Reproducibility of Noninvasive Ultrasonic Measurement of Carotid Atherosclerosis. The Asymptomatic Carotid Artery Plaque Study

Transcription

1 1062 Reproducibility of Noivasive Ultrasoic Measuremet of Carotid Atherosclerosis The Asymptomatic Carotid Artery Plaque Study Ward A. Riley, PhD; Ralph W. Bares, PhD; William B. Applegate, MD; Robert Dempsey, MD; Tyler Hartwell, PhD; Vicki G. Davis, DrPH; M. Gee Bod, PhD; ad Curt D. Furberg, MD, PhD Backgroud ad Purpose: To determie the effect of a lipid-lowerig aget ad/or a low-dose atithrombotic aget o the progressio of early-stage carotid atherosclerosis, oivasive B-mode ultrasoud was used to measure itimal-medial thickess i asymptomatic idividuals with moderately elevated lipids as part of the ogoig multiceter Asymptomatic Carotid Artery Plaque Study. Methods: Uiform ultrasoic scaig ad readig protocols were implemeted to obtai maximum itimal-medial thickess measuremets i 12 stadard segmets i patiets havig a small to moderate wall thickess ( mm) i at least oe of the carotid arteries. Paired B-mode image recordigs o 858 patiets, performed 1 moth apart ad read at a core laboratory (each pair by the same reader), determied both withi-soographer (W, =405) ad betwee-soographer (B, =453) reproducibility. Results: The primary ed poit (mea±sd), deed i each idividual as the mea value of the 12 maximum itimal-medial thickess measuremets, was 1.31 ±0.21 mm (W) ad ±0.22 (B) at the time of the secod examiatio. The mea differece i the primary ed poit (exam 2-exam 1) was ±0.13 mm (W) ad 0.00± mm (B). The Pearso correlatio coefficiets were 0.79 (W) ad 0.75 (B). I 90% of the patiets, the absolute differece i the primary ed poit was <0.22 mm (W) ad <0.24 mm (B). Variability of the secodary ed poit, deed as the sigle largest itimal-medial thickess measuremet i a patiet, was betwee three ad four times larger tha the variability for the primary ed poit. Differeces i soographer performace betwee cliical ceters were very small. Coclusios: The results demostrate that stadardized oivasive ultrasoic techiques yield highly reproducible measures of carotid itimal-medial thickess, which ca serve as a measure of carotid atherosclerosis i cliical trials that moitor small rates of lesio progressio. (Stroke 1992;23: ) KEY WORDS carotid artery diseases cliical trials ultrasoics Soographer performace represets a critical compoet of measuremet reproducibility i populatio-based ultrasoud studies of atherosclerosis 1-4 ad i cliical research studies 5 " 7 that use as their ed poit a ultrasoicalry determied measure of atherosclerosis derived from measuremets of itimalmedial thickess (IMT). 89 Multiceter studies i particular require cosistetly high-quality stadardized B-mode images of arterial walls, give the potetial for variatio from cliic to cliic. Furthermore, stadard cliical protocols that assess arterial disease (usig agiography ad Doppler ultrasoud) focus o measuremets of arterial From the Departmets of Neurology (W.A.R., R.W.B.), Neurobiology ad Aatomy (M.G.B.), ad Public Health Scieces (W.A.R., C.D.F.), Bowma Gray School of Medicie, Wisto- Salem, N.C.; the Departmet of Prevetive Medicie (W.B.A.), Uiversity of Teessee, Memphis; the Divisio of Neurosurgery (R.D.), Uiversity of Ketucky, Lexigto; ad Research Triagle Istitute (T.H., V.G.D.), Research Triagle Park, N.C. Supported by Natioal Istitutes of Health grat R01-HL , Merck Sharp & Dohme Research Laboratories, ad E.I. DuPot De Nemours & Compay, Ic. Address for reprits: Ward A. Riley, PhD, Departmet of Neurology, Bowma Gray School of Medicie, Medical Ceter Boulevard, Wisto-Salem, NC Received March 4, 1992; accepted May 5, lume ad blood flow abormalities i cotrast to those of the artery wall. Although a umber of factors other tha soographer performace cotribute to measuremet reliability, icludig ultrasoud istrumetatio ad reader performace, the critical depedece of B-mode image quality o iterrogatio agle ad fie adjustmet of istrumet cotrols makes the role of the soographer cetral to the measuremet process. To determie the effect of soographer performace o the ed poit measuremet of atherosclerosis i the ogoig Asymptomatic Carotid Artery Plaque Study (ACAPS), we assessed both withi-soographer (W) ad betwee-soographer (B) reproducibility by comparig pairs of exams performed at 1-moth itervals. This article summarizes these results ad discusses their implicatios for moitorig small rates of chage i carotid IMT (which very likely reflect progressio/ regressio of carotid artery atherosclerosis) i multiceter cliical trials. Reproducibility results associated with the B-mode image readig process are also preseted. Subjects ad Methods The Asymptomatic Carotid Artery Plaque Study The Asymptomatic Carotid Artery Plaque Study is a double-blid, placebo-cotrolled, multiceter cliical

2 Riley et al Carotid Atherosclerosis Reproducibility: ACAPS 1063 trial of high-risk idividuals with asymptomatic carotid steosis. 10 (Participatig istitutios ad pricipal staff are listed i the Appedix.) The primary objective of ACAPS is to determie, usig a factorial desig, whether lovastati (20-40 mg/day) ad/or warfari (1 mg/day), take with aspiri (81 mg/day) over a average treatmet period of moths, retards the progressio of early atherosclerotic lesios i the carotid arteries, as measured by semiaual B-mode ultrasoud. Those eligible for participatio iclude me ad wome years of age (iclusive) who have serum low desity lipoprotei cholesterol levels of mg/dl (iclusive) but o history of myocardial ifarctio, severe agia, stroke, or trasiet ischemic attack. Subjects also must show evidece of early atherosclerotic developmet i the carotid arteries, as defied by at least oe measuremet of IMT >1.5 mm i the commo or iteral carotid artery or >1.6 mm i the bifurcatio but <3.5 mm at ay carotid site. The 0.1-mm differece betwee the lower cutoff poits for the bifurcatio (1.6 mm) ad the commo/iteral carotid arteries (1.5 mm) takes ito accout the 0.1-mm greater wall thickess i the bifurcatio compared with the other two segmets i ormal, youg adults. The qualifyig lesio must also demostrate irregular, ouiform wall thickeig, a typical characteristic of focal atherosclerotic lesios. Ultrasoic Ed Poit Measuremets ad Scaig Protocol The primary outcome measure of extet ad severity of atherosclerosis i the carotid arteries is the mea of 12 measuremets of the maximum IMT obtaied idepedetly from the ear ad far walls of three arterial segmets o each side: the ear wall ad far wall of the proximal 8 mm of the iteral carotid artery, the ear wall ad far wall of the carotid bifurcatio, begiig at the tip of the flow divider ad extedig 8 mm proximal, ad the ear wall ad far wall of the arterial segmet extedig 8-16 mm proximal to the tip of the flow divider ito the commo carotid artery. The 8-mm legth of each segmet is defied relative to the tip of the flow divider, which is ormally the most clearly defied aatomic referece i the carotid system. Figure 1 is a simplified diagram that defies the locatio of these segmets. Maximum IMT measuremets are made o these images to determie the primary ed poit. The secodary ed poit is the sigle maximum IMT of the 12 measuremets obtaied. Subjects eligible for ACAPS must have a miimum of four high-quality IMT measuremets from each carotid system. The high-resolutio B-mode ultrasoud system selected for use was the Biosoud Phase 2. Additioal istrumetatio ad equipmet required to obtai the ultrasoic B-mode image data iclude a high-resolutio S-VHS videocassette recorder, a study flow pael ad electrocardiogram marker, ad a persoal computer. I preparatio for the scaig protocol, soographers moitor istrumet performace by obtaiig stadardized images of a tissue-equivalet phatom ad storig this iformatio to provide a database that documets stability of the measuremet process over time. For the scaig protocol, soographers use a careful logitudial iterrogatio of the complete cir- Exteral Carotid Level of ^ \^1 Flow Divider """" ^t Near Wall 1 jrj / / */ 1 " Iteral Carotid 8 mm 8 mm 8 mm II Commo Carotid 1 Far Wall FIGURE 1. Simplified diagram of carotid artery, defiig segmets of arterial walls examied with B-mode ultrasoud. cumferetial extet of each arterial segmet. Image sequeces of the maximum IMT are recorded ad coded o the video image. Soographer ad Reader Certificatio The required use of two ACAPS soographers at each cliical ceter permits measuremet of both withi-soographer ad betwee-soographer measuremet reproducibility. All soographers completed a uiform 3-moth traiig program coducted by the ultrasoud ceter ad subsequetly eared certificatio o completio of the program. 10 To maitai the high quality of the ultrasoud compoet of ACAPS, ultrasoud ceter persoel perform quarterly site visits to moitor performace. I additio, ACAPS soographers must obtai aual recertificatio. Withi- ad betwee-soographer reproducibility data ad the frequecy of segmet visualizatio from baselie ad 6-moth follow-up visits serve as primary criteria i the recertificatio process. The ultrasoud readers also received certificatio o satisfactory completio of a stadard 3-moth traiig program. Like the soographers, readers must obtai aual recertificatio. Iitial ad ogoig comparisos of withi- ad betwee-reader variability data permitted cotiual assessmet of group performace. Additioal traiig ad practice were provided whe warrated based o evaluatio of idividual readig performace data. Reproducibility Measuremets The data were obtaied durig a 12-moth period from B-mode image recordigs o 858 subjects who uderwet paired ultrasoud examiatios 1 moth apart usig the uiform scaig protocols. Of the 858 patiets, 405 were examied by the same soographer ad 453 by differet soographers. I either case did soographers have access to the IMT data from the previous examiatio. This process permitted both withi-soographer ad betwee-soographer measuremet reproducibility to be idividually assessed. The cliical ceters set all ultrasoud recordigs to the ultrasoud ceter where the same reader read each pair of scas. The ACAPS readers reviewed ad read videotape sequeces for each selected arterial segmet

3 1064 Stroke Vol 23, No 8 August 1992 usig a stadardized readig protocol. The B-mode image readig statio cosisted of the followig istrumetatio: high-resolutio S-VHS videocassette recorder ad 19-ich moitor, persoal computer, ad hardware ad software for decodig arterial segmet iformatio (right/left side, ear/far wall, arterial segmet) that is placed o the audio chaels of the videocassette by the study flow pael at the cliical ceter. Durig the readig protocol, the ACAPS reader carefully reviewed the image sequeces obtaied o each segmet at slow speed or frame by frame to search for those images 1) that most clearly outlied the importat ear wall ad far wall boudaries ad 2) that demostrated the maximum IMT of the segmet. Usig the computer, the reader the captured ad stored i digital format up to three frames per segmet upo which measuremets were performed. The visualized blooditima ad media-advetitia boudaries were marked with a computer-cotrolled cross hair at 0.5-mm itervals alog the defied segmet. Three examples of these measuremets o B-mode images are show i Figure 2. From these boudary coordiates, the maximum IMT of each segmet was determied by the computer ad the atherosclerosis ed poits were calculated. The precisio with which a idividual cross hair ca be placed o a boudary, 0.05 mm, is deed by the pixel dimesio of the digitized image. The axial resolutio of the ultrasoud system is approximately mm as measured usig images from a stadard tissue-equivalet ultrasoud phatom. After trasmissio of data o all participats to the data coordiatig ceter, statistical aalyses were performed o the eligible populatio. Usig the atherosclerosis ed poits computed from each of the two exams (exam 1 ad exam 2) for each subject, we used stadard aalysis methods to determie the mea, media, stadard deviatio, ad rage for the distributio of the followig quatities withi a specific populatio subset: the ed poit at exam 2; the arithmetic differece i the ed poit (exam 2 exam 1); ad the absolute differece i the ed poit (exam 2-exam 1). Whe a exam yielded data o <12 segmets, ed poit calculatio was based o oly those segmets adequately visualized. I some idividuals, ed poits from paired exams were obtaied from the maximum IMT of differet segmets ad/or differet umbers of segmets. Stadard Pearso correlatio coefficiets were also computed for the ed poits obtaied from the two exams. Results Table 1 summarizes withi-soographer ad betwee-soographer reproducibility data o the primary atherosclerosis ed poit obtaied from pairs of exams performed 1 moth apart ad read by the same reader. Pairs of studies performed by 10 differet soographers are icluded i the data set, with each cliical ceter employig at least two soographers. The mea value of the primary ed poit at exam 2 is 1.31 mm (W) ad mm (B), with the stadard deviatio of the arithmetic differece betwee exams equal to 0.13 mm (W) ad mm (B) ad the mea absolute differece betwee exams equal to mm (W) ad mm (B). I 90% of the exam pairs, the absolute differece is <0.22 mm (W) ad 0.24 mm (B). The Pearso correlatio coefficiets (exam 1 versus exam 2) are 0.79 (W) ad 0.75 (B). Table 2 summarizes withi-soographer ad betweesoographer reproducibility data o the secodary atherosclerosis ed poit obtaied from the same pairs of exams performed 1 moth apart ad read by the same reader. The mea value of the secodary ed poit at exam 2 is 2.29 mm (W) ad 2.28 mm (B), with the exams equal to 0.45 mm (W) ad 0.50 mm (B) ad the mea absolute differece betwee exams equal to 0.31 mm (W) ad 0.36 mm (B). The Pearso correlatio coefficiets (exam 1 versus exam 2) are 0.65 (W) ad 0.58 (B). Table 3 summarizes combied withi-soographer ad betwee-soographer reproducibility data by cliical ceter. The mea primary ed poit at exam 2, the exams, the mea absolute differece betwee exams, ad the Pearso correlatio coefficiet are compared. The stadard deviatio of the differece rages from 0.12 mm to mm. The mea absolute differece rages from mm to mm, ad the Pearso correlatio coefficiet rages from 0.72 to I some idividuals, the reader could ot obtai maximum thickess data from all 12 stadard arterial segmets because the recorded sequece did ot adequately demostrate the wall boudaries ecessary for measuremet. Of the maximum attaiable six maximum thickess measuremets per side, the umber (mea±sd) for the 858 patiets durig exam 2 was 5.5±0.7 (left) ad (right). The differece betwee exams was -0.1±0.8 (left) ad -0.1±0.7 (right), showig a slight tred for fewer segmets to be visualized o the secod exam. Overall, we obtaied high-quality maximum thickess data o 92% of the arterial segmets examied. By aatomic site, the commo carotid provided the most cosistet data (99%), followed by the bifurcatio (96%) ad the iteral carotid (81%). By ear or far wall, the far wall provided the higher yield (97%) compared with the ear wall (87%). The site-specific Pearso correlatio coefficiets betwee the maximum thickess measures from repeat exams varied moderately amog the 12 sites, ragig from 0.50 to No specific patters related to aatomic locatio or ear/far wall thickess measuremets emerged i the results except for a slightly higher correlatio i the bifurcatio ragig from 0.63 to Table 4 summarizes withi-reader ad betweereader reproducibility data o the primary atherosclerosis ed poit obtaied from a radomly selected subset (10%) of exam 2 patiets. These were reread by either the same or a differet reader. Pairs of studies performed by five differet readers are icluded i the data set. The mea value of the primary ed poit at readig 2 is mm (W) ad mm (B), with the readigs (readig 2-readig 1) equal to 0.07 mm (W) ad mm (B) ad the mea absolute differece betwee readigs equal to 0.06 mm (W) ad 0.12 mm (B). The Pearso correlatio coefficiets (readig 2 versus readig 1) are 0.95 (W) ad 0.73 (B). Table 5 summarizes withi-reader ad betweereader reproducibility data o the secodary athero-

4 Riley et al Carotid Atherosclerosis Reproducibility: ACAPS 1065 FIGURE 2. Ultrasoic B-mode images of carotid artery. Ski surface is at left of image; distace scale at bottom gives tissue depth i cetimeters. Left (shallower) lie of small cross hairs, separated vertically by 0.5-mm itervals, defies blood-itima boudary. Deeper lie of cross hairs defies media-advetitia boudary. Maximum itimal-medial thickess for defied segmet is determied from relative positios of these pairs of cross hairs. Upper pael: Commo carotid. Measured segmet is located 8-16 mm proximal to tip of flow divider, which has bee marked by soographer with large cross hair positioed at top of image. Middle pael: Carotid bifurcatio. Measured segmet is located 0-8 mm proximal to tip of flow divider, which has bee marked by soographer with large cross hairpositioed approximately 8 mm dow from top of image. Lower pael: Iteral carotid. Measured segmet is located 0-8 mm distal to tip of flow divider, which has bee marked by soographer with large cross hair positioed approximately 8 mm up from bottom of image. sclerosis ed poit obtaied from the same pair of exams. The mea value of the secodary ed poit at readig 2 is 2.27 mm (W) ad 2.34 mm (B), with the readigs equal to 0.32 mm (W) ad 0.45 mm (B) ad the mea absolute differece betwee readigs equal to 0.24 mm (W) ad 0.32 mm (B). The Pearso correlatio coefficiets (readig 2 versus readig 1) are 0.76 (W) ad 0.72 (B). Discussio The results summarized i Tables 1-5 idicate that uiform traiig of persoel ivolved i a multiceter cliical trial usig stadardized scaig ad readig protocols achieves highly reliable ed poit measures of carotid atherosclerosis. Te soographers at four cliical ceters ad five readers at the ultrasoud ceter provided the results for this data set. The same reader, without prior kowledge of the maximum IMT measuremets obtaied i either examiatio, read each exam 1/exam 2 pair. The atherosclerosis ed poits are ot highly depedet o the soographer performig the sca, as evideced by the similar withi-soographer ad betwee-soographer measures of reproducibility. For example, for the primary ed poit, the stadard deviatio of the arithmetic

5 1066 Stroke Vol 23, No 8 August 1992 TABLE 1. Withi- ad Betwee-Soographer Baselie Quality Cotrol: Primary Atherosclerosis Ed Poit Primary atherosclerosis ed poit ( maximum IMT [mm]) Exam 2 measuremet Differece: exam 2-exam Absolute differece: exam Correlatio betwee exam Pearso r IMT, itimal-medial thickess to exam ad exam to differece betwee exams, 0.13 mm (W) ad mm (B), the mea absolute differece betwee exams, mm (W) ad mm (B), ad the Pearso correlatio coefficiets, 0.79 (W) ad 0.75 (B), are very similar. The correspodig stadard deviatios ad mea absolute differeces for the secodary ed poit are betwee TABLE 2. Withi- ad Betwee-Soographer Baselie Quality Cotrol: Secodary Atherosclerosis Ed Poit Secodary atherosclerosis ed poit (Sigle maximum IMT [mm]) Exam 2 measuremet Differece: exam 2-exam Absolute differece: exam Correlatio betwee exam Pearso r IMT, itimal-medial thickess to exam ad exam Withisoographer Betweesoographer Withisoographer Betweesoographer to three ad four times larger tha those for the primary ed poit. This icreased variability primarily results from the fact that the primary ed poit is the mea of 12 separate measuremets compared with oly a sigle measuremet for the secodary ed poit. For both ed poits, the withi-reader reproducibility is somewhat better tha the betwee-reader results, i most cases beig better tha withi- ad betwee-soographer reproducibility. The reproducibility data are highly cosistet betwee differet cliical ceters. Withi-soographer performace appears to be slightly better tha betwee-soographer performace whe cosiderig the 90th ad 95th percetiles for the mea absolute differece betwee exams. For the 90% level, the results are 0.22 (W) ad 0.24 (B) ad for the 95% level, the results are 0.27 (W) ad 0.31 (B). These largest differeces are due to the icomplete circumferetial scaig of oe or more of the ear or far wall segmets i a subject. This precludes visualizatio ad recordig of the true maximum thickess withi a segmet. I this situatio, the maximum thickess visualized o the tapes was measured ad was used to compute the ed poits. Over time, remedial traiig of soographers has reduced the umber of differeces >0.30 mm. I previous work, Crouse et al 5 have reported the repeatability of a scorig system for measurig the extet of carotid atherosclerosis. They obtaied the scores retrospectively from a chart review of routie cliical scas by addig the maximal lesio (wall) thickess (i millimeters) observed i 16 sites located withi the extracraial carotid system. I pairs of exams performed withi a period of 6 moths, the Pearso correlatio coefficiet was 0.86, with a summary score of Because withi-soographer reproducibility data as reported i Table 1 were ot available i the study of Crouse et al, a more detailed compariso of the two methods is difficult. Additioally, sigificat systematic differeces exist betwee the scaig/readig protocols used to obtai the summary score i the study of Crouse et al ad the methods used to acquire the atherosclerosis ed poits i ACAPS. These iclude the defiitio of boudaries defiig the arterial wall ad lesio. The multiceter B-sca Assessmet Study used sigificatly differet ed poits (IMT was ot specifically measured), traiig methods, ad scaig/readig protocols for measurig carotid atherosclerosis to obtai withi-reader ad betwee-reader repeatability data. 6 Withi- ad betwee-soographer repeatability data were ot obtaied. The Pearso correlatio coefficiets for paired repeat readigs of lesio width (thickess of lume ecroachig lesio) were 0.81 (W) ad 0.56 (B). I a sigle-ceter, populatio-based study of carotid atherosclerosis that used IMT measuremets obtaied oly from the commo carotid artery, Saloe ad Saloe 4 reported a correlatio of 0.91 betwee repeat scas performed 1 week apart by the same soographer ad read by differet readers. The stadard deviatio of the differece betwee the two results, which were themselves the mea of three idividual thickess measuremets, was 0.09 mm. The ogoig Atherosclerosis Risk i Commuities (ARIC) study provided withi-soographer reproduc-

6 Riley et al Carotid Atherosclerosis Reproducibility: ACAPS 1067 TABLE 3. Betwee-Ceter Compariso of Withi- ad Betwee-Soographer Reproducibility: Primary Atherosclerosis Ed Poit Ceter A B C D Pairs () , exam of arithmetic differece (exam 2-exam 1) absolute differece (exam 2-exam 1) Data are i terms of the mea maximum itimal-medial thickess (i millimeters). Pearso r ibility data acquired o repeat scas of oly oe arterial segmet, performed durig a sigle examiatio by the same soographer after a iterval of several miutes Correlatio coefficiets betwee far wall IMT raged from 0.67 to 0.92, depedig o the specific segmet beig scaed. The stadard deviatio of the differece of sigle site maximum IMT measuremets raged from 0.13 mm i the commo carotid to 0.39 mm i the bifurcatio. Cohort data from ARIC o withi- ad betweereader reproducibility for readigs of complete examiatios have also bee reported. 13 For maximum far wall IMT, the correlatio coefficiets raged from 0.78 to 0.92 ad the stadard deviatio of the differece was early the same for all arterial segmets, beig equal to approximately mm. Other studies curretly usig IMT measuremets to study carotid artery atherosclerosis progressio ad regressio iclude Pravastati Lipids ad Atherosclerosis i the Carotids (PLAC-2), the Multiceter Isradipie/Diuretic Atherosclerosis Study (MIDAS), ad the Carotid Artery Italia Ultrasoud Study (CAIUS) The ACAPS results reported i this TABLE 4. Withi- ad Betwee-Reader Baselie Quality Cotrol: Primary Atherosclerosis Ed Poit Primary atherosclerosis ed poit ( maximum IMT [mm]) to article, i combiatio with data from ogoig populatio-based studies, strogly suggest that B-mode image measuremets of carotid wall thickess yield reliable measures of early atherosclerosis. The adaptive respose of the arterial wall to elarge as atherosclerosis develops, ad thus to maitai a costat lume size, does ot limit the method i studyig early atherosclerosis, as is the case with other techiques that are based o the measuremet of arterial lume dimesios. With group sample sizes approachig 200 patiets, small primary ed poit differeces betwee treatmet groups (o the order of 0.03 mm or 2% of the iitial primary ed poit) are detectable with a high degree of cofidece. This should permit cliical trials focusig o primary prevetio of atherosclerosis progressio to be of relatively shorter duratio ad to have cosiderably smaller sample sizes, i cotrast to secodary prevetio cliical trials that utilize stadard morbidity ad mortality ed poits. I priciple, other arterial beds accessible to ultrasoic examiatio could be studied i a similar maer with this highly reliable, oivasive methodology. TABLE 5. Withi- ad Betwee-Reader Baselie Quality Cotrol: Secodary Atherosclerosis Ed Poit Secodary atherosclerosis ed poit (Sigle maximum IMT [mm]) Withireader Readig 2 reasuremet Differece: readig 2 readig to Absolute Differece: readig 2-readig Correlatio betwee readig 2 ad readig 1 Pearso r 0.95 IMT, itimal-medial thickess. Betweereader Withireader Readig 2 measuremet Differece: readig 2-readig to 0.54 Absolute differece: readig 2 readig Correlatio betwee readig 2 ad readig 1 Pearso r 0.76 IMT, itimal-medial thickess. Betweereader to

7 1068 Stroke Vol 23, No 8 August 1992 Appedix Participatig Istitutios The Asymptomatic Carotid Artery Plaque Study ivolves four cliical ceters, a data coordiatig ceter, a ultrasoud ceter, a lipid laboratory for serum lipid profiles, ad a admiistrative ceter. The admiistrative ceter, lipid laboratory, ad oe cliical ceter are located at the Bowma Gray School of Medicie i Wisto-Salem, N.C. The data coordiatig ceter is at the Research Triagle Istitute i Research Triagle Park, N.C. The ultrasoud ceter is at AUTREC, Ic. i Wisto-Salem, N.C. The remaiig cliical ceters are at the Uiversity of Iowa College of Medicie, Iowa City; the Uiversity of Ketucky, Lexigto; ad the Uiversity of Teessee, Memphis. Pricipal Staff Admiistrative Ceter Bowma Gray School of Medicie of Wake Forest Uiversity: Drs. Curt D. Furberg (Pricipal Ivestigator), James F. Toole, M. Gee Bod, Mark Espelad, Robert Byigto, Therese A. Dolecek, ad Susa E. Margitic; Lipid Laboratory Bowma Gray School of Medicie of Wake Forest Uiversity: Dr. Richard St. Clair (Pricipal Ivestigator) ad Nia A Stokes, Marcie Burris, Pat Shaw, Tricia Seitz, Catherie Butler, Debbie DeVaey; Data Coordiatig Ceter Research Triagle Istitute: Drs. Tyler Hartwell (Pricipal Ivestigator), Vicki Davis, David Myers ad Steve Game, Supatra Campbell, Betty Hastigs, Reee Karlse; Ultrasoud Ceter-AUTREC, Ic.: Drs. Ward A. Riley (Pricipal Ivestigator), Ralph W. Bares ad Earl Youg, Ro Clapp, Ree McSwai, Betsy Vestal, Kare Asbury, Lois Hoots, Robi Brittai, Cythia Garriso, Ly Blake, Delilah Cook, Bob Elliso; Cliical Ceters Bowma Gray School of Medicie of Wake Forest Uiversity: Drs. David Lef kowitz (Pricipal Ivestigator), Philip R. Aroso, Richard Mario ad Cathy Nu, Kim Dameworth, Diae Combs, Steve Meads, Mitzie Spaihour, Kathlee Bradham; Uiversity of Iowa College of Medicie: Drs. Jose Biller (Pricipal Ivestigator), Joh Corso, Thomas Farrell, Helmut Schrott, Maleah Grover-McKay, Betsy B. Love, ad Lida Bea, Joh Adams, Jr., Edwi Miller, Kathy Hederso, Richard Murphy, Paul Pember, Elle Swaso, Nacy Jese; Uiversity of Ketucky Medical Ceter: Drs. Byro Youg, Robert Dempsey, Louise Diaa, Athoy DeMaria, Jea Amrie ad Lida Rice, Ruthie Sadler, Breda Brudage, Jerry Sherrow, Vicky Gatz, Debra Latham, Kay Holt; Uiversity of Teessee, Memphis: Drs. William B. Applegate, William Cushma, Stephe Miller, Philip Furr, ad Laretha Goodwi, Nacy Miles, Evely Clark, Gleda Hayes, Pam Rickma, Teresa Glaser, Amy Brewer, Judy Radle, Kim Curry, Susa Bills, Lisa Aderso, Regia Hagood, Michael Mosby, Jill Valesky, Jay Mitchell. Refereces 1. Gostomzyk JG, Heller WD, Gerhardt P, Lee PN, Keil U: B-sca ultrasoud examiatio of the carotid arteries withi a represetative populatio (MONICA Project Augsburg). Kli Wocheschr 1988;66(suppl XI): The ARIC Ivestigators: The Atherosclerosis Risk i Commuities (ARIC) study: Desig ad objectives. Am J Epidemiol 1989; 129: Fried LP, Borhai NO, Eright P, Furberg CD, Gardi JM, Kromal RA, Kuller LH, Maolio TA, Middlemark MB, Neuma A, O'Leary DH, Psaty B, Rautaharju P, Tracy RP, Weiler PG, for the CHS Collaborative Research Group: The Cardiovascular Health Study: Desig ad ratioale. A Epidemiol 1991;l: Saloe R, Saloe JT: Progressio of carotid atherosclerosis ad its determiats: A populatio-based ultrasoography study. Atherosclerosis 1990;81: Crouse JR, Harpold GH, Kahl FR, Toole JF, McKiey WM: Evaluatio of a scorig system for extracraial carotid atherosclerosis extet with B-mode ultrasoud. Stroke 1986;17: O'Leary DH, Brya FA, Goodiso MW, Rifki MD, Gramiak R, Ball M, Bod MG, Du RA, Goldberg BB, Toole JF, Wheeler HG, Gustafso NF, Ekholm S, Raies JK: Measuremet variability of carotid atherosclerosis: Real-time (B-mode) ultrasoography ad agiography. Stroke 1987;18: Poli A, Tremoli E, Colombo A, Sirtori M, Pigoli P, Paoletti R: Ultrasoographic measuremet of the commo carotid artery wall thickess i hypercholesterolemic patiets. Atherosclerosis 1988;70: Pigoli P, Tremoli E, Poli A, Oreste P, Paoletti R: Itimal plus medial thickess of the arterial wall: A direct measuremet with ultrasoic imagig. Circulatio 1986;74: Pigoli P: Ultrasoic evaluatio of arterial itima ad media thickess: Developmet ad validatio of methodology, i Glagov S, Newma WP, Schaffer S (eds): Pathobiology of the Huma Atherosclerotic Plaque. New York, Spriger-Verlag New York, Ic, 1989, pp The ACAPS Group: Ratioale ad desig for the Asymptomatic Carotid Artery Plaque Study (ACAPS). Cotrolled Cli Trials (i press) 11. Bod MG, Bares RW, Riley WA, Wilmoth SK: Quatitative high resolutio ultrasoography of carotid arteries, i Crepaldi G, Gotto AM, Mazato E, Daggio G (eds): Atherosclerosis VIII. New York, Elsevier Sciece Publishig Co, Ic, 1989, pp Bod MG, Bares RW, Riley WA, Wilmoth SK, Chambless LE, Howard G, Owes B: High resolutio B-mode ultrasoud scaig methods i the Atherosclerosis Risk i Commuities (ARIC) study. / Neuroimagig 1991;l: Riley WA, Bares RW, Bod MG, Evas G, Chambless LE, Heiss G: High resolutio B-mode ultrasoud readig methods i the Atherosclerosis Risk i Commuities (ARIC) study. / Neuroimagig 1991;1: Bod MG, Stricklad HL, Wilmoth SK, Safrit A, Phillips R, Szostak L: Itervetioal cliical trials usig oivasive ultrasoud edpoits: The Multiceter Isradipie/Diuretic Atherosclerosis Study. J Cardiovasc Pharmacol 1990;15(suppl l):s30-s Bod MG, Wilmoth SK, Evevold GL, Stricklad HL: Detectio ad moitorig of asymptomatic atherosclerosis i cliical trials. AmJMed 1989;86(suppl 4A): Glagov S, Weiseberg E, Zaris CK, Stakuavicius R, Kolettis GJ: Compesatory elargemet of huma atherosclerotic coroary arteries. N Egl J Med 1987;316: Armstrog ML, Mega MB, Heistad DD: Adaptive resposes of the artery wall as huma atherosclerosis develops, i Glagov S, Newma W, Schaffer S (eds): Pathobiology of the Huma Atherosclerotic Plaque. New York, Spriger-Verlag New York, Ic, 1989, pp