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Utility of carotid duplex in young adults with lower extremity atherosclerosis: how aggressive should we be in screening young patients?
PII: S0967-2109(97)00030-6
Cardiovascular Surgery, Vol. 5, No. 4, pp. 408–413, 1997 1997 The International Society for Cardiovascular Surgery Published by Elsevier Science Ltd. Printed in Great Britain 0967–2109/97 $17.00 + 0.00
Utility of carotid duplex in young adults with lower extremity atherosclerosis: how aggressive should we be in screening young patients? R. J. Valentine, R. T. Hagino, P. I. Boyd, H. B. Kakish and G. P. Clagett Division of Vascular Surgery, Department of Surgery, Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center, Dallas, Texas, USA The purpose of this study was to determine the prevalence and degree of carotid disease in patients with premature lower-extremity atherosclerosis. Seventy-six young men (mean age at onset of symptoms 42 ± 0.5 years with premature lower extremity atherosclerosis who underwent complete carotid duplex scans were studied. The mean lowest ankle : brachial index was 0.49 ± 0.02. Forty-seven patients (62%) required interventions to treat advanced leg symptoms, and 18 (24%) experienced disease progression during the study period. Carotid duplex scans showed internal carotid occlusions in eight (11%); advanced or critical plaque disease (60–99% diameter loss) in 14 (18%); moderate plaque disease (40–59% diameter loss) in 16 (21%); mild plaque disease (intimal thickening or 1–39% diameter loss) in 18 (24%); and normal carotid arteries in 20 (26%). Comparing the 20 subjects with normal carotid arteries to the 56 with any evidence of disease, there were no differences in age of onset, risk factors, coronary artery disease, mean ankle : brachial index, number of interventions, disease progression, amputation, or death. Fifteen (27%) of the patients with carotid atherosclerosis ultimately developed transient ischemic attack or stroke; 13 of these had advanced carotid stenoses or carotid occlusions. In conclusion, carotid plaque disease is prevalent among patients with premature atherosclerosis of the lower extremity. The presence of carotid atherosclerosis is not related to the degree of lower extremity atherosclerosis, nor to the rate of disease progression. Carotid duplex scans are indicated to screen these young patients for compelling lesions that might warrant prophylactic carotid endarterectomy. The International Society for Cardiovascular Surgery Keywords: carotid stenosis, premature atherosclerosis, young adults, risk factors
Recent epidemiologic data have proven the benefit of prophylactic carotid endarterectomy in symptomless patients with advanced internal carotid artery stenoses[1]. Carotid ultrasonography forms the basis for identification of compelling lesions in the vast majority of symptomless individuals [2]. However, use of this technique carotid ultrasonography as a screening tool in all segments of the adult population is not cost-effective. Therefore, it is appropriate to
Correspondence to: R. J. Valentine, Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas TX 75235-9157, USA
408
restrict screening to known populations of patients at high risk of carotid atherosclerosis, such as those with carotid bruits, intermittent claudication, and symptomatic coronary artery disease[2–5]. Young adults with lower-extremity atherosclerosis may represent another population at high risk for concomitant carotid atherosclerosis. The premature onset of lower-extremity atherosclerosis in young adults is associated with rapid progression of disease, high amputation rates, and poor outcome[6–10]. A high prevalence of coronary artery disease has been previously demonstrated in these patients[11]. However, the prevalence of carotid atherosclerosis, particularly advanced symptomless lesions, has not been CARDIOVASCULAR SURGERY
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Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al.
reported. The authors studied a cohort of patients with premature atherosclerosis of the lower extremity to determine the prevalence and extent of carotid atherosclerosis and hypothesized that most patients would have some degree of carotid disease and that routine screening would detect advanced symptomless stenoses. The purposes of the present study were: (i) to document the prevalence and degree of carotid disease in patients presenting with premature lower-extremity atherosclerosis; and (ii) to examine potential relationships between the degree of carotid disease relative to the degree of lower-extremity atherosclerosis and to the progression of lowerlimb disease.
Patients and methods Premature peripheral vacular disease was defined as symptomatic disease of the lower-extremity arterial circulation beginning at age 49 years or younger. This definition is based on previous data from the authors’ institution[12]. Between September 1989 and October 1996, 85 men with premature peripheral vacular disease were evaluated at the Dallas Veterans Affairs Medical Center. No women with premature peripheral vacular disease were evaluated during this time. Of the 85 men, 76 underwent complete evaluation of the extracranial carotid circulation with duplex ultrasonography. These carotid studies were performed at the time of initial evaluation as part of our institutional protocol for patients with premature peripheral vacular disease. The 76 patients with carotid studies form the basis of the present study. Some of these patients have been previously reported[8, 11]. Each patient was analyzed for symptoms of arterial disease affecting the carotid, coronary, and lowerextremity circulations. Detailed histories were obtained regarding the age at onset of lower extremity symptoms and the presence of atherosclerotic risk factors (cigarette smoking, hypertension, diabetes mellitus, and hyperlipidemia). Hyperlipidemia was defined as fasting serum total cholesterol ⱖ 240 mg/dl (6.2 mmol/l) or fasting serum triglycerides ⱖ 350 mg/dl (4 mmol/l). Medical records were scrutinized to determine documentation of carotid artery disease (head computed tomography scans, previous carotid arteriography, previous carotid endarterectomy), coronary artery disease (electrocardiograms, previous exercise or stress thallium test, coronary angiography), and leg ischemia (previous arteriography or lower-extremity revascularization procedure). The lowest recorded ankle brachial index was determined for each patient. In patients undergoing lower-extremity revascularization, the lowest preoperative ankle : brachial index was used. CARDIOVASCULAR SURGERY
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Investigations and definitions Carotid arteries were examined with color Doppler imaging and spectral analysis (Acuson 128XP Sonography System; Acuson Corp., Mountain View, CA). All studies were performed in the vascular laboratory at the Dallas Veterans Affairs Medical Center, which is accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Carotid artery stenoses were determined from measurements of peak systolic velocity, spectral broadening, and end-diastolic velocity according to suggested standards[13]. Carotid arteries were stratified into one of five categories according to the amount of plaque present in the internal carotid segment, expressed as degree of stenosis. Lack of color flow in an internal carotid artery was diagnostic of occlusion. Plaques associated with increased peak systolic flow velocities ⱖ 2.5 m/s and end-diastolic velocities ⱖ 1.1 m/s were considered to be critical (80– 99% diameter loss); those with peak systolic velocities of between 1.3–2.4 m/s were considered advanced (60–79% diameter loss). Plaques were considered to be moderate (40–59% stenosis) if there was evidence of f low disturbance without increased flow velocity. Minimal plaque disease ( ⬍ 40% stenosis) was defined as diffuse intimal thickening or as areas of discrete luminal encroachment without flow disturbance. Patients with smooth luminal surfaces and no evidence of intimal thickening were considered to have normal carotid arteries. Statistical analysis Continuous data are expressed as mean ± s.e.m. Statistical comparisons between categorical parameters were compared using the χ2 square test with Yeats correction factor. Comparisons between large groups of unpaired data were made using students t-test. Linear regression analysis was used to examine possible correlations between degree of carotid stenosis and age of symptom onset or ankle : brachial index. The Pearson correlation coefficient was used to measure the degree which two variables are linearly related. Differences were considered significant at the p ⬍ 0.05 level.
Results Mean patient age at initial evaluation was 47 ± 0.5 years, and mean age of onset of leg symptoms was 42 ± 0.5 (range, 29–49; median 43) years. There were six (8%) black patients and 70 (92%) white patients in this group, and all were men. Atherosclerotic risk factors were highly prevalent; patient demographics and risk factors are shown in Table 1. Fortynine (64%) of the patients initially presented with symptoms of intermittent claudication, 20 (26%) had rest pain, and seven (9%) had tissue loss or gan409
Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al. Table 1 Patient demographics and atherosclerotic risk factors No. of Patients Mean (s.e.m) age at onset of leg symptoms (years) Race Black White Smoking Hypertension Diabetes mellitus Dyslipidemia Initial leg symptoms Claudication Rest pain Tissue loss Cerebrovascular symptoms Transient ischemic attack Stroke Coronary artery disease
76 42 ± 0.5 6 70 69 34 11 27
(8) (92) (91) (45) (14) (36)
49 (64) 20 (26) 7 (9) 6 (8) 7 (9) 46 (61)
Values in parentheses are percentages.
grene. During a mean follow-up of 48 ± 8 months, six (8%) patients ultimately developed transient ischemic attacks, and seven (9%) ultimately had hemispheric strokes. Some 46 (60%) patients were shown to have coronary artery disease. This diagnosis was made based on prior coronary revascularization in 28 patients, on abnormal coronary angiography results in 12, and on a history of myocardial infarction in 6.
ation procedures required bypass revisions, and three others required amputation following graft occlusion. In all, nine (12%) of the 76 patients ultimately required leg amputation. Carotid duplex findings Carotid duplex results are shown graphically in Figure 1. Twenty-two patients (29%) had advanced or critical plaques, or carotid occlusions. Specifically, nine (12%) patients had stenoses associated with 60– 79% diameter loss, five (7%) had stenoses associated with 80–99% diameter loss, and eight (11%) were found to have carotid occlusions. Some 16 patients (21%) had identifiable carotid plaques associated with variable degrees of luminal encroachment and carotid flow disturbance (40– 59% diameter loss). Eighteen (24%) other patients had discrete areas of luminal thickening or minimal areas of plaque formation within the carotid bulb area. There were no identifiable areas of flow disturbance within any of these 18 carotid lesions, suggesting that the stenoses were associated with ⬍ 40% diameter loss. Twenty (26%) patients had completely normal carotid duplex scan results. There was no evidence of intimal thickening, luminal irregularity, or flow disturbance in any segment of these carotids. Subgroup analysis
Distribution of lower extremity atherosclerosis Mean ankle : brachial index among the 76 patients was 0.49 ± 0.02 (range 0.0–0.87; median 0.48). During follow-up, 47 (62%) patients required interventions for advanced symptoms of limb ischemia. Thirty-five (74%) procedures were performed to treat aortoiliac occlusive disease: 22 patients initially underwent aortofemoral bypass, ten underwent percutaneous balloon angioplasty of localized iliac artery stenoses, and three underwent femorofemoral bypasses for unilateral iliac artery occlusive disease. Twelve (26%) procedures were performed to treat femoropopliteal occlusive disease: nine patients underwent femoropopliteal bypasses, and three underwent femorotibial bypasses. Eighteen (38%) of the 47 patients who required initial interventions experienced progression of lower-extremity arterial disease. Seven patients who initially underwent aortofemoral bypass required subsequent femoropopliteal bypasses, two of which failed to result in amputation. Four other aortofemoral bypass patients required revision of aortofemoral bypass limb stenoses, three of whom required amputation after failed revascularization attempts. One of the three patients undergoing femorofemoral bypass required amputation after graft occlusion. Three of the patients undergoing infrainguinal revasculariz410
In comparing the 20 patients with normal carotid scans with the 56 with evidence of carotid plaque disease, there were no significant differences in smoking, hypertension, diabetes, dyslipidemia, or prevalence of coronary artery disease (Table 2). Similarly, there were no differences in the rates of intervention for leg ischemia, amputation, or disease progression. Fifteen (27%) of the 56 patients with carotid atherosclerosis had a history of transient ischemic attack or stroke, compared with none of the 20 with normal duplex scans (p = 0.02; Table 3). Fourteen of the 15 patients with carotid symptoms had lesions measuring 60–99% diameter loss (n = 8) or carotid occlusions (n = 6). The mean age at which leg symptoms began was 40 ± 0.9 years among patients with normal carotid duplex scans, compared with 42 ± 0.5 years among patients with evidence of carotid atherosclerosis (p = 0.01). By regression analysis, increasing age of onset correlated with degree of carotid stenosis, but differences did not reach statistical significance (r = 0.22, p = 0.05). The mean ankle : brachial index among patients with normal duplex scans was 0.55 ± 0.03, which was not significantly different compared with that of 0.48 ± 0.02 among patients with carotid atherosclerosis (p = 0.06). The degree of carotid stenosis did not correlate with ankle : brachial index by regression analysis (r = ⫺ 0.004, p = 0.97). CARDIOVASCULAR SURGERY
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Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al.
Figure 1 Distribution of carotid duplex results for the 76 study patients
Table 2 Relationship between carotid atherosclerosis and other variables
P
Duplex scan result
No. of patients Mean (s.e.m.) onset age Smoking Hypertension Diabetes Dyslipidemia Coronary artery disease Lower-extremity atherosclerosis Initial intervention Progressive disease Amputation Mean ankle : brachial index Carotid symptoms
Normal
Abnormal
20 40 16 8 5 5 10
56 42 53 26 6 22 36
± 0.9 (80) (40) (25) (25) (50)
14 (70) 5 (25) 2 (10) 0.55 ± 0.03 0
± 0.5 (95) (46) (11) (39) (64)
– 0.01 n.s. n.s. n.s. n.s. n.s.
33 (59) 13 (23) 7 (13) 0.48 ± 0.02 15 (27)
n.s. n.s. n.s. 0.06 0.02
Values in parentheses are percentages. n.s., not significant.
Table 3 Prevalence of carotid symptoms stratified by degree of carotid stenosis Symptoms
Degree of stenosis Normal
⬍ 40%
40–59%
60–79%
80–99%
Occluded
5 3
2 3
2 1
Symptomless Transient ischemic attack Stroke
20 –
18 –
15 1
–
–
–
1
1
5
Total
20
18
16
9
5
8
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Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al.
Discussion Prevention of unheralded strokes requires identification of advanced carotid stenoses in symptomless individuals. A number of subpopulations appear to have sufficiently high risk of advanced carotid disease to warrant routine screening. Previous studies have documented a 25–30% prevalence of advanced carotid disease or carotid occlusions in populations of patients with lower-extremity atherosclerosis who were unrestricted by age[3, 4]. The present data confirm that patients with premature atherosclerosis have an equally high prevalence of advanced carotid plaque disease as their older counterparts. One-half of the patients in this study with compelling lesions for carotid endarterectomy were symptomless; these lesions would not have been detected without carotid screening. Thus, carotid duplex screening appears to be justified in patients with premature lower-extremity atherosclerosis to detect symptomless, advanced plaque disease. This conclusion is in keeping with a recent publication analysing the cost-effectiveness of screening duplex scans in populations with a high prevalence of carotid lesions ⱖ 60%[14]. Should young patients with atherosclerosis of the lower extremity undergo serial duplex scans of the carotid artery? The present authors did not determine whether there was progression of carotid plaque disease in their patients. Among adults unselected by age, disease progression has been documented with serial duplex scans in symptomless patients with incidentally discovered carotid plaques[15]. The known tendency towards disease progression in patients with premature atherosclerosis of the lower extremity 6–10 is prima facie evidence that carotid plaque disease is unlikely to remain stable in the majority of young patients. The increased risk for carotid plaque recurrence following carotid endarterectomy is further indirect evidence for a tendency towards carotid disease progression in these patients[16]. Although progression of disease in the lower extremity was not associated with degree of carotid plaque disease in the present study, the authors stress that many of the carotid duplex results were based on single scans. It is possible that many patients had progression of carotid disease but remained symptomless during the study period; the authors are currently designing a prospective study to examine this issue. However, until these results are known, they recommend that young adults with lower-extremity atherosclerosis undergo screening duplex scans of the carotid artery. In patients with carotid plaque disease, duplex scans should be repeated on an annual or semi-annual basis as previously recommended[17] to detect disease progression. The authors have used previously estab412
lished criteria to determine which patients are candidates for carotid endarterectomy[1, 18]. One notable difference in the distribution of carotid disease between younger and older patients with lower-extremity atherosclerosis is the relatively higher prevalence of carotid occlusions among the young patients. Occlusions were found in 11% of the present young patients, which is higher than the 2.4% to 6% reported in older patient groups[3, 4]. The present authors submit that the higher prevalence of occluded carotid arteries in young patients may represent end-stage progression of advanced carotid stenoses that went undetected. If true, this would add further support for early carotid duplex screening in young patients with lower-extremity atherosclerosis. Despite including a large series of patients with premature atherosclerosis, there are limitations in the present study. It should be stressed that these data were collected from patients referred to a large regional Department of Veterans Affairs Medical Center. As a result, the study population may be biased towards patients with more extensive disease. In addition, the nature of the referral population resulted in an all-male study group; therefore, the findings of this study do not apply to women. In summary, carotid artery disease is prevalent in patients with premature atherosclerosis of the lower extremity. Carotid artery duplex screening is indicated to detect advanced, symptomless carotid stenoses. While the need for serial duplex scans has not been established, a program utilizing one-time duplex ultrasonography appears to be justified.
References 1. HASH(0x8a6ad4) Endarterectomy for asymptomatic carotid artery stenosis. Journal of the American Medical Association, 1995, 273, 1421–1428. 2. HASH(0x8aafa0) Carotid endarterectomy: practice guidelines. Journal of Vascular Surgery, 1992, 15, 469–479. 3. Alexandrova, N. A., Gibson, W. C., Norris, J. W. and Maggisano, R., Carotid artery stenosis in peripheral vascular disease. Journal of Vascular Surgery, 1996, 23, 645–649. 4. Marek, J., Mills, J. L., Harvich, J., Cui, H. and Fujitani, R. M., Utility of routine carotid duplex screening in patients who have claudication. Journal of Vascular Surgery, 1996, 24, 572–579. 5. Salasidis, G. C., Latter, D. A., Steinmetz, O. K., Blair, J. F. and Graham, A. M., Carotid artery duplex scanning in preoperative assessment for coronary revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke. Journal of Vascular Surgery, 1995, 21, 154–162. 6. Pairolero, P. C., Joyce, J. W., Skinner, C. R., Hollier, L. H. and Cherry, K. J., Lower limb ischemia in young adults: prognostic implications. Journal of Vascular Surgery, 1984, 1, 459–464. 7. Valentine, R. J., Premature peripheral atherosclerosis. Cardiovascular Surgery, 1993, 1, 473–480. 8. Valentine, R. J., Hansen, M. E., Myers, S. I., Chervu, A. and Clagett, G. P., The influence of sex and aortic size on late patency following aortofemoral revascularization in young patients. Journal of Vascular Surgery, 1995, 21, 296–305. 9. Valentine, R. J., Inman, M. H., Roberts, J. R., Chervu, A. and
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10.
11.
12.
13. 14.
Clagett, G. P., Late outcome of amputees with premature atherosclerosis. Surgery, 1996, 119, 487–493. Levy, P. J., Hornung, C. A., Haynes, J. L. and Rush, D. S., Lower extremity ischemia in adults younger than forty years of age: a community-wide survey of premature atherosclerotic arterial disease. Journal of Vascular Surgery, 1994, 19, 873–878. Valentine, R. J., Grayburn, P. A., Eichhorn, E. J., Myers, S. I. and Clagett, G. P., Coronary artery disease is highly prevalent among patients with premature peripheral vascular disease. Journal of Vascular Surgery, 1994, 19, 668–674. Hansen, M. E., Valentine, R. J., McIntire, D. D., Myers, S. I. and Clagett, G. P., Age-related differences in the distribution of peripheral atherosclerosis: when is atherosclerosis truly premature?. Surgery, 1995, 118, 856–863. HASH(0x9c6288) Standards in non-invasive cerebrovascular testing. Journal of Vascular Surgery, 1992, 15, 495–503. Derdeyn, C. P. and Powers, W. J., Cost-effectiveness of screening for asymptomatic carotid atherosclerotic disease. Stroke, 1996, 27, 1944–1950.
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15. Johnson, B. F., Verlato, F., Bergelin, R. O., Primozich, J. F. and Strandness, E., Clinical outcome in patients with mild and moderate carotid artery stenosis. Journal of Vascular Surgery, 1995, 21, 120–126. 16. Valentine, R. J., Myers, S. I., Hagino, R. T. and Clagett, G. P., Late outcome of patients with premature carotid atherosclerosis after carotid endarterectomy. Stroke, 1996, 27, 1502–1506. 17. Thiele, B. L., Jones, A. M., Hobson, R. W., Bandyk, D. F., Baker, W. H., Sumner, D. S. and Rutherford, R. B., Standards in noninvasive cerebrovascular testing. Journal of Vascular Surgery, 1992, 15, 495–503. 18. HASH(0x9bd580) Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. New England Journal of Medicine, 1991, 325, 445–453.
Paper accepted 24 February 1997
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Cardiovascular Surgery, Vol. 5, No. 4, pp. 408–413, 1997 1997 The International Society for Cardiovascular Surgery Published by Elsevier Science Ltd. Printed in Great Britain 0967–2109/97 $17.00 + 0.00
Utility of carotid duplex in young adults with lower extremity atherosclerosis: how aggressive should we be in screening young patients? R. J. Valentine, R. T. Hagino, P. I. Boyd, H. B. Kakish and G. P. Clagett Division of Vascular Surgery, Department of Surgery, Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center, Dallas, Texas, USA The purpose of this study was to determine the prevalence and degree of carotid disease in patients with premature lower-extremity atherosclerosis. Seventy-six young men (mean age at onset of symptoms 42 ± 0.5 years with premature lower extremity atherosclerosis who underwent complete carotid duplex scans were studied. The mean lowest ankle : brachial index was 0.49 ± 0.02. Forty-seven patients (62%) required interventions to treat advanced leg symptoms, and 18 (24%) experienced disease progression during the study period. Carotid duplex scans showed internal carotid occlusions in eight (11%); advanced or critical plaque disease (60–99% diameter loss) in 14 (18%); moderate plaque disease (40–59% diameter loss) in 16 (21%); mild plaque disease (intimal thickening or 1–39% diameter loss) in 18 (24%); and normal carotid arteries in 20 (26%). Comparing the 20 subjects with normal carotid arteries to the 56 with any evidence of disease, there were no differences in age of onset, risk factors, coronary artery disease, mean ankle : brachial index, number of interventions, disease progression, amputation, or death. Fifteen (27%) of the patients with carotid atherosclerosis ultimately developed transient ischemic attack or stroke; 13 of these had advanced carotid stenoses or carotid occlusions. In conclusion, carotid plaque disease is prevalent among patients with premature atherosclerosis of the lower extremity. The presence of carotid atherosclerosis is not related to the degree of lower extremity atherosclerosis, nor to the rate of disease progression. Carotid duplex scans are indicated to screen these young patients for compelling lesions that might warrant prophylactic carotid endarterectomy. The International Society for Cardiovascular Surgery Keywords: carotid stenosis, premature atherosclerosis, young adults, risk factors
Recent epidemiologic data have proven the benefit of prophylactic carotid endarterectomy in symptomless patients with advanced internal carotid artery stenoses[1]. Carotid ultrasonography forms the basis for identification of compelling lesions in the vast majority of symptomless individuals [2]. However, use of this technique carotid ultrasonography as a screening tool in all segments of the adult population is not cost-effective. Therefore, it is appropriate to
Correspondence to: R. J. Valentine, Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas TX 75235-9157, USA
408
restrict screening to known populations of patients at high risk of carotid atherosclerosis, such as those with carotid bruits, intermittent claudication, and symptomatic coronary artery disease[2–5]. Young adults with lower-extremity atherosclerosis may represent another population at high risk for concomitant carotid atherosclerosis. The premature onset of lower-extremity atherosclerosis in young adults is associated with rapid progression of disease, high amputation rates, and poor outcome[6–10]. A high prevalence of coronary artery disease has been previously demonstrated in these patients[11]. However, the prevalence of carotid atherosclerosis, particularly advanced symptomless lesions, has not been CARDIOVASCULAR SURGERY
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Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al.
reported. The authors studied a cohort of patients with premature atherosclerosis of the lower extremity to determine the prevalence and extent of carotid atherosclerosis and hypothesized that most patients would have some degree of carotid disease and that routine screening would detect advanced symptomless stenoses. The purposes of the present study were: (i) to document the prevalence and degree of carotid disease in patients presenting with premature lower-extremity atherosclerosis; and (ii) to examine potential relationships between the degree of carotid disease relative to the degree of lower-extremity atherosclerosis and to the progression of lowerlimb disease.
Patients and methods Premature peripheral vacular disease was defined as symptomatic disease of the lower-extremity arterial circulation beginning at age 49 years or younger. This definition is based on previous data from the authors’ institution[12]. Between September 1989 and October 1996, 85 men with premature peripheral vacular disease were evaluated at the Dallas Veterans Affairs Medical Center. No women with premature peripheral vacular disease were evaluated during this time. Of the 85 men, 76 underwent complete evaluation of the extracranial carotid circulation with duplex ultrasonography. These carotid studies were performed at the time of initial evaluation as part of our institutional protocol for patients with premature peripheral vacular disease. The 76 patients with carotid studies form the basis of the present study. Some of these patients have been previously reported[8, 11]. Each patient was analyzed for symptoms of arterial disease affecting the carotid, coronary, and lowerextremity circulations. Detailed histories were obtained regarding the age at onset of lower extremity symptoms and the presence of atherosclerotic risk factors (cigarette smoking, hypertension, diabetes mellitus, and hyperlipidemia). Hyperlipidemia was defined as fasting serum total cholesterol ⱖ 240 mg/dl (6.2 mmol/l) or fasting serum triglycerides ⱖ 350 mg/dl (4 mmol/l). Medical records were scrutinized to determine documentation of carotid artery disease (head computed tomography scans, previous carotid arteriography, previous carotid endarterectomy), coronary artery disease (electrocardiograms, previous exercise or stress thallium test, coronary angiography), and leg ischemia (previous arteriography or lower-extremity revascularization procedure). The lowest recorded ankle brachial index was determined for each patient. In patients undergoing lower-extremity revascularization, the lowest preoperative ankle : brachial index was used. CARDIOVASCULAR SURGERY
AUGUST 1997 VOL 5 NO 4
Investigations and definitions Carotid arteries were examined with color Doppler imaging and spectral analysis (Acuson 128XP Sonography System; Acuson Corp., Mountain View, CA). All studies were performed in the vascular laboratory at the Dallas Veterans Affairs Medical Center, which is accredited by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Carotid artery stenoses were determined from measurements of peak systolic velocity, spectral broadening, and end-diastolic velocity according to suggested standards[13]. Carotid arteries were stratified into one of five categories according to the amount of plaque present in the internal carotid segment, expressed as degree of stenosis. Lack of color flow in an internal carotid artery was diagnostic of occlusion. Plaques associated with increased peak systolic flow velocities ⱖ 2.5 m/s and end-diastolic velocities ⱖ 1.1 m/s were considered to be critical (80– 99% diameter loss); those with peak systolic velocities of between 1.3–2.4 m/s were considered advanced (60–79% diameter loss). Plaques were considered to be moderate (40–59% stenosis) if there was evidence of f low disturbance without increased flow velocity. Minimal plaque disease ( ⬍ 40% stenosis) was defined as diffuse intimal thickening or as areas of discrete luminal encroachment without flow disturbance. Patients with smooth luminal surfaces and no evidence of intimal thickening were considered to have normal carotid arteries. Statistical analysis Continuous data are expressed as mean ± s.e.m. Statistical comparisons between categorical parameters were compared using the χ2 square test with Yeats correction factor. Comparisons between large groups of unpaired data were made using students t-test. Linear regression analysis was used to examine possible correlations between degree of carotid stenosis and age of symptom onset or ankle : brachial index. The Pearson correlation coefficient was used to measure the degree which two variables are linearly related. Differences were considered significant at the p ⬍ 0.05 level.
Results Mean patient age at initial evaluation was 47 ± 0.5 years, and mean age of onset of leg symptoms was 42 ± 0.5 (range, 29–49; median 43) years. There were six (8%) black patients and 70 (92%) white patients in this group, and all were men. Atherosclerotic risk factors were highly prevalent; patient demographics and risk factors are shown in Table 1. Fortynine (64%) of the patients initially presented with symptoms of intermittent claudication, 20 (26%) had rest pain, and seven (9%) had tissue loss or gan409
Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al. Table 1 Patient demographics and atherosclerotic risk factors No. of Patients Mean (s.e.m) age at onset of leg symptoms (years) Race Black White Smoking Hypertension Diabetes mellitus Dyslipidemia Initial leg symptoms Claudication Rest pain Tissue loss Cerebrovascular symptoms Transient ischemic attack Stroke Coronary artery disease
76 42 ± 0.5 6 70 69 34 11 27
(8) (92) (91) (45) (14) (36)
49 (64) 20 (26) 7 (9) 6 (8) 7 (9) 46 (61)
Values in parentheses are percentages.
grene. During a mean follow-up of 48 ± 8 months, six (8%) patients ultimately developed transient ischemic attacks, and seven (9%) ultimately had hemispheric strokes. Some 46 (60%) patients were shown to have coronary artery disease. This diagnosis was made based on prior coronary revascularization in 28 patients, on abnormal coronary angiography results in 12, and on a history of myocardial infarction in 6.
ation procedures required bypass revisions, and three others required amputation following graft occlusion. In all, nine (12%) of the 76 patients ultimately required leg amputation. Carotid duplex findings Carotid duplex results are shown graphically in Figure 1. Twenty-two patients (29%) had advanced or critical plaques, or carotid occlusions. Specifically, nine (12%) patients had stenoses associated with 60– 79% diameter loss, five (7%) had stenoses associated with 80–99% diameter loss, and eight (11%) were found to have carotid occlusions. Some 16 patients (21%) had identifiable carotid plaques associated with variable degrees of luminal encroachment and carotid flow disturbance (40– 59% diameter loss). Eighteen (24%) other patients had discrete areas of luminal thickening or minimal areas of plaque formation within the carotid bulb area. There were no identifiable areas of flow disturbance within any of these 18 carotid lesions, suggesting that the stenoses were associated with ⬍ 40% diameter loss. Twenty (26%) patients had completely normal carotid duplex scan results. There was no evidence of intimal thickening, luminal irregularity, or flow disturbance in any segment of these carotids. Subgroup analysis
Distribution of lower extremity atherosclerosis Mean ankle : brachial index among the 76 patients was 0.49 ± 0.02 (range 0.0–0.87; median 0.48). During follow-up, 47 (62%) patients required interventions for advanced symptoms of limb ischemia. Thirty-five (74%) procedures were performed to treat aortoiliac occlusive disease: 22 patients initially underwent aortofemoral bypass, ten underwent percutaneous balloon angioplasty of localized iliac artery stenoses, and three underwent femorofemoral bypasses for unilateral iliac artery occlusive disease. Twelve (26%) procedures were performed to treat femoropopliteal occlusive disease: nine patients underwent femoropopliteal bypasses, and three underwent femorotibial bypasses. Eighteen (38%) of the 47 patients who required initial interventions experienced progression of lower-extremity arterial disease. Seven patients who initially underwent aortofemoral bypass required subsequent femoropopliteal bypasses, two of which failed to result in amputation. Four other aortofemoral bypass patients required revision of aortofemoral bypass limb stenoses, three of whom required amputation after failed revascularization attempts. One of the three patients undergoing femorofemoral bypass required amputation after graft occlusion. Three of the patients undergoing infrainguinal revasculariz410
In comparing the 20 patients with normal carotid scans with the 56 with evidence of carotid plaque disease, there were no significant differences in smoking, hypertension, diabetes, dyslipidemia, or prevalence of coronary artery disease (Table 2). Similarly, there were no differences in the rates of intervention for leg ischemia, amputation, or disease progression. Fifteen (27%) of the 56 patients with carotid atherosclerosis had a history of transient ischemic attack or stroke, compared with none of the 20 with normal duplex scans (p = 0.02; Table 3). Fourteen of the 15 patients with carotid symptoms had lesions measuring 60–99% diameter loss (n = 8) or carotid occlusions (n = 6). The mean age at which leg symptoms began was 40 ± 0.9 years among patients with normal carotid duplex scans, compared with 42 ± 0.5 years among patients with evidence of carotid atherosclerosis (p = 0.01). By regression analysis, increasing age of onset correlated with degree of carotid stenosis, but differences did not reach statistical significance (r = 0.22, p = 0.05). The mean ankle : brachial index among patients with normal duplex scans was 0.55 ± 0.03, which was not significantly different compared with that of 0.48 ± 0.02 among patients with carotid atherosclerosis (p = 0.06). The degree of carotid stenosis did not correlate with ankle : brachial index by regression analysis (r = ⫺ 0.004, p = 0.97). CARDIOVASCULAR SURGERY
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Figure 1 Distribution of carotid duplex results for the 76 study patients
Table 2 Relationship between carotid atherosclerosis and other variables
P
Duplex scan result
No. of patients Mean (s.e.m.) onset age Smoking Hypertension Diabetes Dyslipidemia Coronary artery disease Lower-extremity atherosclerosis Initial intervention Progressive disease Amputation Mean ankle : brachial index Carotid symptoms
Normal
Abnormal
20 40 16 8 5 5 10
56 42 53 26 6 22 36
± 0.9 (80) (40) (25) (25) (50)
14 (70) 5 (25) 2 (10) 0.55 ± 0.03 0
± 0.5 (95) (46) (11) (39) (64)
– 0.01 n.s. n.s. n.s. n.s. n.s.
33 (59) 13 (23) 7 (13) 0.48 ± 0.02 15 (27)
n.s. n.s. n.s. 0.06 0.02
Values in parentheses are percentages. n.s., not significant.
Table 3 Prevalence of carotid symptoms stratified by degree of carotid stenosis Symptoms
Degree of stenosis Normal
⬍ 40%
40–59%
60–79%
80–99%
Occluded
5 3
2 3
2 1
Symptomless Transient ischemic attack Stroke
20 –
18 –
15 1
–
–
–
1
1
5
Total
20
18
16
9
5
8
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Carotid duplex in lower extremity atherosclerosis: R. J. Valentine et al.
Discussion Prevention of unheralded strokes requires identification of advanced carotid stenoses in symptomless individuals. A number of subpopulations appear to have sufficiently high risk of advanced carotid disease to warrant routine screening. Previous studies have documented a 25–30% prevalence of advanced carotid disease or carotid occlusions in populations of patients with lower-extremity atherosclerosis who were unrestricted by age[3, 4]. The present data confirm that patients with premature atherosclerosis have an equally high prevalence of advanced carotid plaque disease as their older counterparts. One-half of the patients in this study with compelling lesions for carotid endarterectomy were symptomless; these lesions would not have been detected without carotid screening. Thus, carotid duplex screening appears to be justified in patients with premature lower-extremity atherosclerosis to detect symptomless, advanced plaque disease. This conclusion is in keeping with a recent publication analysing the cost-effectiveness of screening duplex scans in populations with a high prevalence of carotid lesions ⱖ 60%[14]. Should young patients with atherosclerosis of the lower extremity undergo serial duplex scans of the carotid artery? The present authors did not determine whether there was progression of carotid plaque disease in their patients. Among adults unselected by age, disease progression has been documented with serial duplex scans in symptomless patients with incidentally discovered carotid plaques[15]. The known tendency towards disease progression in patients with premature atherosclerosis of the lower extremity 6–10 is prima facie evidence that carotid plaque disease is unlikely to remain stable in the majority of young patients. The increased risk for carotid plaque recurrence following carotid endarterectomy is further indirect evidence for a tendency towards carotid disease progression in these patients[16]. Although progression of disease in the lower extremity was not associated with degree of carotid plaque disease in the present study, the authors stress that many of the carotid duplex results were based on single scans. It is possible that many patients had progression of carotid disease but remained symptomless during the study period; the authors are currently designing a prospective study to examine this issue. However, until these results are known, they recommend that young adults with lower-extremity atherosclerosis undergo screening duplex scans of the carotid artery. In patients with carotid plaque disease, duplex scans should be repeated on an annual or semi-annual basis as previously recommended[17] to detect disease progression. The authors have used previously estab412
lished criteria to determine which patients are candidates for carotid endarterectomy[1, 18]. One notable difference in the distribution of carotid disease between younger and older patients with lower-extremity atherosclerosis is the relatively higher prevalence of carotid occlusions among the young patients. Occlusions were found in 11% of the present young patients, which is higher than the 2.4% to 6% reported in older patient groups[3, 4]. The present authors submit that the higher prevalence of occluded carotid arteries in young patients may represent end-stage progression of advanced carotid stenoses that went undetected. If true, this would add further support for early carotid duplex screening in young patients with lower-extremity atherosclerosis. Despite including a large series of patients with premature atherosclerosis, there are limitations in the present study. It should be stressed that these data were collected from patients referred to a large regional Department of Veterans Affairs Medical Center. As a result, the study population may be biased towards patients with more extensive disease. In addition, the nature of the referral population resulted in an all-male study group; therefore, the findings of this study do not apply to women. In summary, carotid artery disease is prevalent in patients with premature atherosclerosis of the lower extremity. Carotid artery duplex screening is indicated to detect advanced, symptomless carotid stenoses. While the need for serial duplex scans has not been established, a program utilizing one-time duplex ultrasonography appears to be justified.
References 1. HASH(0x8a6ad4) Endarterectomy for asymptomatic carotid artery stenosis. Journal of the American Medical Association, 1995, 273, 1421–1428. 2. HASH(0x8aafa0) Carotid endarterectomy: practice guidelines. Journal of Vascular Surgery, 1992, 15, 469–479. 3. Alexandrova, N. A., Gibson, W. C., Norris, J. W. and Maggisano, R., Carotid artery stenosis in peripheral vascular disease. Journal of Vascular Surgery, 1996, 23, 645–649. 4. Marek, J., Mills, J. L., Harvich, J., Cui, H. and Fujitani, R. M., Utility of routine carotid duplex screening in patients who have claudication. Journal of Vascular Surgery, 1996, 24, 572–579. 5. Salasidis, G. C., Latter, D. A., Steinmetz, O. K., Blair, J. F. and Graham, A. M., Carotid artery duplex scanning in preoperative assessment for coronary revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke. Journal of Vascular Surgery, 1995, 21, 154–162. 6. Pairolero, P. C., Joyce, J. W., Skinner, C. R., Hollier, L. H. and Cherry, K. J., Lower limb ischemia in young adults: prognostic implications. Journal of Vascular Surgery, 1984, 1, 459–464. 7. Valentine, R. J., Premature peripheral atherosclerosis. Cardiovascular Surgery, 1993, 1, 473–480. 8. Valentine, R. J., Hansen, M. E., Myers, S. I., Chervu, A. and Clagett, G. P., The influence of sex and aortic size on late patency following aortofemoral revascularization in young patients. Journal of Vascular Surgery, 1995, 21, 296–305. 9. Valentine, R. J., Inman, M. H., Roberts, J. R., Chervu, A. and
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Clagett, G. P., Late outcome of amputees with premature atherosclerosis. Surgery, 1996, 119, 487–493. Levy, P. J., Hornung, C. A., Haynes, J. L. and Rush, D. S., Lower extremity ischemia in adults younger than forty years of age: a community-wide survey of premature atherosclerotic arterial disease. Journal of Vascular Surgery, 1994, 19, 873–878. Valentine, R. J., Grayburn, P. A., Eichhorn, E. J., Myers, S. I. and Clagett, G. P., Coronary artery disease is highly prevalent among patients with premature peripheral vascular disease. Journal of Vascular Surgery, 1994, 19, 668–674. Hansen, M. E., Valentine, R. J., McIntire, D. D., Myers, S. I. and Clagett, G. P., Age-related differences in the distribution of peripheral atherosclerosis: when is atherosclerosis truly premature?. Surgery, 1995, 118, 856–863. HASH(0x9c6288) Standards in non-invasive cerebrovascular testing. Journal of Vascular Surgery, 1992, 15, 495–503. Derdeyn, C. P. and Powers, W. J., Cost-effectiveness of screening for asymptomatic carotid atherosclerotic disease. Stroke, 1996, 27, 1944–1950.
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Paper accepted 24 February 1997
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