Carotid Endarterectomy in Patients 55 Years of Age and Younger

Carotid Endarterectomy in Patients 55 Years of Age and Younger Caron B. Rockman, MD, Jennifer K. Svahn, MD, David J. Willis, MD, Patrick J. Lamparello, MD, Mark A. Adelman, MD, Glenn R. Jacobowitz, MD, Andy M. Lee, MD, Paul Gagne, MD, Evan Deutsch, MD, Ronnie Landis, RN, and Thomas S. Riles, MD, New York, New York

Prior studies have suggested that young patients may be more prone to recurrent disease after carotid endarterectomy (CEA). The goal of this study was to review a series of CEAs performed on younger patients (ⱕ 55 years) and to determine if these patients are more likely to develop recurrent stenosis. A review was conducted of CEAs performed from 1985 through 1994. Analysis was performed on a study group of 94 young patients who underwent 109 CEAs during this time. A control group of 222 patients older than 55 years who underwent 256 CEAs during the years 1991 through 1993 was selected for comparison. During a mean of nearly 4 years of follow-up, younger patients were significantly more likely to experience a late failure of CEA, including total occlusion of the operated artery, or recurrent stenosis requiring redo surgery. Careful patient evaluation is important in choosing younger patients who require CEA. Implications of these data include mandating careful noninvasive follow-up examinations for younger patients undergoing CEA.

INTRODUCTION Carotid endarterectomy (CEA) is usually performed on elderly patients. It is unusual to perform surgery for carotid artery stenosis in patients younger than 55 years of age. Furthermore, previous studies have suggested that patients who develop recurrent carotid stenosis after prior endarterectomy are often significantly younger than those who do not. It has been shown that patients with early manifestations of carotid bifurcation disease may be more prone to late complications despite surgical intervention. Division of Vascular Surgery, New York University Medical Center, New York, NY. Presented as a poster at the Annual Meeting of the Society for Clinical Vascular Surgery, Rancho Mirage, CA, March 15, 2000. Correspondence to: C.B. Rockman, MD, New York University Medical Center, 530 First Avenue, Suite 6F, New York, NY 10016, USA, E-mail: [email protected]. Ann Vasc Surg 2001; 15: 557-562 DOI: 10.1007/s10016-001-0029-4 © Annals of Vascular Surgery Inc. Published online: August 23, 2001

With these issues in mind, the goal of this study was to review a series of CEAs performed on younger adults, to determine if these patients are more likely to develop recurrent carotid stenosis, to identify risk factors in younger patients who develop recurrent lesions, to assess the mechanisms of failure of the primary operations, and to establish an appropriate postoperative monitoring program in young patients.

PATIENTS AND METHODS A retrospective review was performed on a prospectively compiled database of all extracranial cerebrovascular surgery performed at the New York University Medical Center. All primary CEAs performed during the years 1985 through 1994 on patients aged 55 years or less were selected as a study group. This comprised 94 patients who underwent a total of 109 operations. Several patients who had their primary CEA elsewhere, or outside of the study dates, and had a redo operation per557

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formed at our institution during the study period were excluded from analysis. Data on demographics, preoperative characteristics, and intraoperative and perioperative courses and complications were available on all patients. A control group of 222 patients greater than 55 years of age undergoing 256 primary CEAs during the years 1991 through 1993 was selected for comparison. This particular group was selected for comparison because it was a similar number of concurrently treated patients in whom long-term follow-up was being prospectively collected for a research project regarding material used for patch angioplasty. Standard technique for CEA at our institution includes a preference for regional anesthesia with selective shunting, routine shunting for those cases performed under general anesthesia, and patch angioplasty closure for all cases, using either Dacron or veiny. Patients were defined as having specific atherosclerotic risk factors on the basis of patient medical history and medication regimen. Patients were defined as having hypertension on the basis of patient history, or if they were being treated with antihypertensives. Patients were defined as having cardiac disease if they reported being told of or being treated for coronary artery disease, valvular heart disease, congestive heart failure, or significant cardiac arrhythmias. Unfortunately, not enough of the patients had specific information on lipid profiles to allow for meaningful analysis. Follow-up duplex scans were obtained at varying intervals. Late failure of CEA was defined as occlusion of the operated artery, symptomatic restenosis, or significant asymptomatic restenosis requiring reoperation or other intervention. Statistical analysis was performed using the computer package SPSS (SPSS, Inc., Chicago, IL). Comparison of proportional variables was performed using the Pearson’s ␹2 test or the Fisher’s exact test where appropriate. Comparison of continuous variables was performed using the Student’s t-test. Results were considered significant with a p value < 0.05.

RESULTS Patient Demographics Young patients were significantly more likely to have a positive history of cigarette smoking than older patients (67.8% vs. 45.0%, p < 0.001). There were no significant differences between young and older patients with regard to gender or the presence of hypertension, diabetes, or cardiac disease (Table I).

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Table I. Comparison of patient demographics between younger and older patients

Gender (male) Hypertension Diabetes Smoking Cardiac disease

≤55 years [(n = 94) %]

>55 years [(n = 222) %]

p

62.8 52.7 27.5 67.8 46.8

56.3 62.2 19.4 45.0 45.9

NS NS NS <0.001 NS

NS, not significant.

Preoperative Symptoms and Indications for Surgery Young patients were significantly more likely than older patients to have sustained a preoperative stroke (29.4% vs. 17.2%, p = 0.02). There were no significant differences in the proportions of patients who were asymptomatic preoperatively or who had contralateral carotid occlusion. Overall, the indications for surgery differed significantly between younger and older patients (p = 0.04) (Table II). Intraoperative Course and Complications Young patients were significantly more likely to tolerate clamping of the carotid artery under regional anesthesia than were older patients (95.1% vs. 80.2%, p = 0.002). There were no significant differences in the rate of perioperative complications, including stroke, myocardial infarction, and death, between young and older patients (Table II). Follow-up Mean follow-up overall, including clinical followup alone, was 43.1 months (range 1-139.6 months). For patients under 55 years, mean clinical follow-up was 48.1 months, while for older patients it was 41.2 months. Follow-up duplex scans were obtained in 79.8% of younger patients and 85.8% of older patients. For patients with duplex followup only, the mean length of follow-up was 48.1 months for younger patients and 43.4 months for older patients. There were no significant differences in the lengths of follow-up or the percentage of patients undergoing follow-up duplex scans between the two patient groups. Late Failures Among younger patients, there were 10 late failures. These consisted of four total occlusions and six

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Table II. Comparison of preoperative and intraoperative characteristics and early outcome between younger and older patients

Indications for surgery TIA CVA Asymptomatic Contralateral occlusion Perioperative course Regional anesthesia Tolerated clamping Shunt used Perioperative MI Perioperative CVA Perioperative death

≤55 years (%)

>55 years (%)

p

45.0 29.4 25.7 14.3

54.3 17.2 28.5 14.2

NS 0.02 NS NS

78.0 95.1 29.6 0.9 1.8 0.9

77.7 80.2 40.2 0.8 1.6 1.6

NS 0.002 0.064 NS NS NS

冧

0.04

CVA, cerebrovascular accident; NS, not significant; TIA, transient ischemic attack.

restenoses requiring reoperation. The six reoperations encompassed three early restenoses secondary to neointimal hyperplasia and three late restenoses representing recurrent atherosclerosis. Among older patients there were six late failures. These consisted of three total occlusions and three restenoses requiring reoperation. The three restenoses in older patients all were secondary to early neointimal hyperplasia. There were no cases of late ipsilateral stroke without either total occlusion of the operated artery or significant restenosis. Of the total of 16 patients who experienced occlusion or severe restenosis of the artery, 13 (81.3%) had at least one interval duplex scan demonstrating patency of the operated artery. Further details regarding the patients who experienced a late failure are provided in Table III. Younger patients were significantly more likely to experience a late complication than older patients (11.5% vs. 2.8%, p = 0.008, Fisher’s exact test). Younger patients were significantly more likely to experience recurrent stenoses requiring redo surgery (6.9% vs. 1.4%, p = 0.02, Fisher’s exact test) (Table IV). Analysis revealed that among young patients, no specific demographic factor predicted the occurrence of either late occlusion or recurrent stenosis, including age, gender, smoking history, or the presence of diabetes, hypertension, or coronary artery disease. Since nearly all patients underwent patch angioplasty at the original operation, the effect of patching on recurrent stenosis could not be evaluated. The type of patch material did not appear to affect the rates of recurrent stenosis or occlusion. The per-

centages of patches used and their corresponding rates of restenosis or occlusion were 88 vein patches (83.8%), with a restenosis or occlusion rate of 9.1%; 2, polytetrafluoroethylene (PTFE) patches (1.9%), with a restenosis or occlusion rate of 50%; and 15 Dacron patches (14.3%), with a restenosis rate of 0%. One patient underwent primary closure, and this patient was one of those who experienced occlusion of the artery (100%). However, none of these numbers were statistically significant. The use of a shunt during the original operation did not have an affect on the rate of subsequent restenosis or occlusion (12.1% in the shunted group vs. 7.5% in the non-shunted group, p = NS).

DISCUSSION The prevalence of atherosclerosis clearly increases with advancing age. Because atherosclerosis is perceived as a disease of the older population, signs and symptoms of atherosclerosis in younger patients may be overlooked. However, premature atherosclerosis in younger patients may be even more virulent than in older patients, and is important to diagnose and investigate. Premature symptomatic atherosclerosis in areas other than the cerebrovascular circulation has been extensively studied. McCready et al.1 noted the striking development between the premature development of atherosclerotic cardiovascular disease and cigarette smoking. Valentine et al.2 studied patients less than 40 years of age with intermittent claudication and noted that symptomatic atherosclerosis in young patients implies a limited life expectancy. Levy et al.3 studied patients less than 40

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Table III. Details of late recurrent stenoses or occlusions

Patient

Age (years)

Restenosis or occlusion

Time to late failure

Intervening duplex scans?

Symptoms at time of diagnosis to late failure

Outcome

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

<55 <55 <55 <55 >55 <55 <55 <55 <55 <55 >55 >55 >55 >55 >55 >55

Restenosis Restenosis Restenosis Restenosis Restenosis Restenosis Occlusion Occlusion Occlusion Occlusion Restenosis Restenosis Restenosis Occlusion Occlusion Occlusion

6 1 3 6 6 7 6 6 6 8 1 1 3 9 1 3

Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes No No Yes

TIA None None TIA TIA None None Unknown CVA None None None TIA None None None

Redo surgery Redo surgery Redo surgery Redo surgery Redo surgery Redo surgery No intervention No intervention No intervention No intervention Redo surgery Redo surgery Redo surgery No intervention No intervention No intervention

months year years years years years months years years years year year years months year years

CVA, cerebrovascular accident; TIA, transient ischemic attack.

Table IV. Comparison of late outcome between younger and older patients

Total occlusion Restenosis Any late failure

≤55 years (%)

>55 years (%)

p

4.6 6.9 11.5

1.4 1.4 2.8

NS 0.02 0.008

years of age with lower extremity ischemia, and noted a rapid and aggressive course, with “frequent failure of primary arterial reconstructions, a need for repeated and additional revascularizations, and an unusually high amputation rate.” Stroke in particular is mainly a disease of the older population. Its occurrence in an unusually young patient should prompt an extensive evaluation for specific etiologies, including echocardiography and angiography.4 Several reports of stroke in young adults revealed a significant incidence of premature atherosclerosis.5-8 Carolei et al.9 noted that among young adults who had experienced a cerebrovascular event, carotid stenosis of 50-99% was an independent predictor of death and recurrent nonfatal stroke. Additionally, Kappelle et al.10 noted that the risks of recurrent vascular events in young adults who have had ischemic stroke are considerable. There are a number of series in the literature specifically regarding the results of CEA in younger

adults (Table V).11-17 Several of these have found that younger patients appear to be at significantly higher risk for recurrent carotid stenosis than older patients.11,13-15 Additionally, extensive studies of patients who develop recurrent stenosis have found that the age at initial presentation is significantly younger than for those patients who remain free of recurrent carotid disease following CEA.18 Analysis of the current large series has revealed findings similar to those of several of the studies mentioned above. We noted a significantly higher prevalence of cigarette smoking among younger patients. Younger patients were significantly more likely to be symptomatic upon presentation, in particular with a significantly higher incidence of preoperative stroke. Despite these findings, younger patients were significantly more likely to tolerate clamping of the carotid artery under regional anesthetic, suggesting increased cerebrovascular reserve. Perioperative stroke and death rates were equally low among younger and older patients. Long-term follow-up, however, revealed a significantly increased incidence of recurrent ipsilateral carotid disease, including occlusion or recurrent stenosis of the operated artery. In particular, younger patients were significantly more likely to experience severe or symptomatic recurrent stenoses requiring redo surgery. The etiologies of recurrent stenoses in younger patients appeared to be equally distributed between early neointimal hyperplasia and late recurrent atherosclerotic disease. No specific demographic factor was identified

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Table V. Series of CEA in young patients Series

Patients

Present series

94 ⱕ55 years old

Levy et al., 199711

56 ⱕ50 years old

Mingoli et al., 199712 Pedrini et al., 199113

49 ⱕ45 years old 105 ⱕ55 years old

Valentine et al., 199614

42, mean 45.5 years

Evans et al., 198715 Ballotta et al., 199917

36 ⱕ50 years old 35 ⱕ50 years old

Martin et al., 199716

26 ⱕ50 years old

Significant findings

Increased smoking, preoperative stroke, recurrent stenoses and reoperations Increased smoking, hypertension, recurrent stenoses and reoperations Poor life expectancy secondary to deaths from atherosclerosis Increased postoperative thrombosis, myocardial infarction, and recurrent stenoses Increased recurrent cerebrovascular symptoms and recurrent stenoses 6% experienced recurrent stenoses requiring reoperation Increased smoking, preoperative symptoms, preoperative stroke and contralateral occlusion; no difference in recurrent stenoses, late stroke, or survival Increased smoking and preoperative symptoms; no difference in restenosis, late stroke, or survival

among younger patients that predicted the occurrence of late occlusion or recurrent stenosis. These findings are meaningful in light of the fact that several authors have questioned the utility of surveillance duplex scans following CEA.19,20 The overall incidence of recurrent stenosis among the general population undergoing CEA is certainly low. However, our data add to the existing literature that suggests that among younger patients, the incidence of significant recurrent disease is markedly increased. Therefore, we believe that younger patients undergoing CEA need to be followed especially carefully with serial duplex scans. Although we cannot specify an exact regimen based on our data, we believe it is prudent to obtain an early scan within 3 months following surgery, and every 6 months thereafter.

CONCLUSIONS Although careful patient selection is mandatory, CEA can be performed safely in younger patients. However, during a mean of nearly 4 years of follow-up, younger patients were significantly more likely to experience a late failure of CEA, including total occlusion of the operated artery, or recurrent stenosis requiring redo surgery. Careful patient evaluation is important in choosing younger patients who require CEA. Especially in cases of asymptomatic stenosis, the risk of significant recurrent stenosis must be kept in mind. Implications of these data include mandating careful noninvasive follow-up examinations for younger patients undergoing CEA.

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