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The Relevance of Detecting Carotid ArteryCalcification on Plain Radiograph

Ian Doris, MD; Julian Dobranowski, MD; Arlene A. Franchetto, MD; Roman Jaeschke, MD

Background and Purpose: The aim of this study was to determine the potential value of carotid arterycalcification observed on plain radiographs in patients referred for carotid angiogram in the diagnosis ofcarotid artery stenosis.Methods: One hundred sixty consecutive patients with suspected carotid artery stenosis underwent both

plain radiographs of the carotid arteries and digital subtraction angiography of the same vessels. Inaddition, 108 of these patients also had duplex ultrasound of the same vascular area. The clinicalusefulness of the carotid artery calcification was assessed by calculating the likelihood ratios for differenttest results against results of angiography and duplex ultrasound.

Results: There is a statistically significant association between the degrees of calcification and carotiddisease as demonstrated by angiography (P=.0001), although positive correlation of the degrees ofstenosis and calcification was only fair (Spearman correlation coefficient r=.4). The sensitivity of carotidcalcification in detecting clinically significant stenosis assuming any calcification is abnormal was 89%with a specificity of 46%. The likelihood ratios for 50o stenosis by angiography varied from 0.24 (nocalcification) to 3.41 (level III) and for 50% stenosis by duplex ultrasound varied from 0.21 (nocalcification) to more than 5.87 (level III). Assessments of the degree of calcification based on plainradiographs had excellent reproducibility (all intraclass correlation coefficients were greater than .9).

Conclusions: In this population with a high prevalence of carotid artery disease, there is an associationbetween the presence of carotid calcification and atheromatous disease. If subsequent studies were to showthis to apply in the general population, this could be of value in identifying asymptomatic patients atincreased risk. (Stroke. 1993;24:1330-1334.)KEY WoRDs * angiography, digital subtraction * carotid artery diseases * ultrasonics

C erebral vascular disease is frequently associatedwith atherosclerotic changes involving the ca-rotid arteries. Atherosclerosis is a gradual pro-

gressive disease process in which atheroma may ulceratethrough the endothelium, exposing underlying collagenand thereby initiating the process leading to thrombusformation. This thrombus may then act as a source ofcerebral emboli. Cerebral ischemia may also occur inthe absence of ulceration if the atheroma enlarges andcauses stenosis of the carotid artery severe enough toreduce pressure and flow distally in the artery. Theyearly risk of cerebral infarction is estimated to be from1% to 3% in patients with asymptomatic carotid arterialdisease and from 5% to 7% in patients with stenotic orulcerative atherosclerotic lesions of the carotid arteries,with the majority of strokes occurring without precedingtransient ischemic attacks.1-3 Secondary prevention inthe form of reduction of risk factors, pharmacotherapy,or surgical intervention has been shown to reduce theincidence of cerebrovascular accidents in symptomatic

Received April 27, 1993; accepted April 29, 1993.From the Department of Radiology, Hamilton General Hospi-

tal (I.D., A.A.F.); the Departments of Radiology (J.D.) andMedicine (R.J.), St. Joseph's Hospital; and the Departments ofDiagnostic Imaging (I.D., J.D., A.A.F.) and Medicine (R.J.),McMaster University Centre, Hamilton, Ontario, Canada.

Reprint requests to Ian Doris, MD, Department of Radiology,Hamilton General Hospital, 237 Barton St E, Hamilton, Ontario,Canada L8L 2X2.

patients.4 One could therefore postulate that the iden-tification of carotid atherosclerosis and/or stenosis, bothsymptomatic and asymptomatic, may be important inreduction of morbidity and mortality. Such identifica-tion may be accomplished (or at least suspected) on thebasis of history of symptoms and signs suggestive of aneurological disease, the finding of carotid artery bruiton clinical examination, or imaging studies includingangiography and ultrasound.We have evaluated the potential role of carotid artery

calcification observed on the plain radiograph in thediagnosis of patients with suspected carotid artery ste-nosis. The starting point is an observation that calcifi-cation of the coronary arteries has been found in certainpopulations to be a useful marker of significant coro-nary artery disease89 and to have prognostic signifi-cance.10-13 Although carotid artery calcification hasbeen described previously,14"5 the clinical significanceof this finding has not been established. Carotid arterycalcification can be identified on radiographs of thecervical spine, skull, facial bones, and chest. In anautopsy study of 25 patients, Bostrom and Hassler15found a correlation between the degree of calcificationand the occurrence of fibrous plaque at the carotidbifurcation. Imataka et al16 found that carotid calcifica-tion correlated with severe generalized atherosclerosisand found a higher incidence of hypertension, glucoseintolerance, and stroke in their study group. Culebras etal17 studied carotid calcification by computed tomogra-

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Doris et al Carotid Calcification of Arterial Stenosis 1331

phy and discovered an association between the degreeof calcification and luminal stenosis. Calcification wasmore commonly associated with severe stenosis thanany other morphological feature of atheroma.The purpose of our study was to establish the possible

relation between carotid artery calcification found onthe plain radiographs of the region of carotid arteriesand the severity of arterial stenosis. By using intrave-nous digital subtraction angiography (IVDSA) and du-plex ultrasound (DUS) as criterion measures ("goldstandards"), the following questions were addressed:(1) What is the association between the degree ofcarotid artery calcification and the degree of angio-graphically and ultrasonographically established steno-sis? (2) What is the intraobserver and interobservervariability in detecting and classifying the degree ofcarotid artery calcification? (3) What are the odds thata significant carotid stenosis would be present in apatient with a given level of carotid calcification; inother words, what are the likelihood ratios of carotidartery stenosis associated with different levels of carotidartery calcification?

Subjects and MethodsPopulationWe studied 160 consecutive patients referred for

IVDSA because of clinically suspected extracranial ca-rotid disease. These patients included 111 men with amean age of 62 years and 49 women with a mean age of65 years. Patient clinical histories included transientischemic attack, reversible ischemic neurological deficit,progressive stroke, and completed stroke. Patientsyounger than age 40 and female patients considered atrisk for pregnancy were excluded from the study. Thestudy was approved by the hospital ethics committee,and informed consent was obtained from all patients.

Imaging MethodsThe IVDSA studies were all performed using the

DVI2 system (Philips Medical Systems, Toronto, On-tario, Canada) using an image intensifier of 6 inches andan imaging matrix of 502 pixels. The carotid arterialcirculation was imaged from the level of the aortic arch toits intracranial portion. Each angiographic examinationwas performed by injection of 25 mL of Omnipaque 350into a peripheral vein.18 Views were obtained in both theanteroposterior and 300 to 40° oblique projections.At the time of the angiographic study, a short run

(approximately three to five frames) of 105-mm cinefilm was obtained (without intravenous contrast) at thelevel of the carotid bifurcation to document the pres-ence and the extent of carotid artery calcification. Thepositioning of the patient was determined fluoroscopi-cally. The degree of stenosis as assessed by visualinterpretation by the radiologist performing the exami-nation was subsequently correlated with the presenceand extent of calcification obtained on the 105-mm film.Although angiography is considered to be the optimal

method of estimation of the degree of arterial stenosis,many patients have DUS examination before referralfor angiography. We decided to correlate the results ofthe DUS carotid studies if performed within 3 monthsof the angiograms. We believed that this would be ofvalue because DUS studies are more likely to be the first

line of assessment of symptomatic patients and as a safenoninvasive procedure are more likely to be used inpopulation screening and epidemiological studies. Itshould be noted, however, that only patients having astenosis of greater than 50% would be referred for angi-ography, thereby introducing a bias toward a more severestenosis in this group of patients. The criterion for stenosisof 50% or greater was an average velocity ratio of 1.5between the internal and common carotid arteries withspectral broadening in the internal carotid artery systolicwave. The DUS studies were performed using a DiasonicsWIDE VUE (St Hiliaire, Quebec, Canada) mechanicalsector scanner with a frequency of 7.5 to 10 mHz, using astandoff pad. One hundred eight patients who were re-ferred for angiography had had DUS studies performedwithin 3 months of angiography.

Classification of CalcificationThe classification of calcification was based on the

morphological appearance on the 105-mm films. Thecalcifications were either punctate or linear. (Linear wasdefined as calcified plaque continuous for at least 5 mmas measured directly from the 105-mm film or a series ofcalcified plaque separated by no more than 1 mm.Estimated minification factor for this equipment was0.78.) No attempt was made to classify the calcificationbased on the location of the calcification within thearterial wall.

Grading was based on a system of 0 through 10, with0 being no calcification, with progression from singleand multiple punctate calcification to linear plaque onone side of the artery, on two opposite sides, andcontinuous across both sides of the artery. In grade 10the calcification was completely circumferential (Fig-ure). For further statistical analysis we combined calci-fication grades 1 and 2, 3 through 6, and 7 through 10into level I, level II, and level III calcification, respec-tively. Each patient was assigned a single grade ofcalcification, which was the highest grade of calcificationirrespective of the side of calcification. Similarly, thegrade of stenosis assigned to the patient was the mostsevere stenosis, irrespective of side. We have postulatedthat carotid artery stenosis of 50% or more is clinicallysignificant. The radiologists examining the plain radio-graphs of the carotid arteries were blinded to the resultsof the IVDSA or DUS and to patient identification.

Statistical MethodsTo test the reproducibility of carotid artery calcifica-

tion classification, two of the authors (I.D. and A.A.F.)conducted an interobserver and intraobserver study toassess the agreement as to the grade of calcification.The radiologists were blinded to patient identification.The chance-corrected agreement was calculated usingan intraclass correlation coefficient (ICC, equivalent toweighted K). This analysis was performed both for 10grades and for three levels of calcification.The association between the degree of carotid artery

calcification (three levels) and the degree of angio-graphically established stenosis (no stenosis vs less than50% stenosis vs 50% to 99% stenosis vs completeocclusion) was measured by X 2 and the Spearmancorrelation coefficient.To assess the value of carotid artery calcification

observed on plain radiograph in the diagnosis of carotid

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1332 Stroke Vol 24, No 9 September 1993

3 4 5 6

Schematic representation illustrating grading of calcification.Top panel, Level I classification (grades 1 and 2). Grade 1,Single punctate (<5 mm) area of calcification. Grade 2,Multiple punctate areas ofcalcification. Middlepanel, Level IIclassification (grades 3 through 6). Grade 3, Single linear (>5mm) area of calcification. Grade 4, Single linear calcificationand single punctate calcification. Grade 5, Single linearcalcification and multiple punctate calcifications. Grade 6,Two linear areas of calcification. Bottom panel, Level IIIclassification (grades 7 through 10). Grade 7, Two linearareas of calcification and one punctate area of calcification.Grade 8, Two linear areas of calcification and multiple areasof calcification. Grade 9, Three linear areas of calcification.Grade 10, Continuous calcification with no visible breaks.

artery stenosis, we calculated the likelihood ratio for50% stenosis associated with different levels of carotidartery calcification (using IVDSA and DUS as goldstandards).19 Using likelihood ratios, we then estab-lished the posttest probability of significant carotidartery stenosis in patients with given pretest probabilityand given findings of carotid artery calcification on plainradiograph.

ResultsCarotid arterial calcification was identified in 118

(73.8%) of the 160 patients studied. The prevalence ofcalcification increased with age from 43.7% in the groupaged 40 to 49 years to 81.5% in patients aged older than65 years. None of the patients aged younger than 50years had a calcification grade of greater than 6; grade9 and 10 calcifications were found exclusively in patientsaged older than 65 years.The ICC quantifying chance-corrected agreement for

the 121 radiographs that were interpreted by two radi-ologists was .92 for 10 grades and .91 for three levels.The chance-corrected agreement for repeated assess-ment done by the same radiologist was .92 (10 grades)and .91 (three levels) for one radiologist (59 studies)(I.D.) and .94 (10 grades) and .97 (three levels) for the

TABLE 1. Relation Between Degree of Carotid Artery Stenosisby Intravenous Digital Subtraction Angiography and Level ofCarotid Artery Calcification by Plain Radiograph

Stenosis of carotid artery (%)Level of Nocalcification 100 50-99 <50 stenosis Total

III 4 14 4 0 22II 7 27 12 4 50I 11 18 10 7 46No calcification 0 10 14 18 42Total 22 69 40 29 160

P=.0001, X2=39.86, Spearman correlation coefficient r=.4.

second radiologist (58 studies) (A.A.F.). In each case,ICC was statistically significant (P<.01).Twenty-nine (18%) of the patients did not have any

stenosis detected on IVDSA; 91 (57%) of 160 patientshad 50% or more carotid artery stenosis. Table 1displays the maximum level of calcification comparedwith the maximum degree of stenosis present onIVDSA. The statistical association between calcificationand carotid stenosis was highly significant (x2=39.865df=9, P=.0001). However, although correlation be-tween the relative disease and calcification was positive,the association was only fair (Spearman correlationcoefficient r=.4).Data showing discrimination between clinically signif-

icant carotid artery stenosis (50% or more) and lack ofor nonsignificant carotid artery stenosis (less than 50%)are presented in Table 2, which also displays thelikelihood ratios associated with different levels of cal-cification. Likelihood ratios ranged from 0.24 for nocalcification to 3.41 for level III.The corresponding data for 108 patients who under-

went DUS evaluation of the carotids are presented inTables 3 and 4. There was significant correlation be-tween the presence of carotid stenosis established byDUS (X2=36.55 df=9, P=.0001) and only fair correla-tion between the relative degrees of calcification andstenosis (Spearman correlation coefficient r=.38,P=.0001). The likelihood ratios ranged from 0.21 for nocalcification to more than 5.87 for level III calcification.

Analysis of the degree of stenosis on the same side asthe calcification showed no statistically validassociation.

DiscussionThe purpose of this study was to establish whether a

reproducible system of grading of calcification could be

TABLE 2. Relation Between Presence of Significant CarotidArtery Stenosis by Intravenous Digital Subtraction Angiographyand Level of Carotid Artery Calcification by Plain Radiograph

Stenosis of carotidLevel of artery (%) Likelihoodcalcification 250 <50 ratioIII 18 4 3.41II 34 16 1.61I 29 17 1.29No calcification 10 32 0.24Total 91 69

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Doris et al Carotid Calcification of Arterial Stenosis 1333

TABLE 3. Relation Between Degree of Carotid Artery Stenosisby Digital Ultrasound and Level of Carotid Artery Calcificationby Plain Radiograph

Stenosis of carotid artery (%)

Level of Nocalcification 100 50-99 <50 stenosis Total

III 3 13 0 0 16II 2 26 5 0 33I 7 20 9 1 37No calcification 1 7 9 5 22Total 13 66 23 6 108

P=.0001, X2=36.55, Spearman correlation coefficient r=.38.

designed and if a relation exists between the presenceand extent of carotid arterial calcification and thedegree of stenosis.The findings in this study allow several conclusions.

First, we have established that the assessment of thedegree of carotid artery calcification is a highly repro-ducible procedure, with the degree of reproducibilitysimilar to other diagnostic tests.20We have found that the degree of association be-

tween the degrees of calcification in carotid disease asassessed by IVDSA and DUS was significant (P=.0001),but correlation between the grade of calcification andthe degree of stenosis was at best fair (Spearmancorrelation coefficient r=.40 for IVDSA and .38 forDUS). Thus, our findings identify carotid artery calci-fication on plain radiograph as a marker for significantextracranial carotid disease. The importance of thisobservation is similar to previously reported significantcorrelation between coronary artery calcification onplain radiograph (or on autopsy) and presence of coro-nary artery disease.'1

Third, by using IVDSA (and, separately, DUS) as agold standard we calculated the likelihood ratios char-acterizing carotid artery calcification observed on plainradiograph as a test and established test properties thatdo not depend on the prevalence of disease. The clinicalusefulness of the likelihood ratios associated with dif-ferent results of carotid artery calcification on plainradiograph is illustrated in Table 5. This table examinesfour different scenarios: patients with low (5%), inter-mediate (25%), and high (75%) pretest probability (orprevalence) of significant carotid artery stenosis, as wellas the population of our study (in whom the prevalenceof significant stenosis was 57%). Using likelihood ratiosestablished for carotid artery calcification observed onplain radiograph against stenosis demonstrated by

TABLE 4. Relation Between Presence of Significant CarotidArtery Stenosis by Digital Ultrasound and Level of CarotidArtery Calcification by Plain Radiograph

Stenosis of carotid

Level of artery (%) Likelihoodcalcification >50 <50 ratio

III 16 0 >5.87II 28 5 2.06I 27 10 0.99No calcification 8 14 0.21Total 79 29

TABLE 5. Posttest Probability of Significant Carotid ArteryStenosis Given Varying Pretest Probabilities and Different Resultsof Carotid Artery Calcification on Plain Radiograph (IntravenousDigital Subtraction Angiography as Gold Standard)

Level of Pretest probability (%)calcification 5 25 57 75

III 15 53 82 91II 8 35 68 83I 6 30 63 79No calcification 1 7 24 42

Values are percentages.

IVDSA, data from this table show that in patients withlow probability of significant stenosis (5%) the lack ofany visible calcification brings the risk of significantstenosis down to 1%. At the same time, a high grade ofcalcification detected in such patients increases the riskof having significant disease to 15%.Of note is that calculations presented in Table 5

require the assumption that the properties of the test(likelihood ratios) do not change with different preva-lence of the disease in the examined population. Al-though somewhat controversial, such an assumption iscertainly safer for likelihood ratios than for other com-mon descriptors of the usefulness of diagnostic tests, ie,sensitivity and specificity.21Although the specificity is poor, this may be a reflec-

tion of the high prevalence of disease in this patientpopulation. However, in Table 1 several patients withcarotid occlusion had low grades of calcification. Thismay reflect the complex mechanism of production ofsymptoms in these patients, and this study did not takeinto account phenomena such as embolism or acutethrombosis in association with minor degrees of steno-sis. However, we feel that the results of this study justifya larger prospective study in a group that more accu-rately reflects the prevalence of disease in the generalpopulation. In this respect the study of Loecker et a122 isworthy of comparison. In this study, a significantlyincreased risk of coronary artery disease in asymptom-atic young men was demonstrated in the presence offluoroscopically visible coronary artery calcification; anegative result for coronary calcification indicated a lowrisk of coronary disease.

If the relation demonstrated in this study were shownby a prospective study to apply in the asymptomaticpopulation, then it would appear to have potential inidentifying individual at-risk patients before the onsetof symptoms. Plain radiography of the neck for detec-tion of calcification is inexpensive, quick and easy toperform and interpret, and requires no specializedequipment or training, all of which would be advantagesin any potential screening tool. The presence or absenceof a significant stenosis could easily and safely beestablished thereafter by DUS.

Clearly, with readily available and safe methods ofassessing carotid stenosis such as DUS and IVDSA, wedo not consider detection of carotid artery calcificationas being of any relevance or value in symptomaticpatients. However, our findings suggest that carotidartery calcification may be useful in identifying asymp-tomatic at-risk individuals with significant carotid arterystenosis and may be an early marker of evolution of the

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1334 Stroke Vol 24, No 9 September 1993

disease. We believe that this relation merits a prospec-tive study in an asymptomatic at-risk population.

Finally, how may the risk of stroke be reduced? Therole of active medical intervention has not yet beendetermined. The recent Veterans Affairs CooperativeStudy indicates that carotid endarterectomy in asymp-tomatic patients reduced the incidence of ipsilateraltransient ischemic attacks but did not reduce the risk ofstroke or death.23 However, epidemiological studieshave identified the major risk factors as hypertension,elevated cholesterol, and smoking. All of these may bereduced either by therapeutic intervention in the high-er-risk group or by life-style modification in the generalpopulation.24 Identification of patients in the earlystages of carotid atheromatous disease may aid ineffective implementation of such life-style modificationand could ultimately assist in reduction of the occur-rence of stroke.

AcknowledgmentThis study was supported in part by the Hamilton (Ontario)

Civic Hospitals.

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I Doris, J Dobranowski, A A Franchetto and R JaeschkeThe relevance of detecting carotid artery calcification on plain radiograph.

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 1993 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Stroke doi: 10.1161/01.STR.24.9.1330

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