대한내과학회지 : 제 78 권제 4 호 2010 원저 09-281 선별검사목적으로시행된관상동맥 CT의석회수치에따른임상경과관찰 울산대학교의과대학서울아산병원 1 심장병센터, 2 건강증진센터, 3 심장내과, 4 영상의학과정인현 1,2 김정순 1,2 남효정 1,2 김희성 2 김홍규 2 박덕우 1,3 이승환 1,3 김영학 1,3 이철환 1,3 김재중 1,3 박성욱 1,3 박승정 1,3 강준원 4 Clinical outcomes according to coronary calcium scores in asymptomatic individuals undergoing coronary CT angiography In Hyun Jung, M.D. 1,2, Jeong Soon Kim, M.D. 1,2, Hyo-Jung Nam, M.D. 1,2, Hee Sung Kim, R.N. 2, Hong Kyu Kim, M.D. 2, Duk-Woo Park, M.D. 1,3, Seung-Whan Lee, M.D. 1,3, Young-Hak Kim, M.D. 1,3, Cheol Whan Lee, M.D. 1,3, Jae-Joong Kim, M.D. 1,3, Seong-Wook Park, M.D. 1,3, Seung-Jung Park, M.D. 1,3, and Jun-Won Kang, M.D. 4 1 Asan Heart Institute, 2 Health Promotion Center, Departments of 3 Internal Medicine, and 4 Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Background/Aims: In general, multidetector computed tomography (MDCT) is not recommended as a screening tool for asymptomatic individuals. However, the programs for general health evaluation at several hospitals in Korea include MDCT to detect cardiac disease. The objectives of this study were to evaluate the clinical outcomes of asymptomatic individuals according to the coronary artery calcium score (CACS) obtained from screening MDCT and to assess the eligibility of risk stratification in the NCEP-ATP III guidelines for predicting a significant stenosis on MDCT. Methods: We reviewed the medical records of 845 asymptomatic subjects (age 53±9 years, 67% men) who underwent MDCT as part of a general health evaluation at Asan Medical Center, Seoul, Korea, from January to December 2008. Results: Atherosclerotic plaques were identified in 332 (39.3%) subjects. Sixty (7.1%) individuals had significant stenosis ( 50% diameter stenosis). The prevalence of significant stenosis was higher in the group that had more than a 10% risk of coronary heart disease (CHD) at 10 years (p<0.05). Among the patients with occult coronary artery disease (CAD), 28 received coronary angiography, which resulted in 20 revascularizations (17 percutaneous interventions and three bypass surgeries) and eight medical treatments. In patients with significant narrowing, the CACS cutoff value for predicting coronary revascularization was 111.0 (AUC=0.87, 95% confidence interval; 0.76~0.97; sensitivity 80.0%, specificity 92.1%). Conclusions: According to the NCEP-ATP III guidelines, the prevalence of occult CAD on MDCT was significantly higher in the group with a 10% or higher risk for CHD at 10 years. A CACS 110 was associated with a significantly higher rate of coronary revascularization in asymptomatic patients with significant stenosis on MDCT. (Korean J Med 78:466-476, 2010) Key Words: Coronary disease; Tomography, spiral computed; Myocardial revascularization Received: 2009. 9. 9 Accepted: 2009. 12. 7 Correspondence to Hyo-Jung Nam, M.D., Asan Heart Institute, Health Promotion Center, Asan Medcal Center, 388-1 Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea E-mail: saveheart@freechal.com - 466 -
- In Hyun Jung, et al. Clinical outcome in asymptomatic individuals undergoing coronary CT angiography - 서론동맥경화에의한관상동맥질환은선진국에서성인사망률을높이는주요한원인이다 1). 우리나라에서도식생활문화의서구화와고령화로인해심혈관계질환의유병률과사망률이증가하고있는추세다. 한편 CT 기술의발달로다검출기 CT (multi-detector computed tomography, MDCT) 를이용한관상동맥 CT 혈관촬영검사가관상동맥을진단하는새로운검사방법으로대두되었다. 이미 1998년에 4절편 MDCT 가소개된이후, 2001년에 16 절편 MDCT 가등장하였으나시간해상도와공간해상도에관련된문제점들로인해관상동맥질환을평가하는데있어서많은제한점을가지고있었다. 최근들어널리사용되고있는 64절편 MDCT 는좀더빠른갠트리회전속도를갖추고있으며, 증가된검출기수로이러한제한점을크게향상시킬수있었다 2). 특히최근 64절편 MDCT 를이용한몇몇연구들에서관상동맥질환을진단하는데있어서비교적민감도와특이도가우수하며, 매우높은음성예측도를가지고있는검사로보고되고있다 3-6). 하지만고식적혈관조영술에비해비침습적인방법이라는큰장점때문에선별검사목적으로 MDCT 를사용하는것에대한논란이있음에도불구하고우리나라의경우많은대형병원에서건강검진프로그램의일환으로다른심장정밀검사들과함께 MDCT 가포함되어있다 7,8). 이로인해무증상환자에서잠재된관상동맥질환 (occult coronary artery disease) 이드물지않게발견된다. 그러나이러한선별검사목적으로시행된 MDCT 의임상적평가에대한연구결과는적다. 특히어떤환자군에서 MDCT 상유의한협착이많이발견되는지그리고유의한협착이의심될때, 실제로어떤환자군에서경피적관동맥성형술이나관동맥우회로수술까지받게되는지에대한연구는아직없었다. 한편전자선컴퓨터단층촬영 (electron-beam computed tomography, EBCT) 등을이용해측정한관상동맥석회화점수 (coronary artery calcium score, CACS) 가관상동맥의동맥경화반의총량과비례하고, 심혈관사건발생률과의관련성이비교적좋다는여러연구결과들이이미최근 10여년동안일관성있게발표되었다 9-12). 이에저자들은선별검사목적으로시행된 MDCT 상유의하게관상동맥협착을보이는환자의유병률을조사하고, NCEP-ATP III 지침에의한 10년관상동맥질환위험도에따라분류하였을때어떤집단에서 MDCT 상유의한협착이많 이관찰되는지알아보고자하였다. 또한 Receiver Operating Characteristic (ROC) 곡선을이용하여유의한관상동맥협착을보였던환자들중얼마이상의 CACS 값을갖는환자군에서경피적관동맥성형술또는관상동맥우회로수술을받게될가능성이높은지를알아보고자하였다. 대상및방법 1. 연구대상 2008년 1월 2일부터 2008년 12월 31일까지서울아산병원건강증진센터에내원하여건강검진을목적으로 64-slice MDCT 를이용한관상동맥 CT 촬영을시행한무증상수진자를대상으로후향적으로분석하였다. 검진을받기에앞서문진표를작성할때연구목적으로의무기록을열람하는것에동의하는지여부를서면으로구하였으며, 이에동의한대상자들만을연구에포함하였다. 흉통이있었거나관동맥성형술또는관상동맥우회로수술을받은환자, 뇌졸중의과거력이있는환자, 지질강하제를복용중인환자, 인슐린주사치료중인당뇨병환자, 나이가 30세미만, 75세이상인경우는제외하였으며, 최종 845명의무증상수진자가분석에포함되었다. 2. 연구방법 1) 위험인자평가본원건강증진센터에내원하는모든수진자에서흉통또는동등한증상이있었는지설문조사를통해확인하였다. 심근경색, 협심증, 고혈압, 뇌경색, 당뇨병을포함한과거병력, 최근약제복용력, 조기관상동맥질환및뇌졸중에대한가족력여부를설문지 (self-reported questionnaire) 를통해조사하였다. 건강증진센터방문시체중, 키, 허리둘레, 혈압을측정하였으며, 총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤 [high density lipoprotein (HDL)-cholesterol], 저밀도지단백콜레스테롤 [low density lipoprotein (LDL)-cholesterol], Apolipoprotein-A1, Apolipoprotein-B, homocysteine, high sensitivity C-reactive protein (hs-crp), 당화혈색소, 공복혈당, 혈중인슐린을 12시간금식상태에서채혈하여측정하였다. 고혈압은기존병력이있거나측정혈압이수축기혈압 140 mmhg 이상또는이완기혈압 90 mmhg 이상인경우로당뇨는 ADA (American Diabtes Association) 의진단기준에따라공복혈당이 126 mg/dl 이상이거나현재혈당강하제를복용중인경우로정의하였다. National Cholesterol Education Program - 467 -
- 대한내과학회지 : 제 78 권제 4 호통권제 596 호 2010 - Guideline에따라총콜레스테롤 240 mg/dl 또는저밀도지단백콜레스테롤 160 mg/dl인경우고지혈증으로분류하였다. 대상환자는 NCEP-ATP III 지침에의해계산된 10-year risk assessment tool (http://hp2010.nhlbihin.net/atpiii/riskcalc.htm) 을사용하였고, 이에따라저위험군 ( 위험인자 0~1개 ), 중등도위험군 ( 위험인자 2개이상, 10년관상동맥질환위험 <10%), 중등고위험군 ( 위험인자 2개이상, 10년관상동맥질환위험 10% 이상 20% 미만 ), 고위험군 ( 위험인자 2개이상, 10년관상동맥질환위험 >20%) 으로분류하였다 8,13). 2) 심근부하검사건강증진센터에내원하는수진자들중특정프로그램을선택한경우에는특별한금기가있는경우를제외하고는운동부하검사를받도록되어있으며, 선택된거의모든수진자에서시행하였다. 그러나무릎관절에퇴행성관절염이심하거나, 인공관절수술을받은환자와같이보행이나달리기가어려워충분한심장부하가이루어지지않을것으로판단되는환자또는기저심전도상완전좌각차단을보이는경우와같이검사판독이어려운경우에대하여는선택적으로 Tl-201 3 mci 를이용한심근관류 SPECT 검사를시행하였으며, pharmacological stress test 방법으로써 adenosine (140 µg/kg/min) 을사용하였다. 운동부하검사는 Bruce Protocol에따라진행하였다. 3) MDCT 검사 64-slice MDCT scanner VCT XT (General Electric, Milwakee, WI) 를이용하였으며, 관상동맥조영을위해사용되는표준 protocol (64 0.625 mm slice collimation, 350 msec rotation time, 120 kv tube voltage, 500~800 ma tube current according to patient body habitus) 에따라영상을획득하였다. 조영제로 400 mg/ml iodine 농도의조영제 (Iomeron 400, Bracco, Italy) 을초당 4 ml로총 80 ml를정주한후같은속도로생리식염수 50 ml를정주하였다. 영상획득시함께기록된심박수에따라분당 60회미만이면전향적심전도동조화법으로이상이면후향적심전도동조화법을이용하여획득하였고, 심박수가분당 75회를기준으로미만은 monosegment, 이상은 multi-segment algorithm을이용하여이완중기영상을재구성하였다. 심장 CT 검사의평균유효선량 (effective dose) 은 4.7±1.6 msv 였다. MDCT 촬영최소 4시간전에금식을하였고, 카페인등을 섭취하지않았다. 이전에베타차단제를복용하지않던환자에서심박동수가 65회 / 분이상인경우 atenolol 25~75 mg을 MDCT 촬영 1시간전에복용하여심박수를 65회 / 분이하로유지하려하였다. 검사전에심전도검사를하고심박동수와혈압을검사 1시간전, 30분전, 5분전에각각측정하였다. 니트로글리세린설하정 0.6 mg을 MDCT 촬영 1분전에투여하였다. 전촬영기간에걸쳐심전도를모니터링하였다. 조영제주입을위하여우측팔에 18~20 gauge의정맥도관을삽입하였다. 스캔을시행하는동안환자는약 8~10초간최대흡기를유지하였고, 참을수있는시간을늘리기위해필요한경우산소를공급하였다. 4) CT 판독모든심장 CT 영상은임상정보없이동일한연구자에의해분석되었다. 관상동맥협착은상용화된 workstation (Advantage Workstation, General Electric, Milwakee, WI) 을이용하여 1 mm 간격으로영상을재구성하여분석하였다. 유의한협착은 multi-planar reconstruction 영상이나 maximum intensity projection 영상에서내경이 50% 이상좁아졌을때로정의하였다. 동맥경화반은혈관내강및심막주변조직과는명확히구별되며, 혈관내강안또는그에인접해있는 1 mm 2 이상의구조물로정의하였다. 동맥경화반내면적대비석회화된조직이 50% 이상을차지할경우석회화경화반 (calcified plaque, density >130 HU) 으로, 50% 미만을차지할경우는혼재된경화반 (mixed plaque) 으로그리고석회화조직이관찰되지않을경우를비석회화경화반 (noncalcified plaque) 으로분류하였다 14). CACS는 Agatston 등 15) 에의해발표된방법에따라측정하였고, CACS에따라 0, 0.1~10, 10~100, 100.1~400, 400 이상의 5개군으로분류하였다. 5) Coronary angiogram MDCT 상관상동맥에유의한협착이관찰되고심근부하검사에서도유의한결과를보이는경우는관상동맥조영검사를진행하였다. 그러나심근부하검사에서음성이나온경우라하더라도 MDCT 상주관상동맥의근위부에유의한협착이보이는경우는혈관조영검사를시행하였다. 혈관조영검사중필요한경우에는혈관내강초음파검사 (Intravascular ultrasound, IVUS) 를시행하기도하였다. 혈관조영검사결과후주치의의판단에따라경피적관동맥성형술이나관상동맥우회로수술또는약물치료여부를결정하였다. - 468 -
- 정인현외 12 인. 선별검사목적의관상동맥 CT 의임상경과 - Table 1. Baseline characteristics Total number of patients (n) Total (845) Male (564) Female (281) Age (years) 53.5±9.0 52.8±9.0 * 54.9±9.0 Body mass index (kg/m 2 ) 24.9±3.4 25.5±3.2 * 23.6±3.3 Waist circumference (cm) 85.7±12.5 87.9±13.3 * 81.1±9.1 Current smoker 215 (25.4%) 205 (24.2%) * 10 (1.2%) SBP (mmhg) 114.7±12.6 116.5±11.5 * 111.2±14.0 DBP (mmhg) 70.9±10.0 72.9±9.4 * 66.7±10.1 Hypertension 244 (28.9%) 173 (20.5%) 71 (8.4%) Diabetes 92 (10.9%) 75 (8.9%) * 17 (2.0%) Hypercholesterolemia 218 (25.8%) 135 (16.0%) 83 (9.8%) Total Cholesterol (mg/dl) 200.0±37.5 196.9±34.6 * 206.2±42.2 Triglycerides (mg/dl) 140.1±124.7 153.8±139.7 * 112.5±80.6 HDL cholesterol (mg/dl) 53.9±13.0 51.0±11.7 * 59.8±13.6 LDL cholesterol (mg/dl) 127.6±32.0 125.9±29.5 * 130.8±36.4 Apolipoprotein A1 (mg/dl) 146.5±23.7 142.2±21.7 * 153.3±25.3 Apolipoprotein B (mg/dl) 91.6±23.4 92.9±22.2 89.5±25.1 Homocysteine (umol/l) 13.2±3.6 14.3±3.5 * 11.4±2.9 Hs CRP (mg/dl) 0.12±0.18 0.12±0.17 0.11±0.19 Fasting serum glucose (mg/dl) 104.3±20.4 106.9±23.0 * 99.0±12.2 HbA1c (%) 5.6±0.8 5.6±0.8 * 5.5±0.7 Insulin (uui/ml) 7.7±4.9 8.0±4.9 * 7.1±4.7 BUN (mg/dl) 13.4±3.4 14.0±3.5 * 12.3±2.9 Serum creatinine (mg/dl) 0.9±0.2 0.95±0.13 * 0.71±0.10 Estimated GFR 79.0±7.2 79.3±7.0 78.1±7.4 Familial history of premature CHD 121 (14.3%) 82 (9.7%) 39 (4.6%) Familial history of stroke 112 (13.3%) 68 (8.0%) 44 (5.2%) Data are expressed as number (%) or mean±sd. *p<0.05. SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; hs-crp, high sensitivity C-reactive protein; HbA1c, glycosylated hemoglobin; BUN, blood urea nitrogen; GFR, glomerular filtration rate; CHD, coronary heart disease. 6) 통계연속변수는평균 ± 표준편차로, 범주형변수는빈도 (%) 로표기하였다. 연속형변수는독립표본 t-검정, 범주형변수는 x 2 분석을이용하여통계적유의성을검정하였다. CACS 로경피적관동맥성형술및관상동맥우회로수술여부를층화 (stratification) 하는정도는 receiver operating characteristic (ROC) 곡선을이용하여분석하였으며, 민감도와특이도의합이최대가되는 CACS와그값의민감도및특이도를구하였다. CACS의 cutoff 수치가 MDCT상유의한협착을보이는환자에서실제로경피적관동맥성형술이나관상동맥우회로수술을받은환자군과그렇지않은환자군을구별하는 데있어독립적영향을미치는가는로지스틱회귀분석으로평가하였다. 통계분석은 SPSS 프로그램 (SPSS 12 for Windows, SPSS Incorporation, Chicago, IL, USA) 을사용하였으며 p<0.05 를유의한것으로간주하였다. 결과 1. 임상적특징대상군은총 845명으로남자가 564명 (66.7%) 이었고, 연령분포는 53.5±9.0세였다. 고혈압및당뇨병의유병률은 244명 (28.9%) 과 92명 (10.9%) 이었으며, 체질량지수는 24.9±3.4 kg/m 2-469 -
- The Korean Journal of Medicine: Vol. 78, No. 4, 2010 - Table 2. Coronary CT angiography analysis Characteristic, n (%) Total (n=845) Male (n=564) Female (n=281) Any plaque 332 248 * 84 Significant stenosis 60 48 * 12 Number of stenosed vessels 1-vessel 42 35 7 2-vessel 14 10 4 3-vessel 4 3 1 No plaque 513 316 * 197 Noncalcified plaques only 56 39 17 Mixed plaques 88 69 19 Calcified plaques 188 140 48 CACS 41.5±131.2 48.9±144.9 * 26.6±96.6 CACS, coronary artery calcium score. *p<0.05. Luminal diameter stenosis 50% Diseased vessel with significant luminal diameter stenosis. Table 3. Frequency of events in each group categorized by coronary artery calcium score CACS Total Significant stenosis CAG PCI/CABG 0 547 6 4 3/0 0.1~10 74 2 1 1/0 10.1~100 141 11 2 0/0 100.1~400 56 18 7 5/0 >400 27 23 14 8/3 CACS, coronary artery calcium score; CAG, coronary angiography; PCI, percutaneous coronary intervention; CABG, coronary arterial bypass graft. 였다. 총콜레스테롤수치는 200.0±37.5 mg/dl 였다 ( 표 1). 2. 관상동맥 CT 조영검사분석심장 CT 검사결과관상동맥의동맥경화반이보였던환자는 332명 (39.3%) 이었고, 석회화된경화반이 188명, 석회화를보이지않는비석회화경화반이 56명, 혼재한경화반이 88명에서관찰되었다. 이중 50% 이상의유의한협착을보이는환자는 60명 (7.1%) 이었다. 동맥경화반의유무나유의한협착의유병률은여자에서보다남자에서유의하게높았다. 또한 CACS도남자가 48.9±144.9로여자 26.6±96.6보다의미있게높았다 ( 표 2). 3. 임상경과관찰건강검진목적으로관상동맥 CT 조영검사를시행받은무증상환자는총 845명이었으며, 이가운데 60명이 50% 이상의유의한협착으로진단되었다. 이중 55명이운동부하검사나심장관류스캔검사를받았으며, 운동부하검사에서 9명, 심장관류검사에서 1명, 총 10명에서양성소견을보였다. 운동부하검사나심장관류스캔검사에서음성소견을보였더라도 MDCT 검사상주관상동맥의근위부에협착을보인 18명과양성소견을보인 10명을포함하여 28명이관상동맥조영술을시행받았다. 관상동맥조영검사의결과에따라 17명이경피적관동맥성형술, 3명은관상동맥우회로수술을받았다. 나머지 8명은적극적인예방적약물치료를하면서외래에서추적관찰하기로하였다 ( 그림 1). - 470 -
- In Hyun Jung, et al. Clinical outcome in asymptomatic individuals undergoing coronary CT angiography - Figure 1. Clinical progress of enrolled patients based on the coronary CT angiography results. 4. 관동맥협착을구별하는데있어서 CACS 의역할및각위험군에따른유병률비교 Figure 2. Receiver operating characteristics curve for the prevalence of significant stenosis on coronary computed tomographic angiography. Significant stenosis was defined as more than 50% luminal narrowing on multidetector computed tomography. NCEP-ATP III risk stratification (AUC, 0.72; 95% confidence interval, 0.65~0.78). CACS, CACS risk stratification (AUC, 0.89; 95% confidence interval, 0.84~0.95). AUC, area under the curve, NCEP-ATP, National Cholesterol Education Program- Adult Treatment Panel, CACS, Coronary artery calcium score. MDCT 상유의한협착을구별하는데있어서 NCEP-ATP III 지침에따른 10년관상동맥질환위험과 CACS의 receiver operating characteristics (ROC) 곡선의 area under the curve (AUC) 를비교했을때, CACS가 0.89 (95% 신뢰구간 : 0.84~ 0.95) 로 NCEP-ATP III 지침 0.72 (95% 신뢰구간 : 0.65~0.78) 보다높은비율로유의한협착을구별하였다 ( 그림 2). 또한 NCEP-ATP III 지침에따라분류한각위험군에서 10 년관상동맥질환위험이 10% 이상인군이 10% 미만인군에비해 MDCT 상 50% 이상관상동맥의유의한협착이발견된비율이의미있게높았다 ( 그림 3). 5. MDCT 상유의한협착을보이는환자와중재시술이나우회로수술을받은환자에서 CACS 의분포전체대상군에서 CACS가 0인환자수는 547명이었고, 이중 MDCT 상유의한협착을보인경우는 6명이었으며, 이가운데 3명이관상동맥조영술후에관상동맥중재시술을받았다. 400 이상인경우는모두 27명이었고, 이들중 8명이중재 - 471 -
- 대한내과학회지 : 제 78 권제 4 호통권제 596 호 2010 - Figure 3. Prevalence of significant stenosis in each risk group. Individuals were categorized into risk groups according to the NCEP-ATP III guidelines. Significant stenosis was defined as more than 50% luminal narrowing on multidetector computed tomography. NCEP-ATP, National Cholesterol Education Program- Adult Treatment Panel; NS, not statistically significant. 시술을받았고, 3 명은관상동맥우회로수술을받았다 ( 표 3). 6. 중재시술이나우회로수술을받은환자에서 CACS 의 cutoff값 ROC 곡선을이용하여관상동맥의유의한협착이관찰될때실제로중재시술이나수술까지받은환자에서 CACS의 area under the curve는 0.87 (95% 신뢰구간 : 0.76~0.98) 로 cutoff 값은 111.0 ( 민감도 80%, 특이도 92%) 이었다 ( 그림 4). 한편 MDCT 상유의한협착을보인환자들에서이분변수로분류한위험인자와 ROC curve 로구한 CACS 수치를기준으로로지스틱회귀분석을하였으며, CACS 110은중재시술및수술을받는것과관련이있는독립적인자였다 ( 표 4). 고 본연구는건강검진목적으로관상동맥 CT 조영검사를받은무증상수진자를대상으로이들의관상동맥석회수치에따른임상경과를관찰하였다. MDCT 상관상동맥의유의한협착을갖는환자의유병률은 Framingham risk score로평가된 10년심혈관계합병증의위험도가 10% 이상인중등고위험군및고위험군에서 10% 미만인군에비해유의하게높 찰 A CACS Sensitivity 1-Specificity 103.0 108.5 111.0 112.5 115.5 0.800 0.800 0.800 0.750 0.750 0.082 0.081 0.079 0.079 0.078 Figure 4. Receiver operating characteristics curve for the prevalence of PCI or CABG. 았다. 또한 MDCT 상 50% 이상의관상동맥협착을보이면서 CACS가 110 이상인군의경우는향후에경피적관상동맥성형술이나관상동맥우회로수술을받게될가능성이의미있게높았다. MDCT 는관상동맥질환을진단하는목적으로최근에많이사용되고있다. 그러나현재미국심장학회 (ACC/AHA) 지침에따르면무증상환자에서선별검사를목적으로 MDCT 를사용하는것은추천되지않는다 8). 가장큰이유로는불필요한의료비용의상승과방사선피폭으로인한암발생위험도증가등의문제를들수있다. 건강검진목적으로시행되는검사로서 MDCT 의가장큰제한점은무엇보다도방사선조사에의한암발생위험도증가라는문제이며, 이는매우민감한사안이다. 이미, FDA (The Food and Drug Administration) 에서 10 msv CT로검사를받은환자 2,000명당한명정도의암발병률이예측된다는보고를한바있다 16). 그러나 Husmann 등 17) 은저용량관상동맥 CT 조영술로이러한문제를어느정도극복할수있다고보고하였다. 특히이연구에서저자들은평균 1.1~3.0 msv 정도의방사선량만으로도진단에어려움이없을정도의양질의영상을얻을수있 - 472 -
- 정인현외 12 인. 선별검사목적의관상동맥 CT 의임상경과 - Table 4. Results of logistic regression analysis to assess the independent influence of CACS on revascularization Parameter Odds ratio 95% CI p Male gender 0.6 0.2~1.9 0.356 Age > 60 years 1.4 0.4~4.2 0.582 Hypertension 1.2 0.4~3.5 0.704 Current smoker 0.6 0.2~2.1 0.447 Dyslipidemia 0.5 0.2~1.7 0.297 CACS 110 28.8 8.9~92.9 <0.001 CI, confidence interval; CACS, coronary artery calcium score. 었다고보고하였다. Raff 등 18) 은방사선조사량을줄이는기법 (radiation dose-reduction technique) 의사용전후를비교하였으며, 영상의질에유의한차이없이방사선피폭량을 53.3% 나줄일수있었다고보고하였다. 본연구에포함된수진자들에게적용된방사선조사량은평균 4.7±1.6 msv 이었다. 이러한결과는 MDCT 를이용하여발표된국내다른연구들보다도낮았으며, 대상군의유의한협착의유병률에있어서는큰차이가없었다. 또한선별검사목적으로 MDCT 를사용함에있어서이러한득실을고려하여, 어느정도의심혈관질환의위험도를갖는군을대상으로하는것이유용한지를제시할수있는객관적인자료가필요하다. 임상적심혈관질환이나관상동맥질환이없는사람에서향후심혈관질환의위험도평가하고위험인자관리를위해이용되는지표로서미국의 Framingham risk score와유럽의 SCORE system이알려져있으나, Framingham risk score가비교적대규모집단을대상으로장기적인관찰을통해그적용성이잘확립되어있다 13,19). 그러나이와같은위험도의산출방식은특정인구집단의역학연구를바탕으로만들어진것으로서다른인구집단에서관상동맥질환의발생을예측하는데있어서명확한한계가있다는것이여러연구를통해지적되어왔다. 또한최근 Framingham risk score를비롯한전통적인위험도산출방식에대해고위험군및저위험군의판단에는유용하지만, 대부분의 heart attack이발생하는중등도위험집단에대해서는그판별력을크게신뢰할수없다는주장이제기되고있다. 하지만간단한병력청취와콜레스테롤수치만으로심혈관계질환의위험도를비교적쉽게예측할수있다는장점때문에임상에서많이쓰이고있다 20-22). 본연구에서는 NCEP-ATP III 지침의위험도에따라 4군으로분류하였을때 MDCT 상관상동맥에유의한협착의유병률이중등고위험군, 고위험군에서각각 17.2%, 12.5% 로, 저위험군과중등위 험군 3.7%, 4.4% 에비해의미있게높았다. 따라서현재선별검사목적의 MDCT 시행에대하여는논란의여지가많은상황에서건강검진이잘발달되어있는우리나라의료환경의특수성을감안한다고하더라도 NCEP-ATP III 지침에따른위험도가 10% 미만인군에서는관상동맥질환에대한선별검사목적으로 MDCT 를사용하는것에대하여어느정도제한을두는것이바람직할것으로생각된다. 관상동맥석회수치는관상동맥의동맥경화반의총량과비례하고, 관상동맥의협착을예측하는지표가되며, 허혈성심장질환발생의독립적인위험인자가되는것으로알려져있다 11,12). CACS는이전에는전자선단층촬영기 (electron beam computed tomography) 를이용하여측정할수있었으나최근에는 CACS 측정뿐만아니라, 관상동맥의협착부위를구체적으로찾고진단하는데유용한 ECG gated multi-detector computed tomography (MDCT) 를많은의료기관에서갖추고있다. 최근 SHAPE guideline 23) 이발표되어관상동맥석회수치의중요성을더욱강조하였고, 국내에서도관상동맥석회수치의역할과그적응증을제시하기위한연구가있었다 3,5,6,24). 특히, 건강검진을받은수진자들을대상으로 NCEP- ATP III 지침과 SHAPE guideline을비교한한연구에서무증상관상동맥질환의유무를판별하는데있어서 SHAPE 지침이 NCEP-ATP III 지침보다 MDCT 소견에더잘부합되었다고하였다 8). 본연구에서 50% 이상의관상동맥협착을보이는환자를판별하는데있어서 CACS 가 NCEP-ATP III보다더우수함을보여주었다. 특히 MDCT 상유의한협착을보이는무증상환자에서 CACS가 110 이상인경우에는실제로경피적관동맥성형술이나관상동맥우회로수술이필요할가능성이높았다. 그러나이번연구에서유의한관상동맥협착을보인환자들 60명중 CACS가 10 이하로낮은경우가 8명 (13.3%) 이었으며, CACS가 0인환자도 6명 (10%) 이나되었다. 또한이들중 3명 (5%) 이경피적관동맥성형술 - 473 -
- The Korean Journal of Medicine: Vol. 78, No. 4, 2010 - 을받았다. Hennenman 등 25) 은급성관동맥증후군이의심되는환자 40명을대상으로한연구에서급성관동맥증후군의경우 MDCT 상비석회화죽상판을갖는경우가유의하게많았으며, 관상동맥의석회화가없다고해서유의한협착이나동맥경화가없다고할수는없다. 즉, 관상동맥의석회화된죽상판은동맥경화의더진행되고안정화된형태로볼수있으며, 비석회화죽상판은동맥경화의초기단계에서볼수있는소견으로단순히 CACS 만으로동맥경화의중증도를진단하는것은곤란하다고하겠다. 또한무증상환자에서경피적관동맥성형술이나관상동맥우회로수술과같은침습적관상동맥재개통술여부를결정함에있어서현재의지침은심근부하검사결과에서유의한심근허혈유무를확인하거나삼혈관질환 (three vessel disease) 이나좌주관부협착 (left main disease) 과같은고위험군을확인하는것으로결정되며, 단순히관동맥석회화수치만을가지고판단할수는없다. 특히지금까지의연구에서관상동맥성형술이안정형협심증환자에서생존율을증가시킬수있다는증거는없다 26,27). 따라서잠재된관상동맥질환 (occult coronary arterial disease) 의경과관찰에대한연구를위해서는보다대규모의장기간경과관찰을조사하는연구가필요하며모든무증상환자에서이와같은결론을확대적용하기에는무리가있을것으로생각된다. 이번연구는후향적연구로 MDCT 를통해관찰된유의한관상동맥협착소견을보이는환자에서 CACS에따른임상경과를관찰하였다. 그러나단일기관의건강검진환자를대상으로하여일반적으로소규모의임상연구가갖는제한점을가지고있다고보아야하겠다. 또한설문형식을통해얻어진관상동맥질환에대한위험인자및병력에대한정보취합역시이연구의정확성을떨어뜨리는요소로작용했을수있다. 특히 MDCT 상 50% 이상의협착을갖는모든환자들에게관상동맥조영술을시행한것이아니고심근부하검사에서양성결과를보이거나주관상동맥의근위부협착을보이는환자들에게시행했다는점에서선택비뚤림 (selection bias) 의가능성이있다. 무엇보다도무증상환자군을대상으로하였기때문에실제로관상동맥조영술까지진행된증례가연구에포함된환자수에비해상대적으로적고, 따라서중재시술까지이어지는예도적을수밖에없었다. 그러나본연구는무증상환자를대상으로시행한 MDCT 에서유의한협착이관찰되었을때이에대한임상적인해석을하는데도움을줄것으로기대된다. 결론적으로미국이나유럽의다른나라들과는달리건강 검진의꾸준한수요가있고, 건강검진이잘발달되어있는우리나라의료환경의특수성을감안하더라도, NCEP-ATP III 지침에따른관상동맥질환의위험도가 10% 미만인군에서는유의한협착이발견될가능성이낮으므로선별검사목적으로 MDCT 를사용하는것은가급적자제하는것이좋을것으로생각된다. 또한 MDCT 상유의한협착이의심되고 CACS가 110 이상일때에는경피적관동맥성형술이나관상동맥우회수술과같은관상동맥재개통술을받게될가능성이의미있게높았다. 그러나이미보고된다른문헌들에서와마찬가지로비석회화동맥경화반의유의한협착도존재할수있으므로단순히 CACS 수치자체만으로해석하는것은피해야할것으로생각된다. 요약목적 : 최근많은연구에서 MDCT 가관상동맥질환을진단하는데있어서비교적민감도와특이도가우수하고, 높은음성예측도를가진검사로보고되고있다. 그러나무증상환자군에서 MDCT 상유의한협착이보일때어떤환자군에서경피적관동맥성형술이나관동맥우회로수술을받는가에대한임상경과를관찰한연구는아직없다. 이에저자들은선별검사목적으로 MDCT 를시행한무증상환자의관상동맥석회수치에따른임상경과를보고자하였으며, 선별검사목적의 MDCT 의무분별한사용을줄이기위해 NCEP-ATP III 지침에따라 10년관상동맥질환위험도를구분한각집단중어떤집단에서 MDCT 상유의한협착이많이관찰되는지알아보고자하였다. 방법 : 건강검진을목적으로서울아산병원건강증진센터에방문한 845명의의무기록과 MDCT 를후향적으로분석하였다. MDCT 상유의한협착은관상동맥내경이 50% 이상좁아진경우로정의하였고, 관상동맥질환위험도는 NCEP- ATP III 지침에의해계산된 10-year risk assessment tool (http://hp2010.nhlbihin.net/atpiii/riskcalc.htm) 을사용하였다. 침습적관상동맥조영술은심근부하검사가양성이거나심근부하검사가음성이라도 MDCT 상주관상동맥의근위부에유의한병변이있을때시행하였고, 관상동맥재개통술여부는관상동맥조영술후주치의의판단에의해결정되었다. 결과 : 총 332명 (39.3%) 에서동맥경화반이관찰되었으며이들가운데 60명 (7.1%) 은관상동맥의유의한협착을보였다. MDCT 상유의한협착을갖는환자의유병률은 NCEP- - 474 -
- In Hyun Jung, et al. Clinical outcome in asymptomatic individuals undergoing coronary CT angiography - ATP III 지침에따른위험도에따라구분하였을때, 10년심혈관계합병증의위험도가 10% 이상인군에서의미있게높았다. 유의한협착을보인환자들중 28명이관상동맥조영검사를받았으며, 17명은경피적관동맥성형술을받았고, 3 명은관상동맥우회로수술을받았다. ROC 곡선을이용하여 MDCT 상유의한협착을가진환자에서관상동맥재개통술 (revascularization) 을시행받은환자에대한 CACS의 cutoff 값은 111.0 (AUC=0.87, 95% confidence interval; 0.76~0.97, sensitivity 80.0%, specificity 92.1%) 이었다. 결론 : 현재선별검사목적의 MDCT 시행에대하여논란의여지가많은상황에서 NCEP-ATP III 지침에따른위험도가 10% 미만인군에대하여는관상동맥질환에대한선별검사목적으로 MDCT 를사용하는것은가급적제한하는것이바람직할것으로생각된다. 또한선별검사목적으로시행된 MDCT 상유의한협착이관찰되고 CACS가 110 이상일경우경피적관동맥성형술이나관상동맥우회수술과같은관상동맥재개통술을받게될가능성이의미있게높았다. 중심단어 : 관상동맥질환 ; 전산단층촬영술 ; 심근혈관재형성 REFERENCES 1) Beaglehole R. Global cardiovascular disease prevention: time to get serious. Lancet 358:661-663, 2001 2) Ko SM. Diagnostic accuracy of 64-slice multi-detector CT coronary angiography in the evaluation of coronary artery disease. Korean J Med 75:39-41, 2008 3) Choi EK, Choi SI, Rivera JJ, Nasir K, Chang SA, Chun EJ, Kim HK, Choi DJ, Blumenthal RS, Chang HJ. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol 52:357-365, 2008 4) Miler JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, Paul N, Clouse ME, Shapiro EP, Hoe J, Lardo AC, Bush DE, Roos A, Cox C, Brinker J, Lima JC. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 359:2324-2336, 2008 5) Namgung J, Choe HM, Kwon SU, Doh JH, Lee SY, Hur G, Lee WR. Diagnostic accuracy of 64-slice multidetector CT coronary angiography for the evaluation of coronary artery disease. Korean J Med 75:42-53, 2008 6) Cho YJ, Yoon YE, Kim JH, Park JB, Park HE, Lee WJ, Choi EK, Chun EJ, Choi SI, Choi DJ, Chang HJ. Comparison of primary prevention strategies for coronary heart disease in asymptomatic individuals: the national cholesterol education program adult treatment panel III guideline versus the screening for heart attack prevention and education guideline. Korean Circ J 38:483-490, 2008 7) Chang HJ, Choi SI. Era of multimodality imaging: where do we stand? Korean Circ J 36:717-722, 2006 8) Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE. Assessment of CAD by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114:1761-1791, 2006 9) Bielak LF, Rumberger JA, Sheedy PF, Schwartz RS, Peyser PA. Probabilistic model for prediction of angiographically defined obstructivecoronary artery disease using electron beam computed tomography calcium score strata. Circulation 102:380-385, 2000 10) Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P, Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 49:378-402, 2007 11) Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology 228:826-833, 2003 12) Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Callister TQ, Raggi P, Berman DS. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 49:1860-1870, 2007 13) National Cholesterol Education Program (NCEP-ATP III) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third Report of the National Cholesterol Education Program (NCEP-ATP III) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106:3143-3421, 2002 14) Leber AW, Becker A, Knez A, von Ziegler F, Sirol M, Nikolaou K, Ohnesorge B, Fayad ZA, Becker CR, Reiser M, Steinbeck G, Boekstegers P. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary - 475 -
- 대한내과학회지 : 제 78 권제 4 호통권제 596 호 2010 - system: a comparative study using intravascular ultrasound. J Am Coll Cardiol 47:672-677, 2006 15) Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827-832, 1990 16) Mieres JH, Shaw LJ, Arai A, Budoff MJ, Flamm SD, Hundley WG, Marwick TH, Mosca L, Patel AR, Quinones MA, Redberg RF, Taubert KA, Taylor AJ, Thomas GS, Wenger NK. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation 111:682-696, 2005 17) Husmann L, Valenta I, Gaemperli O, Adda O, Treyer V, Wyss CA, Veit-Haibach P, Tatsugami F, von Schulthess GK, Kaufmann PA. Feasibility of low-dose coronary CT angiography: first experience with prospective ECG-gating. Eur Heart J 29:191-197, 2008 18) Raff GL, Chinnaiyan KM, Share DA, Goraya TY, Kazerooni EA, Moscucci M, Gentry RE, Abidov A. Radiation dose from cardiac computed tomography before and after implementation of radiation dose-reduction techniques. JAMA 301:2340-2348, 2009 19) Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, De Baquer D, Ducimetiere P, Jousilahti P, Keil U, Njolstad I, Oqannov RG, Thomsen T, Tunstall-Pedoe H, Tverdal A, Wedel H, Whincup P, Wilhelmsen L, Graham IM. Estimation of ten year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 24:987-1003, 2003 20) Akosah KO, Schaper A, Cogbill C, Schoenfeld P. Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform? J Am Coll Cardiol 41:1475-1479, 2003 21) Nasir K, Michos ED, Blumenthal RS, Raggi P. Detection of high risk young adults and women by coronary calcium and National Cholesterol Education Program Panel III guidelines. J Am Coll Cardiol 46:1931-1936, 2005 22) Brindle P, Beswick A, Fahey T, Ebrahim S. Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review. Heart 92:1752-1759, 2006 23) Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D, Fayad Z, Budoff MJ, Rumberger J, Naqvi TZ, Shaw LJ, Faergeman O, Cohn J, Bahr R, Koenig W, Demirovic J, Arking D, Herrera VL, Badimon J, Goldstein JA, Rudy Y, Airaksinen J, Schwartz RS, Riley WA, Mendes RA, Douglas P, Shah PK. From vulnerable plaque to vulnerable patient: part III. executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 98:2H-15H, 2006 24) Kim MH, Kim JH, Byun SS, Hwan HY, Yang DM, Kim HS. Evaluation of atherosclerotic plaque inpatients without coronary artery calcification using multidetector row computed tomography: a preliminary report of 110 patients. J Korean Radiol Soc 58:29-37, 2008 25) Henneman MM, Schuijf JD, Pundziute G, van Werkhoven JM, van der Wall EE, Jukema JW, Bax JJ. Noninvasive evaluation with multislice computed tomography in suspected acute coronary syndrome. J Am Coll Caridol 52:216-222, 2008 26) Gibbons RJ, Abrams J, Chtterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB, Fihn SD, Fraker TD, Gardin JM, Gardin JM, O Rourke RA, Pasternak RC, Williams SV, Alpert JS, Antman EM, Hiratzka LF, Fuster V, Faxon DP, Gregoratos G, Jacobs AK, Smith SC Jr. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina-summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 107:149-158, 2003 27) Mann JM, Davies MJ. Vulnerable plaque: relation of characteristics to degree of stenosis in human coronary arteries. Circulation 94:928-931, 1996-476 -