprit lesion' for management of unstable angina pectoris in patients with multivessel coronary artery disease. Am J Cardiol. 1986;58:460-464. [Medline] [Order article via Infotrieve]
    
11. Gensini GG. Coronary arteriography. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 2nd ed. Philadelphia, Pa: WB Saunders; 1984:304-350.
    
12. Ambrose JA, Israel DH. Angiography in unstable angina. Am J Cardiol. 1991;68:78B-84B. [Medline] [Order article via Infotrieve]
    
13. Bertrand ME, Lablanche JM, Bauters C, Leroy F, MacFadden E. Discordant results of visual and quantitative estimates of stenosis severity before and after coronary angioplasty. Cathet Cardiovasc Diagn. 1993;28:1-6. [Medline] [Order article via Infotrieve]
    
14. Kuntz RE, Baim DS. Defining coronary restenosis: newer clinical and angiographic paradigms. Circulation. 1993;88:1310-1323. [Free Full Text]
    
15. Fingerle J, Johnson R, Clowes AW, Majesky MW, Reidy MA. Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci U S A. 1989;86:8412-8416. [Abstract/Free Full Text]
    
16. Friedman RJ, Stemermam MB, Wenz B, Moore S, Gauldie J, Gent M, Tiell ML, Spaet TH. The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. J Clin Invest. 1977;60:1191-1201.
    
17. Schwartz L, Bourassa MG, Lesperance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med. 1988;318:1714-1719. [Abstract]
    
18. Serruys PW, Rutsch W, Heyndrickx GR, Danchin N, Mast EG, Wijns W, Rensing BJ, Vos J, Stibbe J, for the Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study Group (CARPORT). Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A₂–receptor blockade: a randomized, double-blind, placebo-controlled trial. Circulation. 1991;84:1568-1580. [Abstract/Free Full Text]
    
19. Rensing BJ, Hermans WR, Vos J, Beatt KJ, Bossuyt P, Rutsch W, Serruys PW, on behalf of the CARPORT Study Group. Quantitative angiographic risk factors of luminal narrowing after coronary balloon angioplasty using balloon measurements to reflect stretch and elastic recoil at the dilatation site. Am J Cardiol. 1992; 69:584-591.
    
20. The Multicenter European Research Trial With Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis. Does the new angiotensin converting inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Circulation. 1992;86:100-110. [Abstract/Free Full Text]
    
21. Liu MW, Roubin GS, King SB. Restenosis after coronary angioplasty: potential biologic determinants and role of intimal hyperplasia. Circulation. 1989;79:1374-1387. [Abstract/Free Full Text]
    
22. Neri Serneri GG, Abbate R, Gori AM, Attanasio M, Martini F, Giusti B, et al. Transient intermittent lymphocyte activation is responsible for the instability of angina. Circulation. 1992;86:790-797. [Abstract/Free Full Text]
    
23. Jude B, Agraou B, McFadden EP, Susen S, Bauters C, Lepelley P, Vanhaesbroucke C, Devos P, Cosson A, Asseman P. Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. Circulation. In press.
    
24. Hirshfeld JW, Schwartz SJ, Jugo R, MacDonald RG, Goldberg S, Savage MP, Bass TA, Vetrovec G, Cowley M, Taussig AS, Whitworth HB, Margolis JR, Hill JA, Pepine CJ, and the M-Heart Investigators. Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. J Am Coll Cardiol. 1991;18:647-656. [Abstract]
    
25. Bourassa MG, Lespérance J, Eastwood C, Schwartz L, Cote G, Kazim F, Hudon G. Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1991;18:368-376. [Abstract]
    
26. Ellis SG, Roubin GS, King SB, Douglas JS Jr, Cox WR. Importance of stenosis morphology in the estimation of restenosis risk after elective percutaneous transluminal coronary angioplasty. Am J Cardiol. 1989;63:30-34. [Medline] [Order article via Infotrieve]
    
27. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:242-250. [Medline] [Order article via Infotrieve]
    
28. Flugelman MY, Virmani R, Correa R, Yu ZX, Farb A, Leon MB, Elami A, Fu YM, Casscells W, Epstein SE. Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina: a clue to the mechanism of transformation from the stable to the unstable clinical state. Circulation. 1993;88:2493-2500. [Abstract/Free Full Text]
    
29. Schneider JE, Santoian EC, Gravanis MB, Cipolla GD, Tarazona N, Scott NA, King SB. Timing of repeat balloon injury influences intimal hyperplasia in a swine model of coronary restenosis. In: Topol EJ, ed. Proceedings of Restenosis Summit IV. Cleveland, Ohio: 1992:21. Abstract.
    
30. Bauters C, Lablanche JM, McFadden EP, Leroy F, Bertrand ME. Clinical characteristics and angiographic follow-up of patients undergoing early or late repeat dilation for a first restenosis. J Am Coll Cardiol. 1992;20:845-848. [Abstract]
    
31. Myler RK, Shaw RE, Sterzler SH, Bashour TT, Ryan C, Hecht HS, Cumberland DC. Unstable angina and coronary angioplasty. Circulation. 1990;82(suppl II):II-88-II-95.
    
32. Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431-1438. [Free Full Text]
    
33. Kuntz RE, Hinohara T, Robertson GC, Safian RD, Simpson JB, Baim DS. Influence of vessel selection on the observed restenosis rate after endoluminal stenting or directional atherectomy. Am J Cardiol. 1992;70:1101-1108.[Medline] [Order article via Infotrieve]
    

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