Correlating carotid artery stenosis detected by panoramic radiography with clinically relevant carotid artery stenosis determined by duplex ultrasound

Correlating carotid artery stenosis detected by panoramic radiography with clinically relevant carotid artery stenosis determined by duplex ultrasound Dov M. Almog, DMD,a Tuvia Horev, DMD, MPH, PhD,b Karl A. Illig, MD,c Richard M. Green, MD,d and Laurie C. Carter, DDS, MA, PhD,e Rochester, NY, and Richmond, Va UNIVERSITY OF ROCHESTER AND VIRGINIA COMMONWEALTH UNIVERSITY

Objective. We sought to assess the utility of panoramic radiography as an adjunct screening tool for detecting significant asymptomatic carotid artery stenosis. The specific aim was to correlate calcifications seen in the region of the carotid bifurcation with clinically relevant carotid artery stenosis as determined by duplex ultrasound (DUS). Study design. Routine dental panoramic films of patients 55 and older (n ⫽ 778) at the University of Rochester Eastman Dental Center were retrospectively reviewed for calcifications around the carotid bifurcation. Patients with such calcifications were referred for DUS, and raw data were interpreted by a vascular surgeon blinded to the radiographic findings. Groups were compared by using the ␹2 test. Results. Twenty-seven patients (3.5%) had suggestive radiographic calcifications on one or both sides, 20 of whom consented to DUS. Clinically significant carotid stenoses (⬎50% lumenal narrowing) were present in 50% of the sides with calcification compared with 21% of the sides without (P ⫽ .08, ␹2). Three patients (15% of those screened with DUS) had stenoses greater than 80% and underwent 4 carotid endarterectomies as a direct result of screening. Conclusions. Data suggest that clinically significant stenosis may exist if calcifications are observed on panoramic radiographs. Incidental examination of this area carries a minimal cost and appears beneficial as a screening tool for carotid disease, although definitive testing must follow. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:768-73)

Cerebrovascular accident, or stroke, is the third leading cause of death in the United States today, exceeded only by cardiovascular disease and cancer. It is also the leading cause of severe disability and therefore represents a significant public health problem. Approximately 730,000 strokes occur per year in the United States, leading to estimated costs of $40 billion annually.1-2 Fifteen percent are hemorrhagic strokes, which we can’t influence, and 85% are ischemic strokes, the incidence of which we may be able to lower. Of the latter, more than half are believed to be the result of atherosclerotic disease at the carotid bifurcation associated with embolization of atherosclerotic debris or a a

Associate Professor, Prosthodontics, University of Rochester Eastman Dental Center, New York. b Visiting Professor, University of Rochester Eastman Dental Center, New York. c Associate Professor of Surgery, Division of Vascular Surgery, University of Rochester, New York. d Professor of Surgery, Division of Vascular Surgery, University of Rochester, New York. e Associate Professor, Oral and Maxillofacial Radiology, Virginia Commonwealth University, Richmond, Va. Received for publication Feb 25, 2002; returned for revision Jun 18, 2002; accepted for publication Jul 21, 2002. © 2002, Mosby, Inc. 1079-2104/2002/$35.00 ⫹ 0 7/16/128965 doi:10.1067/moe.2002.128965

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platelet-fibrin clot formed on the plaque surface. Carotid endarterectomy, consisting of local removal of the atherosclerotic plaque, has been conclusively shown to significantly reduce the risk of stroke in both symptomatic and symptom-free patients with significant lesions.3-5 Duplex ultrasound (DUS) is the current gold standard for the diagnosis of carotid artery stenosis (CAS). Although accurate and inexpensive, the screening of large symptom-free populations has been shown to be cost-ineffective unless the prevalence of significant disease is 4.5% or greater,6 a condition not met even when limited to the elderly. The ability to identify a group of patients in whom the prevalence of disease is greater than this would therefore be of significant benefit. The known prevalence of positive incidental carotid artery calcification(s) observed on panoramic radiographs taken for oral health reasons in the general dental outpatient population ranges from 2% to 5%, with the population age 55 and older representing the higher end of the range.7-20 Although calcifications do not imply significant stenosis and not all atherosclerotic lesions are calcified, we hypothesized that the presence of calcifications seen on dental radiographs would be associated with significant carotid disease at a high enough frequency to make this finding a cost-effective incentive for the use of DUS.

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Fig 1. The panoramic radiograph of this 66-year-old woman shows an irregular cervical soft tissue radiopacity on the right side, inferior to the angle of the mandible.

The specific objective of this study was to determine the predictive value of incidental radiographic calcifications seen in the region of the carotid artery for clinically significant carotid stenosis. MATERIAL AND METHODS From January 1, 1996, to March 31, 1999, all panoramic films used as part of routine dental care on patients 55 years of age and older at the University of Rochester Eastman Dental Center (New York) were retrospectively reviewed for the presence of incidental calcifications in the region of the carotid bifurcation. All panoramic radiographs were obtained with a Panoral model A4 (Sybron Ritter Corporation, Rochester, NY). The unit was operated at 6 to 8 mA and 75 to 90 kVp (depending on the patient’s estimated jaw size). Kodak dental film (DFG-5) with Kodak X-Omatic regular intensifying screens (Eastman Kodak Co, Rochester, NY) was used. Exposed panoramic radiographs were processed according to the manufacturer’s recommendations in an A/T 2000 automatic film processor (Air Techniques, Inc, Hicksville, NY). A total of 778 diagnostic panoramic radiographs were included in the retrospective review. A standard viewing dental box was used to examine panoramic radiographs in subdued ambient light. A hot spot illuminator (Infab Corporation, Camarillo, Calif) was used to examine the presence of carotid artery calcifications appearing as heterogeneous radiopacities in a verticolinear orientation adjacent to the hyoid bone, epiglottis, and the cervical vertebrae at or above or below intervertebral space C3-4. An oral and maxillofacial radiologist (L.C.C.) confirmed all the positive findings.

After an interexaminer variability study19 with a ␬ statistic of 0.87 (95% confidence interval, 0.81-0.92), indicating good interexaminer agreement, a final list positive for the presence of calcifications in the region of the carotid bifurcation was established (Figs 1 and 2). When such calcifications were identified, the patient and the primary care physician were contacted. A letter was sent to the primary care physician, noting that although DUS based on calcifications seen on panoramic radiographs is not the current state of practice, a number of case reports have demonstrated an association of such calcifications with significant CAS. It was then left up to the primary care physician’s discretion whether to refer the patient for DUS evaluation. DUS was performed by either radiologic or vascular surgery-based ultrasonographers. Although a variety of equipment was used, all studies were performed on modern color-flow machines. Raw data were obtained from each laboratory and coded (by using both velocity and B-mode data) according to conventional criteria21-23 by a vascular surgeon blinded to the original panoramic results (K.A.I.). Although all patients with calcifications on either or both sides were included, each side was analyzed separately. For purposes of this study, significant carotid disease was defined as a stenosis of greater than or equal to 50%, the level at which regular periodic surveillance would be instituted. Groups were compared by using the ␹2 test.24-25 Carotid DUS performed on the 66-year-old woman represented in Fig 1 revealed 60% to 74% stenosis of the right internal carotid artery with an elevated peak systolic velocity of 137 cm/s. The peak end-diastolic

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Fig 2. The panoramic radiograph of this 77-year-old woman shows a radiopacity on the left side in the area of the bifurcation, inferior to the hyoid bone, distal to the hyoid cartilage, and adjacent to the epiglottis.

velocity was 38.4 cm/s. We believe that in symptomfree patients without major medical illnesses, the risk/ benefit ratio favors operation when the peak systolic and end-diastolic velocities approach 300 cm/s and 100 cm/s, respectively. In this case, regular periodic surveillance was instituted. DUS performed on the 77-year-old woman represented in Figures 2 and 3 revealed signs of critical 60% to 80% stenosis bilaterally, although there was no calcified plaque on the right side. RESULTS Twenty-seven patients had calcifications seen in the region of one or both carotid bifurcations (prevalence, 3.5%). Of these 27, 4 were deceased at the time we attempted to contact them, 1 had moved out of state and could not be contacted, 1 refused further work-up, and 1 physician refused to send his patient for DUS evaluation. Thus, 20 patients underwent DUS, yielding a total of 40 sides (right and left) to analyze. Of the 40 sides, 26 had calcifications and 14 did not. Clinically significant carotid stenoses were present in 50% of sides with calcification versus 21% of those without (P ⫽ .08, ␹2). Three symptom-free patients with no prior transient ischemic attacks, cerebrovascular accidents, or bruits (15% of those screened with DUS) were found to have stenoses greater than 80% and underwent 4 carotid endarterectomies; all 3 had calcifications seen on panoramic radiographs, and none were previously thought to have had carotid disease. The DUS results of both the right and the left sides are displayed in Tables I, II, and III. DISCUSSION Atherosclerosis tends to accumulate within the bifurcation of the common, external, and internal carotid

Fig 3. Anteroposterior cervical spine projection taken on the individual represented in Fig 2. Note the absence of calcified plaque on the right side.

arteries and produces symptoms as plaque forms on the irregular surface and embolizes to the brain. This plaque can be removed surgically— but at the cost of possibly creating a stroke during the surgery itself. To determine appropriate treatment for varying degrees of carotid stenosis, a number of randomized, controlled clinical trials took place between 1991 and 1995, in-

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Table I. DUS results, panoramic positive sides (n ⫽ 26/40) Results

No. of sides

Percent stenosis 1-15 16-49 50-79 80-99 Occluded Total positive sides

9 4 9 3 1 26

DUS, Duplex ultrasound.

Table II. DUS results, panoramic negative sides (n ⫽ 14/40) Results

No. of sides

Percent stenosis 1-15 16-49 50-79 80-99 Total negative sides

8 3 3 0 14

Table III. Percent stenosis (⬍50% vs 50% or more)

Panoramic positive results Panoramic negative results Total sides

⬎50%

⬍50%

No. of sides

13 (50%) 3 (21%) 16

13 11 24

26 14 40

P ⫽ .08, ␹2 test; P ⫽ .10, Fisher exact test.

cluding the North American Symptomatic Carotid Endarterectomy Trial,3,4 the Asymptomatic Carotid Atherosclerosis Study,5 the European Carotid Surgery Trial,26 and the Efficacy of carotid endarterectomy for asymptomatic carotid stenosis study.27 In general, net benefit occurs with operation in symptomatic patients with ⬎50% stenosis and in symptom-free patients with ⬎60% stenosis (although in practice, a cutoff of ⬎80% for symptom-free patients is more common). Unfortunately, the first clinical manifestation of CAS is often a completed stroke that occurs when treatment is too late. The issue of screening has therefore been examined extensively, with disappointing results to date. Angiography carries sufficient morbidity to eliminate it as a practical screening tool.5 Although DUS is noninvasive and relatively inexpensive, screening all patients is impractical and cost-ineffective. In a recent mathematical analysis exploring this issue, Yin and Carpenter6 found that ultrasonic carotid screening was

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cost-effective only if the prevalence of significant disease in the screened population was at least 4.5%. The prevalence of severe disease, even in those over the age of 65 years, has been estimated to be less than 1%6; therefore, screening all patients, even just the elderly, is not a reasonable strategy. Obviously, identifying a subgroup of patients in whom the prevalence of disease is high (more than 4.5%) would allow more cost-effective ultrasonic screening. Suggestions for high-risk groups in whom DUS screening might be cost-effective include those with bruits or atherosclerosis in other parts of the body. Audible cervical bruits are caused by turbulent blood flow and can be caused by tortuosity, high flow rates through otherwise normal vessels, or a cardiac problem, in addition to CAS. Although the presence of a bruit does not necessarily indicate CAS, most physicians believe that its presence increases the odds of CAS being present— enough so that ultrasonic evaluation is indicated.28-30 In addition, because the incidence of significant CAS in patients with lower extremity atherosclerosis or coronary atherosclerosis is as high as 10% to 12%,31-33 occlusive disease in either location has become a de facto indication for carotid DUS. To date, however, there are no universally accepted screening criteria, and referral for ultrasonic evaluation remains at the discretion of the individual physician. In recent years, a number of publications have described the detection of calcifications in the region of the carotid bulb on panoramic radiographs.7-20 These studies suggested an overall prevalence rate of carotid artery calcifications on panoramic radiographs of approximately 2% to 5% in the general dental outpatient population and approximately 5% in patients 55 years of age and older. No data yet exist on the relationship among these calcifications, significant CAS, and actual stroke risk. Our data suggest that if calcifications are present, the prevalence of significant CAS is 50% (defined as that requiring future surveillance or operation, or both), well over the point at which subsequent ultrasonic testing is cost-effective. Calcifications exhibited a strong trend (P ⫽ .08) toward a higher predictive value for significant CAS than did their absence (50% vs 21%), but it should be noted that even in sides where calcifications were not seen, the predictive value for significant CAS in patients with any calcification at all was still well over the point of cost-effectiveness. In other words, a patient with any calcification on either side has a high (at least 21%) likelihood of having significant CAS on one side or the other. It should be noted that as a direct consequence of this study, operable lesions were found and corrected in 3 patients who had no other indication of CAS and were not otherwise being screened.

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Not all atherosclerotic lesions are calcified; furthermore, the presence of calcification in this location is not a definitive indicator of vascular disease. However, because calcification is such a common component of atherosclerotic plaques, the presence of calcification lying over the course of a blood vessel commonly affected by this disease would suggest some degree of atherosclerosis. In fact, calcification-lined arteries are commonly seen on plain radiographs of both the lower extremities and abdomen and commonly trigger further evaluation.31 The utility of the algorithm proposed here obviously will depend on the prevalence and amount of calcification within these lesions, which is as yet unknown. Finally, it should be emphasized that the finding of calcification near the carotid bifurcations on dental panoramic radiographs is not proposed as a screening tool for CAS per se, but rather as a trigger for subsequent cost-effective ultrasonography. We also do not advocate obtaining panoramic radiographs solely to screen for carotid bifurcation disease; although the rate of calcification may be significant, all noncalcified lesions will be missed and the false-negative rate will thus be unacceptably high. We do believe, however, that these data convincingly show that the presence of calcifications near the carotid bifurcation on radiographs obtained for another reason should not be ignored. CONCLUSION Many patients undergoing dental examination and treatment undergo panoramic radiography as part of their routine care.34-37 These radiographs include, in most cases, the region of the carotid bifurcation bilaterally. Our data suggest that patients with visible calcification on either side during routine dental panoramic radiography have rates of significant CAS high enough to make subsequent DUS a cost-effective procedure. In other words, useful data are provided at no additional cost or morbidity, and if this finding is ignored, the opportunity to prevent potential stroke may be missed.

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4.

5. 6. 7. 8.

9. 10. 11. 12.

13. 14. 15. 16.

17. 18.

19.

20.

We would like to thank the University of Rochester Craniofacial Diagnostic Imaging Lab (New York) for their administrative and technical support.

21.

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33. Erdoes LS, Marek JM, Mills JL, Berman SS, Whitehil T, Hunter GC, et al. The relative contributions of carotid duplex scanning, magnetic resonance angiography, and cerebral arteriography to clinical decision making: a prospective study in patients with carotid occlusive disease. J Vasc Surg 1996;23:950-6. 34. Joseph LP. The selection of patients for x-ray examinations: dental radiographic examinations. United States Department of Health and Human Services Public Health Service, Food and Drug Administration. HHS Publication no. (FDA) 88-8273; 1987. 35. Anonymous. Recommendations in radiographic practices: an update. Council on dental materials, instruments, and equipment. J Am Dent Assoc 1989;118:115-7. 36. Kogon S, Bohay R, Stephens R. A survey of the radiographic practices of general dentists for edentulous patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:365-8. 37. Scandrett FR, Tebo HG, Quigley MB, Miller JT. Radiographic examination of edentulous patient. Part I: review of literature and preliminary report comparing three methods. Oral Surg Oral Med Oral Pathol 1973;35:266-74. Reprint requests: Dov M. Almog, DMD University of Rochester Eastman Dental Center 625 Elmwood Ave Rochester, NY 14620 [email protected]