대한내과학회지 : 제 71 권제 3 호 2006 안정형협심증과급성관상동맥증후군환자에서경동맥의재형성 경상대학교의과대학내과학교실 박정랑 권태정 강영란 박소라고진신 임성일 박성지 곽충환 황진용 =Abstract= Carotid artery remodeling in patients with acute coronary syndrome and chronic stable angina Jeong Rang Park, M.D., Tae Jung Kwon, M.D., Young Ran Kang, M.D., So Ra Park, M.D., Jin Sin Kho, M.D., Sung Il Im, M.D., Sung-Ji Park, M.D., Chung Hwan Kwak, M.D. and Jin Yong Hwang, M.D. Department of Internal Medicine, Gyeong-Sang National University College of Medicine, Jinju, Korea Background : Acute adaptive vascular remodeling occurs in active and unstable inflammatory plaques. It has been suggested that the adaptive coronary vascular remodeling, in patients with acute coronary syndrome (ACS), may be systemic and may show similar vascular remodeling in the carotid arteries. We investigated the ultrasonographic features of the common carotid artery (CCA) to determine whether the arterial expansive remodeling found in the coronary artery occurs in the carotid arteries of patients with ACS. Methods : We measured lumen diameter (LD), interadventitial diameter (IAD) and intima media thickness (IMT) using a B-mode ultrasound in both common carotid arteries in patients with ACS (N=74) and chronic stable angina (CSA) (N=31). Positive remodeling was arbitrarily defined as an IMTmax >1 mm and IAD >8 mm and negative remodeling as an IMTmax >1 mm and IAD <7 mm. Other values were defined as no remodeling Results : There were no significant differences in LD IAD and maximal IMT of the right CCA and the left CCA in comparisons between the ACS and the CSA patient groups. There were no differences for number of cases with no remodeling or differences in positive and negative remodeling in the right common carotid artery and left common carotid artery in comparisons between the ACS and CSA patient groups.. Presence of plaque in both common carotid arteries showed similar frequency in the ACS and CSA patient groups. The characteristics of carotid artery plaques were not different in the two groups. The remodeling index (IAD/LD) was correlated with IMTmax (right CCA r=0.797, p<0.001; left CCA r=0.860, p<0.001). Conclusions : The common carotid arterial structure of ACS patients was not different from that of CSA patients. Therefore, these results suggest that the expansive arterial remodeling, due to Received : 2005. 12. 15. Accepted : 2006. 2. 3. Correspondence to : Jin Yong Hwang, M.D. Department of Internal Medicine, Gyeongsang National University College of Medicine. #90 Chiram-dong, Jinju 660-702, Korea E-mail : jyhwang@nongae.gsnu.ac.kr - 266 -
-Jeong Rang Park, et al : Carotid artery remodeling in acute coronary syndrome and chronic stable angina - coronary inflammatory plaques, appears to take place locally rather than systemically.(korean J Med 71:266-275, 2006) Key Words : Acute coronary syndrome, Arterial remodeling, Carotid artery 서론과거에는동맥경화반이형성되면당연하게혈관의내경이좁아지는것으로만생각되어져왔다. 그러나동맥벽은딱딱한관이아니고혈역학적변화, 기계적인자극, 생화학적자극에따라모양을재형성할수있다는것이최근증명되어있다. 많은경우에동맥경화반에의해내강이좁아졌을때나동맥손상에의해신생내피비후가있을때혈관의외경이부분적으로나전체적으로커져서보상하는방향 (positive remodeling) 1, 2) 으로진행되지만, 때로는외경이오히려좁아져서내경의협착을조장하는경우 (negative remodeling) 3, 4) 도있다고한다. 심근경색증, 불안정형협심증, 심장돌연사를나타내는급성관상동맥증후군은동맥경화반의파열이나내피세포의탈락으로혈전이형성되어혈류가차단되거나거의차단되는경우에발생하는임상양상이다. 이런현상은관상동맥조영연구에의하면심한관상동맥협착을가지고있는환자에서보다비교적경도나중등도의협착이있는동맥경화반에서흔히관찰된다고한다 5, 6). 최근에혈관내초음파기를이용한관상동맥구조를관찰한연구에서는동맥경화반이파열되거나파열된주위에는보상적으로혈관이확장되어있는양성재형성과연관이있고, 흔히그부위에는동맥경화가없는부위가한쪽벽면을차지하는경우가많다고한다 7, 8). 이로인해양성재형성은활동적이고염증이진행하는동맥경화반에서흔히일어나기때문에혈관의내강을유지하려는보상적인측면도있지만한편으로는동맥경화반의구조를불안정하게만드는데기여하는것으로추측하고있다. 손쉽게측정할수있는고해상도의 B-mode 초음파가동맥벽에서동맥경화의변화를관찰하는데신뢰할만한영상검사로인정되면서부터관상동맥질환과경동맥구조와의상관성에대한연구가많이진행되고있다. 특히 Atherosclerosis Risk in Communities (ARIC) 연구 9) 에의하면동맥벽이약간두꺼워져있으면경동맥외경이 커지는양성재형성을보이지만매우심하게동맥벽이두꺼워져있으면오히려경동맥외경이감소하는음성재형성을보인다고한다. 시간의경과에따라관찰한연구에의하면동맥경화성비후와동맥외경의증가는직접적인상관관계가있고경동맥의동맥경화반의크기가급속하게증가하면동맥의확장이동반되고동맥경화반의크기가안정적으로변화가없으면동맥의전체구조는변화하지않는다고하였다 10, 11). 특히총경동맥의외경이관상동맥질환자에서정상대조군보다나이, 키와성별로교정하면약간커져있고, 내경은내중막두께 (intima media thickness) 가증가된사람에서약간커져있었으나관상동맥질환자나정상대조군이나아무런차이가없었다고한다 12). 그러나급성관상동맥증후군에서의관상동맥에서일어나는동맥의재형성변화가전신적으로다른혈관즉경동맥이나상지동맥에서같이일어나는지에대한연구는확정된연구가없고논란이있는실정이다 12, 13). 더구나급성관상동맥증후군환자의혈액에서염증성인자가증가되어있고관상동맥의불안정죽상반이다발성으로여러부위에존재한다는것이잘알려져있어관상동맥의재형성이전신적으로다른혈관에도일어난다는가설을검정하고자하였다. 이에저자는관상동맥질환이비슷한급성관상동맥증후군과안정형협심증환자에서경동맥과상지동맥구조의차이를관찰하여급성관상동맥증후군에서발생하는관상동맥의염증으로인한혈관재형성이신체의다른혈관에도발생하는가를알아보고자본연구를시행하였다. 대상및방법 1. 환자군본연구의대상환자는 2004년 1월부터 2005년 5월까지경상대학교병원에서관상동맥조영술을시행한 105 명이었고, 이중급성관상동맥증후군은허혈성흉통과함께 ST 분절의상승이나하강이 0.5 mm 이상혹은 T - 267 -
- 대한내과학회지 : 제 71 권제 3 호통권제 553 호 2006 - 파역전이 2개의전극이상에서관찰되었던환자이거나이와동반되어 troponin I가 0.2 ng/dl 이상상승한환자로 74명이었고, 만성안정형협심증환자는검사 2개월이내에임상적으로증상의변화가없었던환자 31명이었다. 본연구에서최근 6개월내에뇌혈관계사건이있었거나만성신부전 (creatinine >2.5 mg/dl) 이있거나과거에경동맥시술을받은경우나관상동맥조영에서고정된병변이없는이형협심증환자는제외하였다. 2. 관상동맥조영술연구에포함된모든환자는관상동맥조영을시행하였으며표준 Judkins 방법을사용하여검사하였고, 50% 이상의내경의협착을병변으로하였다. 3. 경동맥및상지동맥의고해상도 B-mode 초음파검사고해상도 B-mode 초음파검사는 8.0 MHz linear array 초음파기기 (Sequoia Ultrasound System, Acuson Co, USA) 를이용하여관상동맥조영술전 24시간내에모든환자에게시행하였다. 한명의연구자가경동맥및상지동맥을관찰하고측정하였으며, 녹화된자료를다른한명의연구자에의해검증하는방법으로관찰자간, 관찰자내측정오류를최소화하고자하였다. 좌우총경동맥은총경동맥이분지되기직전까지관찰하였으며근접벽과원위벽을투사하여장축도와단축도를보면서경화반을관찰하였고, 적당한장축도를얻어서이완기말에서초음파기기에내장된소프트웨어를이용하여각각 IMT (intima media thickness), IAD (interadventitial diameter), LD (luminal diameter) 를구하였다 ( 그림 1). 급성관상동맥질환환자 37명과안정형협심증 21명을대상으로우상지동맥의특징도관찰하였다. 우상지동맥은팔오금 (antecubital fossa) 에서장축도와단축도를보면서경화반을관찰하였고, 적당한장축도를얻어서총경동맥에서와같이 IMT, IAD 및 LD를구하였다. 경동맥 IMT는원위벽의초음파첫째선에서두번째초음파선까지의거리를측정하였고, 첫째선은내강과내피세포와의경계를나타내고두번째초음파선은혈관외피에서콜라겐을포함한상부벽을나타낸다. 근위혈관벽의첫째선과원위혈관벽의첫째선과의거리를 luminal diameter (LD) 라고정의하였고, 근위혈관벽의둘째선과원위혈관벽의둘째선간의거리를 interadventitial diameter (IAD) 라고정의하였다. 최대 IMT (IMTmax) 는동맥경화반이있는경우에는동맥경화반에서 IMT를측정하였고, 동맥경화반이없는경우는총경동맥분지 1 cm 아래에서 IMT를측정하여 IMTmax 라정의하였다. 경동맥의재형성은경동맥 IMTmax 1.0 mm 초과이면서 IAD가 8.0 mm 초과인경우를양성재형성 (positive remodeling) 으로정의하였고, 경동맥 IMTmax가 1.0 mm 초과이고, IAD가 7 mm 미만인경우를음성재형성 (negative remodeling), 양군에포함되지않는경우를무재형성 (no remodeling) 으로정의하였다. 이는다른관찰적연구를종합하여정의한 Kato 등 13) 이사용한정의를참고하여임의로정하였다. 경동맥경화반은다음과같이평가하였다. 경화반은육안적으로주위보다 50% 이상 IMT가두꺼워져있는부위로정의하였다. 경화반은두종류로나누었는데연경화반 (soft plaque) 은초음파에서저음영이거나동질의음영을보이고석회화를시사하는고강도의초음파음영이보이지않는경화반으로, 경경화반 (hard plaque) 은석회화를시사하는고강도의초음파음영이보이는경화반으로정의하였다. 우상지동맥은경동맥과같은방법으로평가하였다. 4. 통계적분석환자의특성은평균 ± 표준편차로표시하였으며초음파로측정한변수들은평균 ± 표준오차로표시하였다. 연속변수는 unpaired t-test로검정하였고, 이산변수는 χ 2 - test로검정하였다. 혈관재형성지표 (IAD/LD) 와관상동맥경화반의수, 급성관상동맥증후군진단여부에따른이변량분석을시행하였고, Pearson 상관계수를구하였다. p 값이 0.05 이하를통계적으로의미가있는것으로간주하였다. 모든통계처리는 SPSS 10.00 (SPSS inc. USA) 통계소프트웨어를사용하였다. 결과급성관상동맥증후군환자군과만성안정형협심증환자군의임상양상즉나이, 성별과위험인자즉 BMI (body mass index), 흡연, 당뇨병과고혈압의유무, 저밀도콜레스테롤치와고밀도콜레스테롤치는양군간에차이가없었다. 병변을가진관상동맥의수와전체관상동맥의경화반수는양군간에차이가없었다. high - 268 -
- 박정랑외 8 인 : 안정형협심증과급성관상동맥증후군에서경동맥재형성 - Table 1. Clinical characteristics and cardiovascular risk factors Mean age, year Men, number (%) BMI (Kg/m 2 ) Active smoking, number (%) Diabetes, number (%) Hypertension, number (%) elevated hscrp >3 mg/dl, number (%) Mean LDL-cholesterol (mg/dl) Mean HDL-cholesterol (mg/dl) No. of diseased vessels (>50%) 1/2/3/main medications, number (%) nitrate calcium channel blocker beta blocker statin Acute coronary syndrome (N=74) 62±11 56 (76) 24.1±2.8 40 (54) 20 (27) 29 (39) 41 (55) * 123.8±41 41.6±9.0 31(42)/30(41)/11(15)/1(1) 11 (15) 18 (24) 8 (11) 6 (8) Chronic stable angina (N=31) 63±9 20 (65) 24.8±3.2 13 (42) 10 (32) 17 (55) 10 (32) 124.5±38 40.6±10 17(55)/7(23)/7(23)/0 11 (35) * 12 (39) 10 (32) * All values are expressed as mean±sd. BMI, body mass index; hscrp, high sensitivity C-reactive protein; N, number of patients * p<0.05 1 (3) p value 0.535 0.243 0.288 0.311 0.177 0.140 0.020 0.936 0.632 0.267 0.019 0.146 0.008 0.619 Figure 1. Measurement of common carotid arteries. IMT, intima media thickness; LD, luminal diameter; IAD, interadventitial diameter. sensitivity C-reactive protein (hscrp) 를측정하여 3 mg/dl 초과인경우를상승한것으로정하여상승군의수를비교하였을때예상대로급성관상동맥증후군에서 41명 (55%), 안정형협심증환자군에서 10명 (32%) 으로통계적으로유의하게급성관상동맥증후군환자군에서많았다 (p=0.020)( 표 1). 양군에서사용중이던약물의조사를하였으나급성관상동맥증후군의경우는약물복용력이없던환자가 대부분이었다. 만성안정형협심증환자군에서항협심증약물로 nitrate와베타차단제계열을많이사용하고있었다. statin 계의약물사용력또한급성관상동맥증후군에서는 6명 (8%), 안정형협심증환자군에서 1명 (3%) 으로사용하고있는환자수가적었으며, 양군간의통계적차이를보이지않았다 (p=0.619)( 표 1). 우총경동맥과좌총경동맥의구조는 IMTmax, LD, IAD와재형성을간접적으로반영하는 IAD/LD 는양군간에차이가없었다 ( 표 2). 비교적동맥경화성변화가오지않는다고알려져있는상지동맥도 IMTmax, LD, IAD와 IAD/LD는양군간에차이가없었으며 ( 표 2), 예상한바와같이모든환자에서동맥경화반은발견되지않았다. 인위적으로정의한무재형성, 양성재형성과음성재형성의빈도는우총경동맥의경우급성관상동맥증후군환자에서 62명 (84%) 과 9명 (12%), 4명 (4%) 이었고안정형협심증환자에서는 25명 (81%), 5명 (16) 과 1명 (3%) 이었다. 좌총경동맥은각각 57명 (77%), 12명 (16%), 5명 (6%) 과 24명 (77%), 6명 (19%), 1명 (3%) 으로양군에서차이가없었다 (p=0.851, p=0.740)( 그림 2). 양측총경동맥에서관찰되는동맥경화반존재여부는 - 269 -
-The Korean Journal of Medicine : Vol. 71, No. 3, 2006 - Table 2. Structure of both common carotid arteries and right carotid artery Acute coronary syndrome (N=74) Chronic stable angina (N=31) p value Right common carotid artery IMTmax, mm LD, mm IAD, mm IAD/LD 0.93±0.06 6.31±0.11 7.92±0.12 1.26±0.016 0.85±0.07 6.35±0.15 7.91±0.16 1.25±0.018 0.485 0.869 0.974 0.716 Left common carotid artery IMTmax, mm LD, mm IAD, mm IAD/LD 1.19±0.09 6.04±0.12 7.84±0.12 1.32±0.027 1.21±0.15 5.90±0.18 7.79±0.15 1.35±0.041 0.869 0.507 0.822 0.596 Right brachial artery (N=37) (N=21) IMTmax, mm LD, mm IAD, mm IAD/LD 0.41±0.016 3.55±0.12 4.33±0.11 1.23±0.08 0.38±0.021 3.31±0.16 4.00±0.16 1.22±0.71 0.515 0.955 0.850 0.469 Values are expressed as mean±sem. IMTmax, maximal intima media thickness; LD, luminal diameter; IAD, Interadventitial diameter; IAD/LD, ratio of interadventitial diameter and luminal diameter. p=0.851 p=0.740 A. Remodeling types of right common carotid artery B. Remodeling types of left common carotid artery Figure 2. Arterial remodeling of both common carotid arteries. 급성관상동맥증후군에서 37 (50%), 안정형협심증환자에서 14명 (45%) 에서보여양군간의미있는차이는없었다 (p=0.528). 다발성경화반은 16명 (22%) 과 3명 (10%) 으로차이가없었고 (p=0.336), 부드러운경화반 (soft plaque) 은 23명 (31%) 과 13명 (42%)(p=0.285), 딱딱한경화반은 16명 (22%) 과 2명 (6%) 으로역시의미있는차이가없었다 (p=0.060)( 그림 3). 재형성지표인 IAD/LD 값은 IMTmax와의미있는상관관계를보여주었고 ( 우총경동맥의 IMTmax 과 IAD/ Figure 3. Frequency and characteristics of plaques in the both common carotid arteries. - 270 -
-Jeong Rang Park, et al : Carotid artery remodeling in acute coronary syndrome and chronic stable angina - IMTmax (cm) IMTmax (cm) A-1. Right common carotid arteries A-2. Left common carotid arteries IMTmax (cm) B-1. Right common carotid arteries IMTmax (cm) B-2. Left common carotid arteries IMTmax (cm) C-1. Right common carotid arteries IMTmax (cm) C-2. Left common carotid arteries Figure 4. Correlation between the common carotid artery remodeling index and IMTmax. (A) In both the acute coronary syndrome and chronic stable angina (B) In patients with the acute coronary syndrome (C) In patients with chronic stable angina. - 271 -
- 대한내과학회지 : 제 71 권제 3 호통권제 553 호 2006 - LD의상관계수 r=0.797 p<0.001, 좌총경동맥의 IMTmax와 IAD/LD 의상관계수 r=0.860, p<0.001), IAD/LD와 IMTmax 와의관계는급성관상동맥증후군과안정형협심증환자각군에서도의미있는양의상관관계를보였다 ( 급성관상동맥증후군 : 우총경동맥 r=0.854, p<0.001, 좌총경동맥 r=0.848, p<0.001, 안정형협심증 : 우총경동맥 r=0.528, p=0.002, 좌총경동맥 r=0.898, p<0.001)( 그림 4). 고찰동맥경화증에서혈관의재형성현상은 Glagov 등 1) 이인간의부검에서얻은혈관조직에서처음증명하였고 McPerson 등 14) 이혈관초음파를이용하여생체에서다시증명하였다. 이후에혈관의내강과동맥경화반을정확하게관찰할수있는혈관초음파가임상에도입되면서관상동맥의재형성에대한많은연구가이루어지고있다. 이들연구의결론은동맥경화반이혈관내강에축적됨에따라전체동맥의크기가증가하는데주로동맥경화반의면적과비례해서저초음파음영을보이는중격이증가하는것에기인한다고한다. 많은환자를연구한결과가동맥경화반의면적과혈관의단면적이양의상관관계를보이고있다 1, 15). 이후에진행된다른연구결과를보면이런혈관의재형성이반드시동맥경화반의내경침범에대한보상적인방향으로진행되지않은경우도있음을보여주고있다. Hausmann 등 16) 이관상동맥에서동맥경화반형성에서적응적으로혈관이확장되지않는음성재형성을최초로보고하였고, 연이어 Wong 등 17) 은같은동맥경화반면적이같더라도어떤동맥은확장되지못하고어떤동맥은실제적으로가장심한협착부위에서혈관면적이감소되는것을볼수있다고하였다. 이런현상은동맥경화증뿐아니라혈관성형술후에생기는재형성 3) 과대퇴동맥 4) 에서도관찰할수있었다. 이처럼동맥의재형성은동맥경화반의특징과동맥경화반의침범정도에따라양성재형성, 음성재형성및무재형성으로각각다른형태로진행될수있음을보여주고있다. 동맥경화반의구조적인특성과동맥재형성의상관관계는처음부검시획득한대퇴동맥과관상동맥의연속단면에서연구되었다 18, 19). 위험경화반 (vulnerable plaque) 은동맥이밖으로자라나는양성재형성에서흔히볼수있었고, 이는위험경화반에있는염증이결국혈관재형 성의가장중요한원인인자임을시사하고있다. 특히안정된동맥경화반에서는주로음성재형성을많이볼수있었던것이이사실을더욱지지하는관찰이다. 이후에여러혈관내초음파검사를이용한연구에서급성관상동맥증후군은원인병변에서양성재형성과더흔히연관되어있고안정형동맥경화반은동맥의음성재형성과연관이되어있다고보고하였다 7, 8, 20). 흥미롭게도 Wexberg 등 21) 은이미존재하는혈관재형성이향후임상양상에어떤영향을미치는지시간적으로관찰하였고그결과, 안정형협심증환자에서관혈적관상동맥시술시양성재형성을보였던환자는음성재형성이관찰되는환자보다주된심혈관계사고의빈도와재혈관개통술의빈도및다른부위에서의협착율이높았다고한다. 이는양성재형성이병변의활성도가높고음성재형성이병변의활성도가안정적임을시사한다. 이런병변의활성도는결국동맥경화반의염증, 파열위험도를나타내므로더많은빈도의급성관상동맥증후군의증상을유발할수있다. 동맥경화반에일어나는염증이양성재형성을일으키는기전으로유추되는것은동맥경화반에서많이생성되는 matrix metalloprotease 22) 와 plasminogen/ plasmin 23) 등이있으며최근에는단핵구의역할도중요하고이런단핵구의 toll-like receptor 4 24) 가관여하는것으로알려져있다. 이와같은급성관상동맥증후군환자에서염증성변화에의한양성재형성의증가는관상동맥에만국한된것이아니고전신의동맥에변화를주기때문에경동맥에도양성재형성의빈도가증가될것이라고유추해볼수있다. 실제로 Kato 등 13) 은급성관상동맥증후군환자에서관상동맥조영을통해복잡병변을하나만가진경우보다여러개를가진경우에총경동맥의 IMT도증가되어있고 IAD도증가되어있어양성재형성이많음을보고하면서급성관상동맥증후군의혈관에서염증성확장재형성은전신적이라고보고하였다. 그러나이논문의비평 25) 에서도언급한바와같이이연구의대상환자가모두급성관상동맥증후군환자들이고이들중에서관상동맥의복잡성동맥경화반의수에따라비교한것이므로실제로경동맥의재형성에영향을미치는지해답을내릴수는없다. 본연구에서는 hscrp 를측정하였고 hscrp 의상한치가 10.2 mg/dl 로평균의비교에제한이있어 AHA/CDC 지침 26) 에따라 3 mg/dl 를초과한경우 hscrp 상승군으로정하여양군을비교하였고, 급 - 272 -
- 박정랑외 8 인 : 안정형협심증과급성관상동맥증후군에서경동맥재형성 - 성관상동맥증후군환자군에서유의하게 hscrp 상승군이많아전신적염증반응의차이를확인할수있었다. 그러나임상양상및관상동맥질환및경화반의수가비슷한급성관상동맥증후군과만성안정형협심증환자에서경동맥과상지동맥을같이관찰한결과양군간의혈관재형성에는큰차이가없다는것을보여주었다. 초기의결과이기는하지만이는혈관의재형성에는전신적인염증인자이외에도국소적인혈역학적인자가더중요하게영향을미치기때문으로추측해볼수있다. 즉, 부순환계의형성에서관찰된바와같이혈류가혈관의재형성에서주요한영향을미치는데이는혈관의내피세포에서혈류의 shear stress를감지하여 metalloprotease 27), monocyte chemoattactant molecule 1 28) 등의발현을증가시키기때문으로생각되어지고있다. 실제로 Boutouyrie 등 29) 은총경동맥과요골동맥의크기는흔히측정하는상지동맥의혈압과평균혈압과는상관관계가없었지만총경동맥의국소혈압과는강한상관관계를보였다고보고하였다. Sho 등 30) 은토끼의동정맥루모형을이용한혈류의변화에따라혈관의크기가변화되는것을관찰하였다. 또한 Pasterkamp 등 31) 은부검혈관을관찰한연구에서동맥의음성재형성은대퇴동맥에많은반면신동맥에는거의없다고보고하고재형성의방향이혈관의위치에따라다르다하였다. 본연구에서도재형성지수에관상동맥의동맥경화반수나환자의임상진단즉, 급성관상동맥증후군인지안정형협심증인지는전혀영향을미치지못하였다. 그러나국소적으로총경동맥의 IMT와동맥경화반의존재가큰영향을미쳤다. 또한관상동맥질환을가진환자였지만상지동맥에서는동맥경화반을발견할수없었으며양군간의 IAD, LD 및 IAD/LD 의차이는관찰할수없었다. 이것으로보아동맥의재형성과정은전신염증인자보다혈관의위치와혈역학적인자가더중요하다고하겠다. 본연구의제한점으로는비록여러가지임상적인요소가잘조절되어있지만 case-control 연구이고, 예수가적다는것이다. 특히혈관의개개인의변이가있기때문에이를극복하기위해서는보다많은증례가필요할것으로생각된다. 본연구에서이런변이를줄이기위해 IAD와 LD, IAD/LD 를나이와 body mass index로교정하여도양군간에차이가없었다 (data not shown). 두번째로총경동맥의재형성기준이임의로정해졌다는점이있겠으나, 아직정확한기준이정해지지않았으며, 환자들의평균과표준편차를이용한기준으로통계처리를시행해보았으나양군에서차이가없어같은결과를보였다. 또한관상동맥혈관내초음파를이용하여급성관상동맥증후군환자와안정형협심증환자에서관상동맥의재형성을측정하여직접적으로총경동맥의재형성을비교하는연구가필요하리라생각된다. 결론적으로본연구에서는급성관상동맥증후군환자에서만성안정형협심증환자에비해총경동맥과상지동맥의재형성의차이는없었다. 따라서혈관의재형성과정은급성관상동맥증후군과같은전신적인염증에의해진행되는전신적인변화보다주로국소적인혈역학적인자가더중요하게관여하는것으로생각되어지며더많은환자에서의연구가진행되어야할것으로생각된다. 요약목적 : 불안정하고염증이활발한동맥경화반에서는보상적인혈관의양성재형성이일어난다. 급성관상동맥증후군환자에서일어나는관상동맥의양성혈관재형성이전신적염증반응에의해경동맥의혈관재형성에도영향을미칠것이라는것을유추해볼수있다. 이에저자는급성관상동맥증후군과만성안정형협심증환자에서경동맥과상지동맥구조의차이를관찰하여급성관상동맥증후군에서발생하는관상동맥의염증으로인한혈관재형성이총경동맥에서도발생하는가를알아보고자본연구를시행하였다. 방법 : 급성관상동맥증후군 74명과안정형협심증 31명을대상으로 B-mode 초음파검사를사용하여양측총경동맥의 IMT, LD, IAD 를측정하였다. 양성재형성은 IMT >1 mm이면서 IAD >8 mm인경우, 음성재형성은 IMT >1 mm이고 IAD <7 mm일때, 그외의경우를무재형성이라정의하여비교하였다. 결과 : 급성관상동맥증후군과안정형협심증양군에서 IMTmax, LD, IAD는차이가없었고, 우총경동맥과좌총경동맥각각의양성재형성, 음성재형성, 무재형성또한차이가없었다. 양총경동맥의동맥경화반의존재유무, 동맥경화반의특징의비교에도두군의차이는없었다. 총경동맥의재형성지표인 IAD/LD는 IMTmax 와의미있는상관관계를보였다 ( 우총경동맥의 IMTmax과 IAD/LD의상관계수 r=0.797 p<0.001, 좌총경동맥의 IMTmax와 IAD/LD의상관계수 r=0.860, p<0.001). - 273 -
-The Korean Journal of Medicine : Vol. 71, No. 3, 2006 - 결론 : 급성관상동맥증후군환자와안정형협심증환자를비교했을때총경동맥의특징에차이가없었다. 따라서혈관의재형성과정은급성관상동맥증후군과같은전신적인염증에의해진행되는전신적인변화보다주로국소적인혈역학적인자가더중요하게관여하는것으로생각되어지며더많은환자에서의연구가진행되어야할것으로생각된다. 중심단어 : 급성관상동맥증후군, 동맥재형성, 경동맥 REFERENCES 1) Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371-1375, 1987 2) Post MJ, de Smet BJ, van der Helm Y, Borst C, Kuntz RE. Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model. Circulation 96:996-1003, 1997 3) Pasterkamp G, Wensing PJ, Post MJ, Hillen B, Mali WP, Borst C. Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries. Circulation 91:1444-1449, 1995 4) Nishioka T, Luo H, Eigler NL, Berglund H, Kim CJ, Siegel RJ. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study. J Am Coll Cardiol 27:1571-1576, 1996 5) Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 12:56-62, 1988 6) Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-tomoderate coronary artery disease? Circulation 78:1157-1166, 1988 7) von Birgelen C, Klinkhart W, Mintz GS, Papatheodorou A, Herrmann J, Baumgart D, Haude M, Wieneke H, Ge J, Erbel R. Plaque distribution and vascular remodeling of ruptured and non-ruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo. J Am Coll Cardiol 37:1864-1870, 2001 8) Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 101:598-603, 2000 9) Crouse JR, Goldbourt U, Evans G, Pinsky J, Sharrett AR, Sorlie P, Riley W, Heiss G. Arterial enlargement in the atherosclerosis risk in communities (ARIC) cohort: in vivo quantification of carotid arterial enlargement. Stroke 25:1354-1359, 1994 10) Steinke W, Els T, Hennerici M. Compensatory carotid artery dilatation in early atherosclerosis. Circulation 89:2578-2581, 1994 11) Kiechl S, Willeit J. The natural course of atherosclerosis: part II. vascular remodeling. Arterioscler Thromb Vasc Biol 19:1491-1498, 1999 12) Terry JG, Tang R, Espeland MA, Davis DH, Vieira JL, Mercuri MF, Crouse JR 3rd. Carotid arterial structure in patients with documented coronary artery disease and disease-free control subjects. Circulation 107:1146-1151, 2003 13) Kato M, Dote K, Habara S, Takemoto H, Goto K, Nakaoka K. Clinical implications of carotid artery remodeling in acute coronary syndrome: ultrasonographic assessment of positive remodeling. J Am Coll Cardiol 42:1026-1032, 2003 14) McPherson DD, Sirna SJ, Hiratzka LF, Thorpe L, Armstrong ML, Marcus ML, Kerber RE. Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis. J Am Coll Cardiol 17:79-86, 1991 15) Ge J, Erbel R, Zamorano J, Koch L, Kearney P, Gorge G, Gerber T, Meyer J. Coronary artery remodeling in atherosclerotic disease: an intravascular ultrasonic study in vivo. Coron Artery Dis 4:981-986, 1993 16) Haussman D, Mullen WL, Friedrich GJ, Fitzgerald PJ, Yock PG. Variability of remodeling in early coronary atherosclerosis: an intravascular ultrasound study [Abstract]. J Am Coll Cardiol 175A, 1994 17) Wong CB, Porter TR, Xie F, Deligonul U. Segmental analysis of coronary arteries with equivalent plaque burden by intravascular ultrasound in patients with and without angiographically significant coronary artery disease. Am J Cardiol 76:598-601, 1995 18) Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE, Hillen B, Borst C. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol 32:655-662, 1998-274 -
-Jeong Rang Park, et al : Carotid artery remodeling in acute coronary syndrome and chronic stable angina - 19) Pasterkamp G, Schoneveld AH, Hijnen DJ, de Kleijn DP, Teepen H, van der Wal AC, Borst C. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery. Atherosclerosis 150: 245-253, 2000 20) Smits PC, Pasterkamp G, Quarles van Ufford MA, Eefting FD, Stella PR, de Jaegere PP, Borst C. Coronary artery disease: arterial remodeling and clinical presentation. Heart 82:461-464, 1999 21) Wexberg P, Gyongyosi M, Sperker W, Kiss K, Yang P, Hassan A, Pasterkamp G, Glogar D. Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris. J Am Coll Cardiol 36:1860-1869, 2000 22) Galis ZS, Johnson C, Godin D, Magid R, Shipley JM, Senior RM, Ivan E. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 91:852-859, 2002 23) Kienast J, Padro T, Steins M, Li CX, Schmid KW, Hammel D, Scheld HH, van de Loo JC. Relation of urokinase-type plasminogen activator expression to presence and severity of atherosclerotic lesions in human coronary arteries. Thromb Haemost 79:579-586, 1998 24) Hollestelle SC, de Vries MR, van Keulen JK, Schoneveld AH, Vink A, Strijder CF, van Middelaar BJ, Pasterkamp G, Quax PH, de Kleijn DP. Toll-like receptor 4 is involved in outward arterial remodeling. Circulation 109:393-398, 2004 25) Tuzcu EM, Schoenhagen P. Acute coronary syndromes, plaque vulnerability, and carotid artery disease: the changing role of atherosclerosis imaging. J Am Coll Cardiol 42:1033-1036, 2003 26) Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Crigui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F. Markers of inflammation and cardiovascular disease: application to clinical and public health practice. Circulation 107:499-511, 2003 27) Magid R, Murphy TJ, Galis ZS. Expression of matrix metalloproteinase-9 in endothelial cells is differentially regulated by shear stress: role of c-myc. J Biol Chem 278:32994-32999, 2003 28) Shyy JY, Lin MC, Han J, Lu Y, Petrime M, Chien S. The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive element is involved in shear stress-induced monocyte chemotactic protein 1 gene expression. Proc Natl Acad Sci U S A 92:8069 8073, 1995 29) Boutouyrie P, Bussy C, Lacolley P, Girerd X, Laloux B, Laurent S. Association between local pulse pressure, mean blood pressure, and large-artery remodeling. Circulation 100:1387-1393, 1999 30) Sho E, Nanjo H, Sho M, Kobayashi M, Komatsu M, Kawamura K, Xu C, Zarins CK, Masuda H. Arterial enlargement, tortuosity, and intimal thickening in response to sequential exposure to high and low wall shear stress. J Vasc Surg 39:601-612, 2004 31) Pasterkamp G, Wensing PJ, Hillen B, Post MJ, Mali WP, Borst C. Impact of local atherosclerotic remodeling on the calculation of percent luminal narrowing. Am J Cardiol 79:402-405, 1997-275 -