KOUJI KAJINAMI, MD,*t HIROYASU SEKI, MD,t NOBORU TAKEKOSHI, MD,t HIROSHI MABUCHI, MD* Kanazawa, Japan

Transcription

1 JACC Vol. 26, No November I, 995:209-2 Nonnvasve Predcton of Coronary Atheroscleross by Quantfcaton of Coronary Artery Calcfcaton Usng Electron Beam Computed Tomography: Comparson Wth Electrocardographc and Thallum Exercse Stress Test Results KOUJI KAJINAMI, MD,*t HIROYASU SEKI, MD,t NOBORU TAKEKOSHI, MD,t HIROSHI MABUCHI, MD* Kanazawa, Japan Objectves. Ths study was desgned to compare the usefulness of electron beam computed tomography for predcton of coronary stenoss wth that of electrocardographc (ECG) and thallum exercse tests. Background. Electron beam computed tomography can quantfy coronary calcfcatons; however, ts clncal value has yet to be establshed. Methods. Usng the volume mode of electron beam computed tomography, we studed 25 consecutve patents who underwent electve coronary angography because of suspected coronary artery dsease and compared the results wth those of ECG and thallum exercse tests. The total coronary calcfcaton score was calculated by multplyng the area (>2 pxels) of calcfcaton (peak densty > 30 Hounsfeld unts) by an arbtrarly weghted densty score (0 to ) based on ts peak densty. The mean of two scans was log transformed. Results. Calcfcaton was frst noted n women n the th decade of lfe, -0 years later than ts occurrence n men. Among patents wth advanced atheroscleross (two- and three.vessel dsease), calcfcaton scores were unformly- hgh n women but ranged wdely n men. Nne percent of patents wth sgnfcant stenoses (>75% by denstometry) had no calcfcaton. The calc- fcaton scores of patents wth sgnfcant stenoss n at least one vessel were sgnfcantly hgher than those of patents wthout sgnfcant stenoss n the study group as a whole and n most patent subgroups classfed accordng to age and gender. A cutoff calcfcaton score for predcton of sgnfcant stenoss, determned by recever operatng characterstc curve analyss, showed hgh senstvty (0.77) and specfcty (0.86) n all study patents; senstvty was smlarly hgh even n older patents (>70 years) and was enhanced n mddle-aged patents (0 to <60 years). The dfference n specfcty between calcfcaton scores and ECG exercse test results had borderlne sgnfcance (p = 0.058) and that between calcfcaton scores and thallum test results was sgnfcant (p = 0.00). The latter dfference became small but remaned sgnfcant (p = 0.0) even after the reevaluaton of thallum test results n lght of each subject's clncal data. Conclusons. Quantfcaton of coronary artery calcfcaton wth electron beam computed tomography nonnvasvely predcted angographcally confrmed coronary stenoss. Results obtaned wth ths method were at least as useful and potentally better n some patent groups than those obtaned wth thallum and ECG exercse testng. (J Am Col Cardol 995;26:209-2) Coronary artery dsease s a major cause of mortalty and morbdty n ndustralzed natons. Current methods of screenng for ths dsease, such as electrocardographc (ECG) and thallum exercse testng, can detect lesons only when they lmt coronary artery blood flow. Early pathologc studes (-5) establshed that coronary artery calcfcaton occurs n the ntma of the vessel wall and s nvarably assocated wth atherosclerotc plaque. In clncal From the *Second Department of Internal Medcne, School of Medcne, Kanazawa Unversty and tkanazawa Cardovascular Hosptal, Kanazawa, Japan. Ths work was presented n part at the 66th Annual Scentfc Sessons of the Amercan Heart Assocaton, Atlanta, Georga, November 993. Manuscrpt receved May 20, 99; revsed manuscrpt receved June, 995, accepted June 7, 995. Address for correspondence: Dr. Kouj Kajnam, Second Department of Internal Medcne, School of Medcne, Kanazawa Unversty, Takara-mach 3-, Kanazawa 920, Japan. practce, detecton of coronary artery calcfcaton by fluoroscopy (6-9) and conventonal computed tomography (0) has been both senstve and specfc for the presence of coronary artery atheroscleross. Electron beam (formerly called ultrafast) computed tomography has been found to be more senstve than fluoroscopy n detectng calcfcaton and may be useful for quantfyng coronary artery calcfcaton, thus provdng a nonnvasve method of detectng atheroscleross (-6). However, a recent comparatve study of pathologc and electron beam computed tomographc results (7) found that the degree of lumen narrowng appeared to vary wdely even when the degree of detected calcfcaton was smlar. Therefore, the value of the tomographc technque as a screenng test has yet to be establshed (8). In ths study, we assessed the relaton between the quantfcaton of coronary artery calcfcaton determned by electron 995 by lhc Amercan ('ollcgc ot ( am~l~gx ( /95/$ (95)(03-T

2 20 KAIINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS November, 995:209-2 beam computed tomography and the severty of angographcally confrmed coronary atheroscleross. We then compared the usefulness of the tomographc fndngs n the nonnvasve dagnoss of coronary atherosclerotc dsease wth that of two other screenng methods: ECG and thallum exercse testng. Methods Study patents. We prospectvely studed consecutve 25 patents (7 men and 77 women) between 6 and 86 years of age (mean [_+SD] 56 +_ ) who underwent electve coronary angography between May 99 and May 993. We excluded patents n unstable condton and those who had undergone prevous coronary nterventonal procedures (bypass surgery or angoplasty). We also excluded patents who had abnormal Q waves n two or more ECG leads because they presumably had known coronary artery dsease. In the present study, we ncluded only patents who ) presented wth chest pan (nduced by effort or occurrng at rest, or both) suggestng angna pectors, or 2) showed ECG fndngs at rest that ndcated possble myocardal schema. The youngest patent enrolled was a 6-year old male youth who had been studed because of exercse-nduced chest pan, a borderlne ECG abnormalty at rest, normal echocardographc fndngs and a strong famly hstory of coronary artery dsease. The electron beam computed tomographc study was performed wthn 2 weeks of angography n most patents; n 2 patents t was performed 2 to weeks before or after angography. Informed consent was obtaned from each patent. Ths study protocol was approved by our nsttutonal Commttee on Human Research. Segmental or dffuse coronary vasospasm (->95% by denstometry) that occurred spontaneously or was provoked by ntracoronary admnstraton of acetylcholne, reproducng chest pan and resultng n schemc ECG changes, was demonstrated on angography n 28 of 25 patents (we used acetylcholne because t could also examne endothelal dysfuncton). Although we excluded patents whose angograms showed coronary artery spasm and no atherosclerotc lesons, the ncdence of angna related to vasospasm remaned hgh n our study patents. Electron beam tomographc scannng. We obtaned 20 contguous 3-ram thck slces through the base of the heart at a 00-ms scan tme (volume mode) usng an Imatron C-00 scanner. To cover the entre coronary artery tree, addtonal slces were obtaned f necessary. The procedure was repeated wthn a few mnutes after patents were repostoned on the couch accordng to prevously establshed methods (9). Image analyss and quantfcaton. Each scan mage was evaluated by an experenced observer wthout knowledge of the clncal data. The analyss was confrmed by a cardologst and a radologst n a subsequent weekly conference, agan wthout knowledge of the clncal data. A calcfed leson was defned as havng a computed tomographc densty ->30 Hounsfeld unts (HU) wth an area ->0.5 mm 2 (2 pxels). A calcfcaton score was then determned by multplyng the area of calcfcaton by an arbtrarly weghted densty score based on the peak densty n the dentfed depost. Scorng was as follows: = 30 to 99 HU, 2 = 200 to 299 HU, 3 = 300 to 399 HU and = ->00 HU. The total coronary calcfcaton score was the sum of the scores of ndvdual lesons (,2,,5,9). As we descrbed prevously (9), the determnaton of calcfcaton score assumed a constant varance wth an ncreasng mean level, because the dfferences of the scores between repeated scans ncreased wth ther mean values. Because the radaton dose ncreases f a scan s repeated more often, we performed two scans n rapd successon n each patent. The mean of the log-transformed total coronary calcfcaton scores was subjected to subsequent analyses. The mean dfference of log-transformed calcfcaton score values between repeated scans was _ Coronary arterography. Coronary arterography was performed n multple projectons wth the use of standard technques. Each arterogram was revewed at weekly conferences by several experenced staff cardologsts who were unaware of the calcfcaton scores. The degree of coronary artery stenoss was measured by computer-asssted cnevdeodenstometry wth the use of a CCIP-30 (Cathex Inc., Tokyo, Japan). In a phantom study (20), the data obtaned from ths dgtal system were hghly correlated wth both the dameter (r = 0.9, p < 0.0) and the area (r = 0.95, p < 0.0) of actual stenoses. Sgnfcant coronary artery dsease was defned as ->75% denstometrc narrowng n any major coronary artery, ncludng dagonal and margnal vessels. Because the qualty of the angograms n 0 lesons of eght patents dd not permt denstometrc evaluaton, eght of these lesons showng ->50% dameter narrowng were consdered to have sgnfcant narrowng. Electrocardographc exercse testng. Symptom-lmted treadmll exercse testng wth the standard or modfed Bruce protocol was performed. Ischemc changes durng daly actvty had prevously been confrmed n the hosptal n 26 patents, who were classfed as havng postve exercse test results wthout a treadmll test. Exercse was contnued untl one or more of the followng end ponts were reached: ) one or more ECG leads demonstrated ->0. mv flat or downslopng ST segment depresson consstent wth schema; 2) achevement of 90% of the predcted maxmal heart rate; 3) nablty of the patent to exercse further (fatgue, dyspnea, dzzness); or ) other standard ndcatons for termnatng exercse testng (substantal blood pressure change, sgnfcant arrhythma). The followng ST segment changes were consdered to ndcate an abnormal result (postve test): ) ->0. mv depresson 0.08 s from the J pont, or 2) ->0. mv elevaton n a non Q-wave lead n a patent wthout a prevous myocardal nfarcton. The test results were revewed ndependently by two senor cardologsts who were unaware of clncal data and calcfcaton scores. Dfferences n ndvdual nterpretaton were resolved by consensus. Ischemc ST changes were observed n a sngle lead n only two patents, and both patents had sgnfcant coronary stenoses.

3 JACC Vol. 26. No. 5 KAJNAMI ET AL. 2 November. 995:209-2 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS Thallum exercse testng. All patents fasted overnght before the test. All cardoactve medcatons except sublngual ntroglycern were wthdrawn _> 6 h before the test. For each study, 3 mc ( MBq) of thallum-20 was njected ntravenously; the njecton was performed at the tme of the peak exercse acheved wth conventonal bcycle ergometry, as defned by the symptom-lmted end ponts just descrbed for treadmll exercse. The patent was then encouraged to exercse for another 60 s to ensure that the ntal myocardal uptake phase would reflect the perfuson pattern that was present at peak stress. Imagng began wthn 5 ran of njecton and was repeated 3 h later to assess the presence or absence of redstrbuton. Sngle-photon emsson computed tomographc magng was performed by usng the rotatng gamma-camera SNC-50R (Shmadzu Co., Kyoto, Japan) as follows. Images were obtaned by usng a crcular orbt over a 80 range startng at the 5 rght anteror oblque projecton and endng at the 5 left posteror oblque projecton. Each of 32 projectons was obtaned wth a 6 6 matrx for 25 s/mage. Each projecton was corrected for nonunformty wth a 00-mllon count thallum-20 flood. Projectons were obtaned by the standard fltered back-projecton technque wth the use of a Shepp-Logan flter. No scatter or attenuaton correcton was used. The long axs of the left ventrcle was dentfed from these transaxal mages, and oblque angle mages were generated n short-axs, vertcal long-axs and horzontal long-axs orentatons. Oblque angle tomograms were reconstructed on the bass of the long axs of the heart. The ntal and 3-h delayed mages were nterpreted ndependently by three experenced observers (one radologst and two cardologsts) wthout knowledge of clncal data, the results of coronary arterography or calcfcaton scores. After the short-axs, the vertcal long-axs and the horzontal longaxs vews were dsplayed, a seres of tomographc mages was analyzed to nvestgate perfuson abnormaltes. An abnormal area n the ntal mages demonstratng complete or partal redstrbuton n the delayed mages was consdered to represent myocardal schema and was classfed as a postve result. A perfuson defect that remaned unchanged n the delayed mages was consdered a myocardal scar and was also classfed as postve. Dfferences n nterpretaton among observers were resolved by consensus. These mage nterpretatons were agan performed after the clncal data of subjects were provded so that the data could be compared wth clncal results. Clncal data conssted of three groups: ) factors potentally nfluencng the procedure or mage acquston (age, gender and obesty); 2) assocated coronary rsk factors (famly hstory of coronary heart dsease, current smokng, hypertenson, dabetes melltus, low densty lpoproten cholesterol level >60 mg/d and hgh densty lpoproten cholesterol level <35 mg/dl); and 3) the reason for termnaton of exercse durng stress testng. Statstcal analyses. All statstcal analyses were performed by usng the log-transformed total coronary calcfcaton score values. The dfferences between two ndependent groups were tested by usng a nonparametrc method, the Mann-Whtney U test, because the dstrbuton of log-transformed calcfcaton score values was extremely asymmetrc n some patent groups. One-way analyss of varance was performed wth the logtransformed calcfcaton score values to analyze dfferences between subgroups wth dfferent degrees of coronary atheroscleross by usng a nonparametrc method, the Kruskal-Walls test. The ablty of the screenng method to predct angographcally confrmed coronary stenoss was evaluated by calculatng senstvty, specfcty, postve and negatve predctve values, and accuracy. Agreements between the assessments of each par from three screenng methods were nvestgated by calculaton of the kappa value. To compare ther abltes n the same sample of ndvduals, we used the McNemar test, because the proportons were pared, makng the ch-square test napproprate (2). A p value < 0.05 was accepted as statstcally sgnfcant; a p value < 0. was consdered to show borderlne sgnfcance. Results Gender dference n the relaton between coronary calcfcaton and severty of atheroscleross. Coronary artery calcfcaton was frst observed n men n the 3rd decade of lfe. Its frequency and extent gradually ncreased wth age (Fg. ). In women, coronary artery calcfcaton was frst noted n the th decade of lfe and ts ncdence ncreased markedly after the age of 50 years. Patents were classfed nto subgroups accordng to the number of vessels wth angographcally defned sgnfcant coronary stenoss. Patents wth sgnfcant stenoss n the left man trunk (n -- 2) had one or more addtonal sgnfcant coronary lesons. Thus, "vessel" refers to the rght coronary, left anteror descendng and left crcumflex coronary arteres. There were sgnfcant dfferences n log-transformed total coronary calcfcaton score levels among groups wth no, one-, two- and three-vessel dsease n the total study group, n men and n women (Fg. 2). Dstrbuton of log-transformed calcfcaton score values among four subgroups was qute smlar among all subjects and n men; these values dffered sgnfcantly between each par of subgroups, except for those wth one- and two-vessel dsease. In women, dstrbuton of logtransformed total coronary calcfcaton score values n the group wth one-vessel dsease was broad and that n the group wth two- or three-vessel dsease was narrow n comparson wth that n men. Although sgnfcant dfferences exsted among groups accordng to the number of dseased coronary arteres, values appeared to overlap (Fg. 2). Coronary artery calcfcaton was not detected n 2 (9%) of 33 patents wth sgnfcant angographcally confrmed stenoss n at least one vessel (0 of 60 patents wth one-vessel dsease and 2 of 3 wth two-vessel dsease). There was no sgnfcant dfference n gender dstrbuton of log-transformed calcfcaton scores wth regard to patent group and one-vessel dsease. In those wth two- and threevessel dsease, a hgher proporton of women than of men had

4 22 KAJINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS November, 995:209-2 TCS > > > 00 t~l a > In( +TCS) g ( 0 8 7' , 0 0 x x ee Jl x lib ~ o x = o x O O O : el( Jl ee K X X o I e ~ x oe x x x 0 K X X ~ -,., ,, :0 o x.;~ " X x O X l 2o 3o o " ;o 6o 7o " 8o 90 Age (yr)! Fgure. Age and total coronary calcfcaton score (TCS) n patents wth varous degrees of coronary atheroscleross. Correlatons between age and the logtransformed total coronary calcfcaton score [In(I+TCS)] were determned for men (closed crcles) and women (crosses) classfed by the number of vessels wth sgnfcant coronary atheroscleross (0- to 3-vessel dsease [VD]). A total of 70 men and 8 women had no sgnfcant coronary artery dsease (0 VD); 5 men and 5 women had one-vessel dsease ( VD) 35 men and 8 women had two-vessel dsease (2 VD); 2 men and 6 women had three-vessel dsease (3 VD). hgh log-transformed calcfcaton score values (Fg. ). In the group wth no-vessel dsease, ncdence and extent of coronary artery calcfcaton ncreased wth age n both men and women (Fg. ). Quantfcaton of coronary calcfcaton and nonnvasve predcton of coronary atheroscleross. Patents wth coronary atheroscleross had sgnfcantly hgher log-transformed total coronary calcfcaton score values than dd patents wthout coronary atheroscleross n the study group as a whole and among groups of patents classfed by age, except for the youngest group (Fg. 3). Ths dfference was most promnent n men aged 0 to -<60 years and n women ->60 years. A log-transformed total coronary calcfcaton score of 0 showed a senstvty and specfcty of 0.9 and 0.50, respectvely (Fg. ). A log-transformed calcfcaton score value of 3.0 was dentfed as the cutoff level wth the hghest senstvty (0.77) and the lowest false postve rate (0.)when data were analyzed wth a recever operatng characterstc curve (Fg. ). When the data for each age group were smlarly analyzed (Fg. ), the optmal cutoff level ranged from 0 to.0 (Table ), and the calcfcaton score appeared to be more predctve n mddle-aged patents (0 to -<60 years) than n the youngest (<0 years) and oldest (->70 years) groups. In addton, calcfcaton scores appeared to be more predctve n men than n women among mddle-age patents (0 to -<60 years), but more predctve n women than n men among older patents (->60 years) (Fg. ). Comparson of total coronary calcfcaton score wth exercse stress tests. The ECG and thallum exercse tests had a senstvty of 0.7 and 0.83, respectvely, and a specfcty of 0.73 and 0.60, respectvely, n the overall group of 25 patents (Tables 2 and 3). Postve test results n both stress tests and n ether test showed a senstvty of 0.65 and 0.93, respectvely, and a specfcty of 0.8 and 0.9, respectvely (Tables and 5).

5 JACC Vol. 26, No. 5 KAJINAMI ET AL. 23 November, 995:209-2l ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS +TCS W ~ ooo (D ~2 W ~ e,- C O 0C (3 E 0(] o ~ In( TCS) g'l at 7. 6 S'I 3' 2. 0 J g $ I n n t ~ I I 7O r I I ~hv N - - I 60 I 5 t r -I=# I 3 3O ## t t # I m VD VD 2 VD 3 VD Fgure 2. Total coronary calcfcaton score n patents wth varous degrees of coronary atheroscleross. The boxes ndcate the lower and upper quartles; the center lnes represent the medan. The bars below and above the boxes ndcate the 0% and 90% values, respectvely. Dfferences between pared groups were analyzed by the Mann- Whtney U test (#p < 0.05; ##p < 0.0; ###p < 0.00). Dfferences among four subgroups (0 to 3 VD) were assessed by the Kruskal-Walls test for all study subjects and for men and women. Abbrevatons as n Fgure. Mean values of log-transformed total coronary calcfcaton score n the patents wth postve results n both stress tests, those wth postve results n ether test and those wth negatve results n both stress tests were.2, 2.8, and.35, respectvely. All 26 patents who had already shown schemc ECG changes durng daly actvty n the hosptal had postve results on thallum stress testng. Accordng to the kappa values, test results among these exercse tests and electron beam computed tomographc study showed far (0.20 -< 0.0) to moderate (0.0 <- 0.60) agreement (Table 6) (2). In comparsons of senstvty and specfcty for predctng sgnfcant coronary stenoss among these three screenng methods (Table 7), sgnfcant dfferences n senttvty were observed between electron beam computed tomographc study results and postve results n both stress tests, and between electron beam computed tomographc study " results and postve results n ether stress test. Moreover, sgnfcant dfferences n specfcty were observed between results of electron beam computed tomographc study and thallum stress testng, between those of ECG and thallum stress testng, and between results of electron beam computed tomographc study and postve results n ether of these two stress tests. Dfferences n specfcty between electron beam computed tomographc study results and ECG stress testng results showed borderlne sgnfcance. Electron beam computed tomographc study appeared to be most nformatve n a mddle-age group (0 -< 60 years) (Fg. ). The valdty was compared wth that of other stress tests (Table 8). Reevaluaton of thallum mages wth clncal data decreased the number of false postve results from 8 to 33, and ncreased the number of true negatve results from 70 to 85 n the total study group; the number of true postve and false negatve results was not changed. These alteratons resulted n an ncrease n specfcty (from 0.60 to 0.72), postve predctve value (from 0.70 to 0.77) and negatve predctve value (from 0.76 to 0.8) but dd not alter the senstvty or the accuracy. In all fve subgroups classfed accordng to age, both specfcty and postve predctve value also ncreased wth the addton of clncal data, but these alteratons were statstcally nsgnfcant (data not shown). The agreement between thallum testng and electron beam computed tomographc study results ncreased from 0.3 to 0.38, whch was close to the agreement between electron beam computed tomographc study and ECG stress testng results (Table 6). Despte these alteratons, a sgnfcant dfference (p = 0.0) n specfcty between electron beam computed tomographc study and thallum results remaned. Postve predctve values for sgnfcant coronary stenoses n patents wth dscordant results on the two stress tests are shown n Table 9. Although predctve values ncreased by age (p = NS), there was no sgnfcant dfference n predctve values between these two tests showng dscordant results n the study patents as a whole, n men and women and n each age group. These data ndcated that t could not be determned whch of the dscordant tests was accurate. Dscusson The present study demonstrated several mportant new fndngs. ) Of patents wth sgnfcant coronary stenoses, -0% showed no detectable calcfcaton. 2) Gender dfferences n the amount of calcfcaton were observed. 3) Quantfcaton of coronary calcfcaton by usng recever operatng characterstc curve analyss appeared to be hghly predctve, especally n mddle-aged patents. ) Coronary calcfcaton may be at least as useful and potentally better n some patent groups than are thallum and ECG stress tests for predcton of sgnfcant coronary stenoss. Stenoses wthout calcfcaton. The prevalence and extent of coronary artery calcfcaton ncreased wth age n both men and women, even when no sgnfcant coronary stenoss was present (no vessel dsease), consstent wth fndngs of prevous

6 2 KAJINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS November, 995:209-2 I+TCS In(I+TCS) " 8. In(,TCS) ## f#~ ### ### INkY ### In(I+TCS) 9" ### " ,~ - I0 ~_~ 3",: lo " - O. n; 2 w O ~0-9" 8. ### #~ #/# # 9 ~ & ### & 00Q 7" S. *" G) 00 S". 3" O. n; " 5' - 3' " loooo ### ## 9" # 8 ### 9~ ### 8- r. loo " 6. E loo- ' " - ' n; 9 "w '", Age Group (yrs); <0 0<50 50<_60 60<70 >_70 0<_60 >_60 All Fgure 3. Total coronary calcfcaton score, accordng to age and gender, n patents wth (hatched boxes) or wthout (open bars) sgnfcant coronary atheroscleross n at least one vessel. Dfferences between the groups wth and wthout sgnfcant stenoss were assessed by the Mann-Whtney U test (#p < 0.05: ##p < 0.0; ###p < 0.00). Abbrevatons as n Fgure. Format as n Fgure 2. fluoroscopc (6-8), pathologc (2) and electron beam computed tomographc studes (,22). In the present study, two men (5 and 69 years old, respectvely) had no calcfcaton even though they were classfed as havng two-vessel dsease. One showed two stenoses wth 80% denstometrc narrowng, and the other had stenoses wth 76% and 82% narrowng. In both patents, prmary hypercholesterolema was the only rsk factor. In prevous studes usng electron beam computed tomography, the percent of patents wth clncally sgnfcant dsease who showed no detectable coronary calcfcaton vared from 0% (2) to 0.6% (23), % (), 2% (3) and 8% (6). In one of these studes (3) two of fve patents were n ther 30's. In the present study, sgnfcant stenoss wthout calcfcaton had a relatvely hgh frequency (9%) and was observed even n patents n ther 80's (Fg. ). These results suggest that clncally sgnfcant coronary atheroscleross wthout calcfcaton may be more common than prevously thought. Gender dfferences n coronary artery calcfcaton. Although the frequency of atherosclerotc coronary artery dsease dffers between men and women, only a few prevous electron beam computed tornographc studes (22,2,25) ad-

7 JACC Vol. 26, No. 5 KAJINAMI ET AL 25 November, 995:209-2 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS All subjects 0<_60 >-6O :l,r Optmal cut-off level of In(I+TCS) ;, AP eubject. I n; Men Women False-postve rate (-specfcty) False-postve rate (-specfcty) < 0 0<_50 50<_60...,... *... ~, 60<_70 > r:. []..6. o~..;./3.~ j.e.:j.8.9 " ,-.;.~ '0 ; ;..9 ;.; o. =.3..s.s.r...9 False.postve rate (-specfcty) dressed ths clncally mportant pont. In the present study, among women wth advanced coronary atheroscleross (twoand three-vessel dsease), all had elevated log-transformed total coronary calcfcaton scores (Fg. ), and the average values of log-transformed calcfcaton scores n two- and three-vessel dsease were 5.90 (n = 8) and 6.07 (n = 6), respectvely. Among men, log-transformed calcfcaton score levels were wdely dstrbuted n these groups, and the average value n patents wth two-vessel dsease was.9 (n = 35), whch was sgnfcantly lower (p < 0.05) than the value n women, and the value n patents wth three-vessel dsease was 5.5 (n = 2), whch was slghtly lower (p = NS) than that of women. Ths gender dfference has not been prevously reported, and the reasons for t are not clear. It also appeared to be the reason why n older patents (->60 years) logtransformed calcfcaton score values were more predctve n women than n men (Fg. ). In addton, coronary calcfcaton appears to develop later n women than n men, because t was frst noted n women n the th decade of lfe, -0 years later than t was noted n men. Ths observaton was consstent wth data prevously obtaned from asymptomatc subjects (22). Study patents and predcton of coronary atheroseleross. In the present study, we ncluded only patents n whom coronary artery dsease was the major problem and excluded those who had undergone emergency angography or prevous nterventonal procedures resultng n the modfcaton of atherosclerotc lesons. There were sgnfcant dfferences n Fgure. Recever operatng characterstc curves for each age subgroup Curves show data for men, women and all subjects. Optmal cutoff levels of the log-transformed calcfcaton score [In(I+TCS)] determned from these curves are nterposed. Upper panels, Results n all subjects (left), mddle-aged patents (mddle) and older patents (rght). Lower panels, Results from each age group. the prevalence of patents wth angographcally defned coronary atheroscleross between men (0 [59%] of 7) and women (29 [37%] of 77) (p < 0.00 by ch-square test) and also among groups of patents classfed by age (p < 0.00 by ch-square test) (Fg. 3). These fndngs suggested that age and gender could have affected dsease prevalence, potentally alterng the predctve values. Results of prevous studes (-6,2,25) that assessed the relaton between electron beam computed tomographc quantfcaton of coronary artery calcfcaton and clncal evdence of coronary artery dsease have vared, possbly because of dfferences n the study groups or n methods used to assess dsease. In the earlest study (3), coronary artery calcfcaton was only semquanttatvely assessed (0, + and 2+) wth 8-mm slce thckness and the number of study patents was relatvely small (n = 5). Senstvty and specfcty of postve coronary artery calcfcaton were 0.88 and.00, respectvely. The second study () had a large number of patents (n = 58) and reported hgh senstvty (0.88 to.00 among varous

8 26 KAJINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSS November, 995:209-2 Table. Valdty of Log-Transformed Total Coronary Calcfcaton Score for Predcton of Coronary Atheroscleross Postve Negatve Age Group Patents Cutoff Predctve Predctve (yr) (no.) Level Senstvty Specfcty Value Value Accuracy < (I.75 (I (0.0-(I.99) [ ) ( ( ) ( ) 0.83) 0 to <5( 7 2.) 0.86 (I ( ) ( ) (0.67-.() ( ) ( ) 50 to < ( ) ( ) ( ) ( ) ( ) 6 to -< ( ) ((t.88.2) ( ) ( ) ( ) >70 53.( (I ( ) ( ) (0.76-(I.99) ( ) ( ) All subjects 25 3.( (0.7(/-(I.82) ( ) ( ) ( ) ( ) Numbers n parentheses represent the 95% confdence nte~'al. age groups) for predctng coronary artery dsease; however. the methods used to assess the clncal evdence of coronary artery dsease were varable. Wth regard to coronary angography, only 87 patents were confrmed to have sgnfcant coronary atheroscleross, and 2 had no sgnfcant lesons. Moreover, because the majorty of the patents enrolled n that study were asymptomatc, the dsease prevalence was low (09 [9%] of 58). Therefore, hgh negatve predctve values would have been expected. The thrd study (2) usng both electron beam computed tomography and angography was performed among patents wth a hgh prevalence of dsease (7 [7%] of 00) and reported a senstvty and specfcty of 0.9 and 0.72, respectvely. That study was performed only n patents <60 years old; thus, the potental usefulness of ts fndngs for older patents could not be nvestgated. A recent study (5) focusng only on patents <50 years old reported that the detecton of coronary calcfcaton could predct sgnfcant stenoses wth a hgh senstvty (0.85) and a relatvely low specfcty (0.5). In the present study, smlar senstvty (0.83) and a sgnfcantly hgher specfcty (0.6 [p < 0.0 by ch-square analyss]) were obtaned when the results of two age subgroups (<0 years and 0 to -<50 years; Table ) were combned and a cutoff level was set at a log-transformed total coronary calcfcaton score of 0. Although there were no sgnfcant dfferences n the senstvty and postve predctve value among age subgroups, except for patents <0 years old, specfcty and negatve predctve value tended to decrease wth age (Table ). Ths trend appeared to be related to the ncrease n coronary calcfcaton assocated wth age n patents wthout sgnfcant stenoss (Fg. ). Comparson wth exercse stress tests. The number of false negatve results assocated wth ECG and thallum exercse tests usually ncreases wth patent age, because an ncreased ncdence of complcatons contrandcates a suffcent exercse challenge. In a thallum/ecg exercse test, 76%/80% and 85%/87% of patents reached a heart rate of 85% of maxmal predcted and had a rate pressure product >8,000 mm Table 2. Valdty of Electrocardographc Exercse Test for Predcton of Coronary Atheroscleross Postve Negatve Age Group Patents Predctve Predctve (yr) (no.) Senstvty Specfcty. Value Value Accuracy < ((I.33-.7) ( ) ( ) (0.76-l.07) (0.7-.0) 0 to < ( ) ( ) (0.3.:}-0.79) ( ) ( ) 50 to -< ( ) (0.5-(I.86) ( ) ( ) ( ) 60 to -< (I ((I ) ( ) ( ) ( ) ( ) ->7) ((I.57-(I.87) (0.56 (I.97) ( ) ( ) ( ) All subjects ( ) ( ) ( ) ( ) ( ) Numbers n parenthescs represent the 95% confdence nterval.

9 JACC Vol. 26, No. 5 KAJINAMI ET AL. 27 November, 995:209-2 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS Table 3. Valdty of Thallum Exercse Test for Predcton of Coronary Atheroscleross Postve Negatve Age Group Patents Predctve Predctve (yr) (no.) Senstvty Specfcty Value Value Accuracy < (l.00) ( ( ) (.00) ( ) 0 to -< (.00) ( ( ) (.0O) ( ) 50 to -< (] ( ) ( ) ( ) ( ) ( ) 60 to -<7(I ( ) ( ) ( ) ( ) ( ) -> ( ( ) ( ) ( ) ( ) All subjects 25 l ( ) ( ) ( ) ( ) ( ) Numbers n parentheses represent the 95% confdence nterval. Hg/mn, respectvely. However, these proportons decreased wth age, and n the group ->70 years old, the former proporton was 58%/62% and the latter was 75%/78%, respectvely. Accordngly, nsulfcent exercse could explan our fndng that the negatve predctve value of both stress tests decreased wth age (Tables 2 and 3). The thallum test n the present study was assocated wth a hgh false postve rate, resultng n low levels of specfcty and postve predctve value (Table 3). These factors mght be the major reason for the greater utlty of the electron beam computed tomographc study; however, t appeared that both patent background and methodologc factors were responsble for ths hgh false postve rate. In the present study, the ncdence of angna pectors related to coronary vasospasm (28 [%] of 25) was relatvely hgh. Among those patents, seven reported chest pan only at rest, and four and seven, respectvely, showed ST segment elevaton and depresson on treadmll testng. Ths fndng ndcated that patents wth vasospasm could not be dentfed from the clncal and ECG nformaton. Sgnfcant stenoses were observed n 2 of these 28 patents. Among 6 patents wth mld stenoses, 5 showed a postve thallum test (fxed defect n 2 and partal redstrbuton n 3), even though most of them ( of 6) had negatve results on treadmll testng. Although only 2 patents had a clncal epsode of chest symptoms on the day of the thallum study, 9 (68%) of 28 patents showed the perfuson abnormalty n the terrtory of the artery n whch coronary vasospasm was demonstrated. Therefore, t s possble that some thallum abnormaltes were produced not by exercse-nduced or recent spontaneous coronary vasospasm but by other undetermned factors related to vasospastc angna pectors. Interpretaton of the thallum test results mght also contrbute to the hgh false postve rate of ths test. Among men, 28 (6%) of 7 showed false postve results, and perfuson abnormaltes n anteroseptal, nferor and (postero) lateral walls were observed n 8, and 6 men, respectvely. Ther log-transformed total coronary calcfcaton score values were Among women, 20 (26%) of 77 were judged to Table. Valdty of Postve Test Results on Both Thallum and Treadmll Exercse Tests for Predcton of Coronary Atheroscleross Postve Negatve Age Group Patents Predctve Predctve (yr) (no.) Senstvty Specfcty Value Value Accuracy <0 b (} ( ) ( ) (/.33-.7) ( (0.7-l.0) 0 to < ( ) ( ) (0,3-(I.9) ( ) (0.70-0,92) 50 to -< , (0,9-0.8) (0, ( ) ( ) ( ) 60 to <7) ,82 (I ((I ) (0.68-(}.97) ( ) ( ) (0.63-0,83) -> {).58 I) (/ ( ) (0,6-.J (0,7-.0l) ( ) ( ) All subjects 25 [}.65 (I ( ) ((t (0.86-(I.97) ( ) ( ) Numbers n parentheses represent the 95q~ confdence nterval.

10 28 KAJINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS November, 995:209-2 Table 5. Valdty of Postve Test Results on Ether Thallum or Treadmll Exercse Tests for Predcton of Coronary Atheroscleross Postve Negatve Age Group Patents Predctve Predctve (yr) (no.) Senstvty Specfcty Value Value Accuracy < (.00) ( ) ( ) (.00) ( ) 0 to -< (I.00) (0.-0.7) ( ) (.00) ( ) 50 to < ((I.77-.0) ((I.2(t-0.53) ( ) ( ) ( ) 60 to -< (I.5 (I ( ) ( (I) ) ( ) ( ) > (I.59 (I ( ) ) ( ) ( ) ( ) All subjects 25 (I.93 (I ( ) ( ) ( ) ( ) ( ) Numbers n parentheses represent the 95q~- confdence nterval. have a false postve test, and the perfuson abnormaltes just descrbed were detected n 7, and 2 patents, respectvely. The log-transformed calcfcaton score values were After clncal data were gven, the number of false postve results decreased from 28 to 22 among men and from 20 to among women. Most of these alteratons were based on data relatng to gender, obesty and the reasons for exercse termnaton. After these changes, false postve perfuson abnormaltes n the anteroseptal, nferor and lateral walls, respectvely, were agan observed n 6, 0 and 6 men and n 2, 7 and 2 women. These data suggest that the attenuaton defects by the daphragma (nferor wall) n both men and women and those by the breasts (anteror wall) n women mght be overread n ntal nterpretatons. The senstvty and specfcty of clncal thallum tests for patents wth suspected coronary artery dsease n our nsttuton were and 0.75, respectvely. Thus, the hgh false postve rate resultng n the low specfcty of our thallum study could be due to both a hgh ncdence of coronary vasospasm and bas n mage nterpretatons. The thallum stress test protocol of ntal and 3-h delayed mages used n the present study mght overcall the ncdence of myocardal scar. Table 6. Agreements Between Screenng Methods 95% Kappa Confdence Methods Value lnterval EBCT vs. ECG t) EBCT vs. TI I) ECG vs. TI I) EBCT vs. (ECG and TI) EBCT vs. (ECG or TI) 0, EBCT - total coronary calcfcaton score obtaned by electron beam computed tomography; ECG = electrocardographc exercse test; TI = thallum exercse test; ECG and 33 postve results on both stress tests; ECG or TI - postve results on ether stress test. Methodologc lmtatons. The results mght have dffered had a dfferent patent group been studed. The rate of postve and negatve predctve values would have been lower and hgher, respectvely, f we had studed subjects wth a very low dsease prevalence, such as asymptomatc young healthy subjects. The effects of the study group on the results obtaned may also apply to those related to patent dstrbuton by age and probably by gender. A recever operatng characterstc curve analyss (2) s a graphc approach to determnng the best cutoff level for makng a decson based on a contnuous measurement. Although a smlar method was used n a prevous study wth electron beam computed tomography (), dsease prevalence was much lower n that study (09 [9%] of 58) than n the present study (33 [53%] of 25); therefore the data n the two studes cannot be drectly compared. Determnaton of the cutoff level requres assessment of the clncal mpact (not necessarly fnancal cost) assocated wth false postve and negatve results. In the present study, we assumed that the negatve mpact of false postve results was equal to that of false negatve results and defned the cutoff level as the pont nearest the top left corner of the curve. Determnaton of the best cutoff level for log-transformed total coronary calcfcaton score would also dffer, dependng on the background characterstcs of the patents studed. The quantfcaton system used n our study may have nfluenced the results. Vsualzaton of calcfcaton only n the dstal porton of coronary arteres appeared to be very rare n a prevous report ( of 58) () and also n the present study ( of 25). Thus, we consdered that the results would be unchanged f we studed only calcfcaton n the proxmal porton of coronary arteres. The "arbtrarly weghted densty score" s another varable n our quantfcaton system. It s not clear that the scorng system used n our study s the optmal method, and we are currently nvestgatng other quanttatve methods. For example, we have tred to calculate the sum of

11 3ACC Vol. 26, No. 5 KAJINAMI ET AL. 29 November I. 995:209-2 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS Table 7. Comparson of Senstvtes and Specfctes of Screenng Methods for Predctng Coronary, Atheroscleross Methods Age Group Patents EBCT vs. EBCT vs, EBCT vs. (yr) (no.) ECG EBCT vs. TI ECG vs. TI (ECG and Yl) (ECG or Tl) < 0 6 NS/NS NS/0.3 NS/0.02 NS/NS NS/0.3 0 to -~50 7 NS/0.076 NS/ /NS NS/NS NS/ to -<60 57 NS/NS NS/0.08 NS/0.2 NS/NS NS/ to -<70 78 NS/ /0.05 NS/NS NS/ /0.00 > NS/NS NS/NS NS/NS 0.2/NS NS/NS All subjects 25 NS/0.058 NS/ / /NS 0.00/0.000 The senstvty/specfcty values of three screenng methods (Tables I to 5) are compared by McNemar test usng ch-square dstrbuton wth degree of freedom, and ther p values are represented (NS; p -> 0.2). Abbrevatons as n Table 6. the calcfed plaque area (ram 2) n a selected age group (0 to -<60 years). Wth recever operatng characterstc curve analyss, we obtaned values for senstvty (0.82) and rate of false postve results (0.7) smlar to those of the present study. Thus, the nfluence of the arbtrarly weghted densty score on our results mght not be large. In addton, total coronary calcfcaton score was the only method used n several prevous electron beam computed tomographc studes (,2,,5,22,26; thus, the results we obtaned can be drectly compared wth prevous data. We performed two scans n the present study. There was no sgnfcant dfference n ther mean log-transformed total coronary calcfcaton score values (2.83 and 2.78); however, the greatest dfference was Thus, t s lkely that results would dffer f the logtransformed calcfcaton score values from a sngle scan were subjected to the study. The present nvestgaton focused only on quantfcaton of total coronary calcfcaton. Therefore, log-transformed calcfcaton score values dd not reflect the presence of a sgnfcant stenoss only n areas of calcfcaton. Although our study was performed prospectvely, determnaton of the ndcatons for angography mght be partly nfluenced by the stress test results. A revew of the clncal records of the enrolled patents showed that the results of ECG and thallum exercse tests appeared to nfluence the decson to perform angography for only eght and three patents, respectvely. If these patents were excluded, all values of senstvty and specfcty and predctve values changed by 0.5% to 2.%. Therefore, we consdered that a post-test referral bas had lttle effect on the obtaned results. The physologc nformaton nherent n the ECG stress test s not avalable from electron beam computed tomography or thallum stress testng. Ths fact appeared to be one of the major lmtatons of the magng rnodalty used n our study. Clncal mplcatons. In mddle-aged patents wth chest pan, the electron beam computed tomographc study predcted the exstence of coronary stenoss (Tables 7 and 8). Moreover, n patents wth prevously demonstrated myocardal schema, negatve results obtaned by computed tomography could suggest other causes of myocardal schema such as coronary vasospasm. Indeed, among 6 mddle-aged patents (from 0 to -<60 years) wth a negatve computed tomographc study, 5 showed postve results on ECG stress Table 8, Valdty of Postve Test Results Among Patents 0 to -<60 Years Old Postve Negatve Predctve Predctve Test Senstv b' Specfcty Value Value Accuracy EBCT* ( ) ( ) ( ) (0,8-0.96) ( ) TI 0, ~ ({L8-0.99) ( ) ( ) ( ) ( ) ECG :, (0.57-0,85) ( ) ( ) (0.69-0,89) ( ) ECG and T (I ( ) ( ) ((I.6(I-0.88 ( ) ( ) ECG or TI (I) ( ) (0.2-(I.65) (0,8-.0 ( ) *The optmal cutoff level of the log-transformed total coronab' calcfcaton score was determned to be 2.0 by recever operatng characterstc curve. Dfferences n senstvty and specfcty between electron beam computed tomography (EBCT) and each of the other four tests were assessed by the McNemar test usng ch-square dstrbuton wth degree of freedom, and only those wth p < 0. were ndcated (?p = 0.002, :[:p = 0.062, p = 0.00). Numbers n parentheses represent the 95% confdence nterval. Abbrevatons as n Table 6.

12 220 KAJINAMI ET AL. JACC Vol. 26, No. 5 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS November, 995:209-2 Table 9. Postve Predctve Values for Sgnfcant Coronary Stenoses n Patents Wth Dscordant Results on Electrocardographc and Thallum Stress Tests T Postve and ECG Negatve Age Group (yr) All Subjects Men Women T Negatve and ECG Postve All Subjects Men Women < ) 0. ( /6) (0/0) '0 <50 0. (3/') (/2) 0.00 (0/2) (0l) 50 <6) IL33 (3/3) (2/7) 0.20 (/) (0/3) 60 -<7/ /) (/} I).55 (5/'3) (/2) > (6/3) ((ll0j 0.83 (5/'0) (0/) All subjects 0. (20/7) (3) 0.8 (/6) (/7) Numbers n parentheses ndcate the number of patents wth sgnfcant stenoss/those free from sgnfcant stenoss. Abbrevatons as n Table 6. testng, and 0 (67%) of the 5 showed coronary vasospasm. Of the remanng fve patents, three (two men and one woman) had sgnfcant coronary stenoses wth exercsenduced chest pan, and two had no sgnfcant lesons. In older patents (>-70 years), the nonnvasve character of computed tomography appears to be especally useful. Because the valdty of electron beam computed tomographc study n ths age group was smlar to that of stress tests (Table 7), we would recommend the computed tomographc study as the frst examnaton for these patents n whom coronary artery dsease s suspected, f ts fnancal cost decreases. Among young patents, especally those <0 years old, the utlty of electron beam computed tomographc quantfcaton remaned controversal, as recently shown by others (5). In ths age group, ECG exercse stress testng may be most useful (Tables to 3). In vew of the gender dfference n the recever operatng characterstc curve analyss (Fg. ), electron beam computed tomographc study can be strongly recommended for older women (->60 years). By contrast, n mddle-aged patents (0 to -<60 years), t appears to be more useful for men than for women. Although electron beam computed tomography has the potental advantage of beng quantfed, further studes wll be requred to determne ts etfcacy and cost-effectveness. Conclusons. Nonnvasve quantfcaton of coronary artery calcfcaton usng electron beam computed tomography showed hgh senstvty and specfcty for predctng angographcally defned coronary atheroscleross. The valdty of ths method was strongest n mddle-aged patents and was not dmnshed n older patents. Electron beam computed tomographc study appeared to be at least as useful and potentally better n some patent subgroups than are thallum and ECG exercse tests for predcton of clncally sgnfcant coronary stenoss. We express specal thanks to staff cardologsts (Sensyu Hfum, MD and colleagues) and techncans n Kanazawa Cardovascular Hosptal for ther assstance n data collecton and mage analyses. References. Blankenhorn DH, Stern D. Calcfcaton of the coronary arteres. A JR (Am J Roentgenol) 959;8: Eggen DA, Strong JP, McG[l HC. 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Crculaton 985;7: Loecker TH, Schwatz S, Cotta CW, Hck.man JR Jr. Fluoroscopc coronary artery calcfcaton and assocated coronary dsease n asymptomatc young men. J Am Coll Cardol 992;9: IlL Renmuller R, Lpton MJ. Detecton of coronary artery calcfcaton by computed tomography. Dynamc Cardovasc Imagng 987;: Agatston AS, Janowtz WR, Hndner FJ, Zusmer NR, Vamonte M, Detrano R. Quantfcaton of coronary artery calcum usng ultrafast computed tomography. J Am Col Cardol 990:5: Breen JF, Sheedy PF, Schwartz RS, et al. Coronary artery calcfcaton detected wth ultrafast CT as an ndcaton of coronary artery dsease. Work n progress. Radolo~, 992;85: Tanenbaum SR. Kondos GT, Veselk KE, Prendergast MR, Brundage BH, Chomka EV. Detecton of calcfc deposts n coronary arteres by ultrafast computed tomography and correlaton wth angography. Am J Cardol 989;63: Borman JL, Stanford W, Stenberg RG, et at. Ultrafast computed tomographc detecton of coronary artery calcfcaton as an ndcator of stenoss. 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13 JACC Vol. 26, No. 5 KAJINAMI ET AL. 22 November, 995:2(9-2 ELECTRON BEAM COMPUTED TOMOGRAPHY TO PREDICT STENOSIS JA. Nonnvasve defnton of anatomc coronary artery dsease by ultrafast computed tomographc scannng: a quanttatve pathologc comparson study. J Am Col Cardol 992;20: Commttee on Advanced Cardac Imagng and Technology and Commttee on Newer Imagng Modaltes. AHA medcal/scentfc statement. Potental value of uttrafast computed tomography to screen for coronary artery dsease. Crculaton 993;87: Kajnam K, Sek H, Takekosh N, Mabuch H. Quantfcaton of coronary artery calcfcaton usng ultrafast computed tomography: reproducbl~ of measurements. Coron Artery Ds 993;: Akyama T, Dcgawa T, Kakuda T, et al. Vdeodenstometrc measurements of coronary stenoses. Comparatve study between Vanguard XR-70 and CCIP-30 [abstract]. J Jpn Col Angol 99;3:08. [n Japanese] 2. Altman DG. Practcal Statstcs for Medcal Research. London: Chapman & Hall, 99: Janowtz WR, Agatston AS, Kaplan G, Vamontc M Jr. Dffercnces n prevalence and extent of coronary artery calcum detected by ultrafast computed tomography n asymptomatc men and women. Am J Cardol 993;72: Stanford W, Breen J, Thompson B, et al. Can the absence of coronary calcfcaton on ultrafast CT be used to rule out non-sgnfcant coronary artery stenoss? [abstract]. J Am Coll Cardol 992;9 Suppl A:89A. 2. Cole TJ, McKay MG, Whte ML, Thompson B, Wnnford MD, Stanford W. Detecton of coronary artery dsease usng coronary calcfcaton by ultrafast computed tomography: results n women versus men. [abstract]. Crculaton 993;88(Pt 2):I Rumberger JA, Schwartz RS, Smons DB, Sheedy P, Edwards WD, Ftzpatrck LA. Relaton of coronary calcum determned by electron beam computed tomography and lumen narrowng determned by autopsy. Am J Cardol 99;7: Janowtz WR, Agatston AS, Vamonte M Jr. Comparson of seral quanttatve evaluaton of calcfed coronary artery plaque by ultrafast computed tomography n persons wth and wthout obstructve coronary artery dsease. Am J Cardol 99;68:-6.