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1 Original Article JLA Effect of Adiponectin and Resistin on Coronary Plaque Composition and Coronary Artery Remodeling of Target Lesion in Patients with Stable Angina Jong-Youn Kim 1, Pil-Ki Min 1,2, Young-Won Yoon 1,2, Byoung Kwon Lee 1, Bum-Kee Hong 1, Hyuck Moon Kwon 1 1 Cardiology Division, Heart Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 2 Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea 혈중 Adiponectin 과 Resistin 의농도가안정형협심증환자의표적병변에서관상동맥죽상판의조성과관상동맥재형성에미치는영향 김종윤 1, 민필기 1,2, 윤영원 1,2, 이병권 1, 홍범기 1, 권혁문 1 연세대학교의과대학강남세브란스병원심장내과 1, 연세대학교의과대학혈관대사연구소 2 Objective: The purpose of this study was to investigate the effect of adiponectin and resistin on coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and coronary artery remodeling of target lesion in patients with stable angina. Methods: We prospectively enrolled 48 patients who underwent coronary angiography and VH IVUS for stable angina (27 men, 61±9 years of age). Preintervention grayscale and VH IVUS analysis was done across the target lesion. Planar VH IVUS analysis at the minimum luminal site and volumetric analysis over a 10-mm-long segment centered at the minimum luminal site were performed. The subjects were divided into 2 groups based on remodeling index (RI): positive remodeling (PR) defined as RI>1.0 and non-pr as RI 1.0. Blood samples for analysis of adiponectin and resistin were obtained from the femoral artery before coronary angioplasty. Results: Of the 48 patients enrolled, 23 (48%) had PR in their target lesion and 25 (52%) were non-pr group. Clinical and angiographic characteristics, VH IVUS parameters were not different between the PR and the non-pr groups. Adiponectin and resistin levels showed no significant correlations with coronary plaque composition evaluated with VH IVUS. Adiponectin showed no significant difference between the two groups. However, resistin showed trend toward higher level in non-pr group (4.17±2.18 ng/ml vs. 6.11±4.26 ng/ml, P=0.056) and a significant negative correlation with RI (r=-0.303, P=0.036). Conclusion: We found a negative correlation between the resistin level and RI of a de-novo target lesion in patients with stable angina. Key Words: Adiponectin, Resistin, Atherosclerotic plaque, Intravascular ultrasound, Arterial remodeling Received: Revised: Accepted: July 9, 2012 July 23, 2012 July 27, 2012 Corresponding Author: Pil-Ki Min, Cardiology Division, Heart Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, 211 Eunju-ro, Gangnam-gu, Seoul , Korea Tel: , Fax: , cardioblues@yuhs.ac * This study was supported by a faculty research grant of Yonsei University College of Medicine for 2007 ( ). 69

2 JOURNAL OF LIPID AND ATHEROSCLEROSIS 서론 죽상동맥경화증은관상동맥질환의주된원인으로알려져있으며혈관내초음파검사가임상에널리활용되면서죽상판 (atheromatous plaque) 의조성이나진행양상에대한많은연구들이이루어져왔다. 죽상동맥경화증이진행함에따라나타나는관상동맥재형성 (remodeling) 은 Glagov 등 1 에의해처음으로보고되었는데, 이후혈관내초음파검사를이용한연구에서도확인되었다. 2 보상성재형성 (positive or compensatory remodeling) 은죽상동맥경화증이진행하면서죽상판의양이늘어남에따라혈관의크기가보상적으로늘어나어느정도까지혈관의내경이유지되는상태이며, 3 주로안정형협심증보다는급성관동맥증후군에서흔히관찰된다. 이러한보상성재형성이외에도죽상동맥경화증이진행되면서혈관의크기가국소적으로줄어드는이른바축소성재형성 (negative or constrictive remodeling) 이관상동맥질환이나중재시술이후의재협착병변에서관상동맥협착의또하나의기전으로알려져있으며 4,5 주로안정형협심증에서흔히관찰되는것으로알려져있다. 6 혈관내초음파검사에 virtual hitology (VH) 기법 (Volcano Therapeutics, CA, USA) 이도입되면서단순히죽상판의존재여부나그분포양상뿐만아니라죽상판의조직특성에대해더많은정보를얻을수있게되었는데, 7 이는혈관내초음파신호의무선주파수 (radiofrequency) 의스펙트럼분석을통하여관상동맥의죽상판을조직특성에따라섬유조직 (fibrous), 지질섬유조직 (fibrofatty), 괴사 (necrotic core), 석회화 (dense calcium) 부위의 4가지요소로감별하여각각다른색깔로구분하여나타내준다. 이기법을이용함으로써혈관내초음파검사에서고위험군의불안정죽상판을좀더세분화해서감별하는것이가능하게되었다. 지방세포에서유래한 adipocytokine은염증반응을촉진하고죽상동맥경화증을촉진하며혈관내피세포의기능을저하시켜심혈관계질환의위험을증가시키는것으로알려져있다. 8,9 이중 adiponectin 과 resistin은이러한전신작용의핵심적인매개체로서서로밀접하게연관되며상반된효과를나타내는것으로알려져있다. 10 Adiponectin 농도가낮을수록관상동맥죽상판의지질성분함량이높고, 11 보상성재형성을보이는환자군에서 adiponectin의농도가낮게나타났다 12 는일부보고들이있으나그수는많지않으며, 특히 resistin이죽상판의조성과관상동맥 재형성에미치는영향에관한연구는거의없는실정이다. 따라서, 본연구에서는대표적인 adipocytokine인 adiponectin 과 resistin 의혈중농도가안정형협심증환자의표적병변에서 VH 혈관내초음파로관찰한관상동맥죽상판의조직특성과관상동맥재형성에미치는영향을살펴보고자하였다. 대상및방법 1. 대상환자 2007년 10월부터 2008년 6월까지강남세브란스병원심장내과에안정형협심증으로입원하여관상동맥조영술및혈관내초음파검사를시행한환자중 20세이상의성인으로단일혈관에대해처음으로관상동맥중재시술을시행받는환자만을대상으로하였으며급성관동맥증후군환자와이전에관상동맥중재시술을받은환자및두개이상의혈관에대해중재시술을시행받는환자는제외하였다. 그밖에병변이혈관의개구부에위치하고있거나만성완전폐색병변, 혈관내초음파의시행이어려운병변을가진환자는제외하였으며, 혈역학적으로불안정한환자, 간기능이저하된환자 (AST/ALT 수치가정상의 3배이상 ) 나신장기능이저하된환자 (serum creatinine >2.0 mg/dl) 등은제외하였다. 시술에대한설명을듣고서면동의서를작성한환자에한해연구를진행하였다. 2. 시술및검사방법모든환자에서시술전 aspirin ( mg) 및 clopidogrel ( mg) 부하용량및 heparin 5000 IU를투여하였고시술하는동안 activated clotting time 이 250 sec 이상유지될수있도록필요에따라 heparin 을추가로정주하였다. 관상동맥조영술은대퇴동맥을통하여통상적인방법으로시행하였으며, 중재적시술이필요한하나의표적병변에대하여중재시술을시행하기전에혈관내초음파검사를시행하였다. 혈관내초음파검사는 20MHz 2.9Fr 혈관내초음파카테터 (Eagle Eye, Volcano Therapeutics, CA, USA) 를이용하여 200 μg의 nitroglycerin을관상동맥내로주입후병변의원위부까지카테터를위치시키고 motorized pullback system 을이용하여초당 0.5 mm 의속도로 pull-back 하면서 gray-scale 과 virtual histology 영상을기계에저장시킨후분석하였다. Gray-scale 혈관내초음파영상에서는 external elastic membrane (EEM), 70

3 Jong-Youn Kim, et al: Effect of Adipocytokine on Coronary Artery Remodeling Table 1. Baseline clinical characteristics PR (N=23) Non-PR (N=25) P value Age (years) 62.9± ± Male 14 (61%) 13 (52%) Height (cm) 165.1± ± Weight (kg) 68.4± ± BMI (kg/m 2 ) 25.0± ± Ejection fraction (%) 68.2± ± Clinical history Hypertension 14 (61%) 17 (68%) Diabetes mellitus 7 (30%) 6 (24%) Current smoker 5 (22%) 7 (28%) Blood lipid levels (mg/dl) Total cholesterol 158.4± ± Triglyceride 138.0± ± HDL-cholesterol 43.5± ± LDL-cholesterol 97.7± ± FBG (mg/dl) 101.1± ± Serum insulin (IU/mL) 5.1± ± HOMA index 1.3± ± Medication Aspirin 22 (96%) 24 (96%) Statin 18 (78%) 21 (84%) ACEI/ARB 20 (87%) 18 (72%) Beta-blockers 11 (48%) 14 (56%) PR: positive remodeling, BMI: body mass index, HDL: high-density lipoprotein, LDL: low-density lipoprotein, FBG: fasting blood glucose, HOMA: homeostatic model assessment, ACEI: angiotensin converting enzyme inhibitor, ARB: angiotensin receptor blocker lumen, plaque and media (P&M) 을각각분석하였고 virtual histology 분석을통하여 P&M 조직의특성을각각 fibrotic, fibrofatty, necrotic core, dense calcium으로분류하였다. 표적병변에서혈관내경이가장좁은지점을선택하여 EEM, lumen, P&M의단면적을구하였고, virtual histology상의 4가지조직특성의백분율을구하였다. 관상동맥재형성지수 (remodeling index) 는최소내경을가지는병변의 EEM을 reference EEM으로나눈값으로정의하였으며 plaque burden 은 EEM에서 P&M가차지하는백분율로정의하였다. 관상동맥재형성지수에따라전체환자를재형성지수가 1.0 보다큰보상성재형성군 (positive remodeling; PR) 과 1.0 이하의보상성재형성이없는군 (non-pr) 으로나누어분석하였다. 최소내경을가지는지점을중심으로근위부와원위부각각 5 mm 지점까지총 10 mm의혈관에대해 1 mm 간격으로 pcvh software (Volcano Therapeutics) 를이용하여영상을분석하여체적분석을시행하 였다. EEM, lumen, P&M의체적을각각구하였고 virtual histology 를이용한죽상경화반의 4가지조직특성에따라각각의체적의백분율을구하였다. 시술당일아침에 high sensitivity C-reactive protein (hs-crp) 를포함한기본적인혈액검사를위한채혈을시행하였고 adiponectin 과 resistin의측정을위한채혈은시술직전혈액을채취하여원심분리후영하 80도에보관하였다가이후에외부검사기관 ( 서울의과학연구소 ) 에의뢰하여분석하였다. Adiponectin 은 human adiponectin 125 tubes RIA kit (Linco Research, St. Charles, MO, USA) 를이용하였고, resistin은 Quantikine R human Resistin Immunoassay (R&D systems, Minneapolis, MN, USA) 를이용하여분석하였다. 3. 통계분석자료의통계처리와분석은 PASW statistics version

4 JOURNAL OF LIPID AND ATHEROSCLEROSIS Table 2. Angiographic Characteristics PR (N=23) Non-PR (N=25) P value Number of coronary artery disease vessel disease 10 (44%) 14 (56%) 2 vessel disease 8 (35%) 5 (20%) 3 vessel disease 1 (4%) 4 (16%) Target plaque location LAD/LCX/RCA 19/1/3 22/2/1 Lesion length (mm) 21.6± ± Reference diameter (mm) 3.2± ± Minimum lumen diameter (mm) 0.8± ± Diameter stenosis (%) 75.0± ± PR: positive remodeling, LAD: left anterior descending artery, LCX: left circumflex artery, RCA: right coronary artery, AHA: American Heart Association, ACC: American College of Cardiology Table 3. Data for Intravascular Ultrasound and Virtual Histology PR (N=23) Non-PR (N=25) P value CSA with minimum lumen area EEM CSA (mm 2 ) 15.2± ± Lumen CSA (mm 2 ) 4.9± ± P&M CSA (mm 2 ) 10.3± ± Plaque burden (%) 66.4± ± Fibrous CSA (%) 57.4± ± Fibrofatty CSA (%) 11.8± ± Necrotic core CSA (%) 23.5± ± Dense calcium CSA (%) 7.4± ± Remodeling index 1.2± ±0.1 <0.001 Volumetric analysis EEM volume (mm 3 ) 134.3± ± Lumen volume (mm 3 ) 50.0± ± P&M volume (mm 3 ) 84.3± ± Plaque burden (%) 60.9± ± Fibrous volume (%) 58.5± ± Fibrofatty volume (%) 11.3± ± Necrotic core volume (%) 23.0± ± Dense calcium volume (%) 7.2± ± PR: positive remodeling, CSA: cross sectional area, EEM: external elastic membrane, P&M: plaque and media (SPSS, Inc., Chicago, IL, USA) 를이용하였다. 범주형자료는백분율로표시하고 chi-square 분석으로비교하였고, 연속형자료는평균 ± 표준편차로표시하고 unpaired t-test를이용하여분석하였다. 두연속변수의관련성은 Pearson s correlation coefficient를이용한단순상관분석을시행하였다. P 값이 0.05 미만인경우에통계학적으로유의한것으로간주하였다. 결과 본연구에는총 48 명의환자가등록되었고이중남자가 27 명, 72

5 Jong-Youn Kim, et al: Effect of Adipocytokine on Coronary Artery Remodeling Table 4. Correlations of adiponectin, resistin, and hs-crp with coronary plaque composition determined by virtual histology intravascular ultrasound Biomarkers Plaque composition r P value Adiponectin CSA with minimum lumen area Fibrous CSA (%) Fibrofatty CSA (%) Necrotic core CSA (%) Dense calcium CSA (%) Volumetric analysis Fibrous volume (%) Fibrofatty volume (%) Necrotic core volume (%) Dense calcium volume (%) Resistin CSA with minimum lumen area Fibrous CSA (%) Fibrofatty CSA (%) Necrotic core CSA (%) Dense calcium CSA (%) Volumetric analysis Fibrous volume (%) Fibrofatty volume (%) Necrotic core volume (%) Dense calcium volume (%) hs-crp CSA with minimum lumen area Fibrous CSA (%) Fibrofatty CSA (%) Necrotic core CSA (%) Dense calcium CSA (%) Volumetric analysis Fibrous volume (%) Fibrofatty volume (%) Necrotic core volume (%) Dense calcium volume (%) hs-crp: high sensitivity C-reactive protein, CSA: cross sectional area. 평균연령은 61±9세였다. 관상동맥재형성지수에따라분류하였을때 PR군이 23명, Non-PR 군이 25명이었으며이들의기본적인특성은 Table 1과같았으며두군간에임상적인특성과생화학적검사결과및약물복용의과거력에서의미있는차이는보이지않았다. 관상동맥조영술상단일혈관질환이각각 44%, 56% 로가장많았으며표적병변이위치한혈관은대부분좌전하행지였고, 표적병변의협착정도나병변의길이, 혈관크기에있어서도양군간에의미있는차이는없었다 (Table 2). 혈관내초음파소견을보면협착이가장심한병변에서죽상경화반의면적이 PR군에서크게나타났고 (10.3±4.1 mm 2 vs. 8.0±3.6 mm 2, P =0.046), 체적분석에서는 PR군에서 Lumen 의체적이적고 (50.0±16.9 mm 3 vs. 69.1±24.6 mm 3, P = 0.003) plaque burden 이더높게나타났다 (60.9±12.5% vs. 52.7±9.02%, P =0.013) (Table 3). 하지만 virtual histology 를이용한분석에서는면적과체적분석모두에서양군간에죽상경화반의조성에있어서뚜렷한차이를보이지않았다. 혈중 adiponectin, resistin 및 hs-crp의농도가 virtual histology 로평가한죽상경화반의조성에미치는영향을분석하기위하여상관분석을시행하였으나섬유조직, 지질섬유조직, 괴사, 석회화등의조성은모두이들과유의한상관관계를보이지 73

6 JOURNAL OF LIPID AND ATHEROSCLEROSIS (A) (B) (C) Fig. 1. Level of (A) adiponectin, (B) resistin, and (C) hs-crp in the PR and Non-PR groups. The line within the box denotes the median, and the box spans the interquartile range (25th to 75th percentiles). The whiskers extend from the 10th to 90th percentiles. PR, positive remodeling; hs-crp, high sensitivity C-reactive protein. (A) (B) Fig. 2. Correlation between coronary artery remodeling index and (A) resistin (r=-0.303, P =0.036, y=-0.017x+1.068) or (B) hs-crp (r=0.327, P =0.035, y=0.027x+0.942). hs-crp, high sensitivity C-reactive protein. 않았다 (Table 4). Adiponectin의혈중농도는 PR군과 Non-PR 군사이에유의한차이를보이지않았다 (5.18±2.90 μg/ml vs. 5.79±4.99 μg/ml, P =0.606) (Fig. 1A). Resistin과 hs-crp 또한양군간에통계학적으로의미있는차이는없었으나 resistin은 Non-PR 군에서다소높은경향을보였고 (4.17±2.18 ng/ml vs. 6.11±4.26 ng/ml, P =0.056) (Fig. 1B), hs-crp는 PR군에서높은경향을나타내었다 (2.86±3.00 mg/l vs. 1.42±1.42 mg/l, P =0.053) (Fig. 1C). Resistin과관상동맥재형성지수와의연관성을분석한결과재형성지수는 resistin과뚜렷한음의상관관계를보여혈중 resistin의농도가높을수록재형성지수는낮게나타났다 (r= , P =0.036) (Fig. 2A). 반면에 hs-crp의농도가높을수 록재형성지수는높게나타나뚜렷한양의상관관계를보였다 (r= 0.327, P =0.035) (Fig. 2B). Adiponectin의경우관상동맥재형성지수와는의미있는상관관계를보이지않았으나전체환자에서표적병변의 plaque burden과음의상관관계를보여혈중 adiponectin의농도가높을수록표적병변의 plaque burden이적었다 (r=-0.316, P =0.029) (Fig. 3). 고찰 본연구에서는안정형협심증환자에서 adiponectin과 resistin의혈중농도가표적병변죽상판의조성과관상동맥재형성에미치는영향을살펴보았다. VH 혈관내초음파로관찰한 74

7 Jong-Youn Kim, et al: Effect of Adipocytokine on Coronary Artery Remodeling Fig. 3. Correlation between target lesion plaque burden and adiponectin (r=-0.316, P =0.029, y=-0.001x ). 관상동맥죽상판의조직특성과관련해서는 adiponectin 이나 resistin 모두의미있는연관성을보이지않았으며, 관상동맥재형성의경우 adiponectin 은유의한상관관계를보이지않았으나 resistin의경우재형성지수가낮을수록높은경향을보였다. 아울러 hs-crp는죽상판의조직특성과의연관성은발견하지못했으나관상동맥재형성지수가높을수록높은경향을나타내었다. Adiponectin 은당뇨병이나대사증후군의발생에있어중요한역할을하는것으로알려져있으며비만이나당뇨병, 관상동맥질환을가진환자에서혈중농도가유의하게감소되어있다고널리알려져있다 뿐만아니라안정형협심증환자에비해급성관동맥증후군환자에서특히그농도가감소되어있고, 특히병변의개수가많을수록, 복잡한병변을가진환자일수록그농도가감소되어있다는보고도있다. 18 안정형협심증환자에서 adiponectin과죽상판의특성과의연관성은대부분의연구에서급성관동맥증후군환자에서처럼병변이복잡하거나 18 석회화성분이적고지질성분이많은고위험죽상판을가진환자일수록그농도가낮게나타난다 11,19 고보고하고있으나 Otake 등 20 의연구에서는급성관동맥증후군을가진환자군과는달리안정형협심증환자군에서는 adiponectin과죽상판의조성과의연관성을발견하지못하였다. 본연구도안정형협심증환자를대상으로하였고대상환자수도상대적으로적어 adiponectin 과죽상판의조직특성과의연관성은발견할수없었다. 다만 plaque burden 과는음의상관관계를보여 plaque burden 이더높은환자일수록 adiponectin 의농도가낮게나타나이전연구들과유사한결과를보여주었다. Resistin의경우당뇨병이나관상동맥질환에서몇몇 염증표지인자들과의연관성이보고되긴했으나, 21,22 죽상판의조성과관련한연구는없으며, 본연구에서도 resistin과죽상판의조직특성과의관련성은발견하지못하였다. 관상동맥재형성과 adipocytokine 에대한연구는많지않은데, Iwata 등 12 은안정형협심증환자 100명을대상으로 adiponectin, TNF-α, hs-crp 와관상동맥재형성과의관련성을조사하였다. 이연구에서보상성재형성을보인군과보상성재형성이없었던군을비교한결과 TNF-α와 hs-crp의농도는차이가없었으나 adiponectin은보상성재형성을보였던군에서유의하게낮았다. 또한, 다른여러인자들을고려했을때에도 adiponectin 은보상성재형성을예측하는독립적인예측인자임을보고하였으며, 그기전은명확하지않으나아마도 adiponecin이죽상판의염증반응을감소시켜죽상판의안정화에기여할것으로생각하였다. 한편, 일부연구에서는 adiponectin 이좌심실재형성에관여하여 adiponectin이높을수록좌심실질량이낮았다는보고도있다. 23 하지만, 본연구에서는이러한 adiponectin의효과를관찰할수없었고오히려 hs-crp가높을수록관상동맥재형성지수가큰경향을보여주었다. Resistin의경우관상동맥재형성과관련된연구는없으나 Reilly 등 22 의연구에서 resistin의농도가높을수록컴퓨터단층촬영으로관찰한관상동맥의석회화점수가높게나타남을보고하였다. Grayscale 혈관내초음파를이용한연구들 24,25 에서는일반적으로축소성재형성을보이는죽상판에서석회화성분의함량이높은것으로보고하고있어본연구에서 resistin의농도가높을수록관상동맥재형성지수가낮아지는것을연관지어생각해볼수있겠으나 VH 혈관내초음파를이용한연구들에서는혈관재형성과죽상판석회화정도의연관성에대해다소다른결과를보여주고있다. 관상동맥재형성과 VH 혈관내초음파를이용한죽상판의조직성분들의비교연구들을보면보상성재형성을보이는관상동맥죽상판에서지질함량이높고석회화성분이적게나타난다고보고한연구들도있으나, 일부연구들에서는상반된결과를보여주었다. 29,30 당뇨병이관상동맥의죽상동맥경화증의진행과혈관재형성에대한영향을고찰했던한연구 31 에서는당뇨병환자군에서좀더광범위한죽상동맥경화증의진행을보였고보상성재형성이잘나타나지않았는데아직정확한기전은알려져있지않으나본연구에서 resistin의농도가높을수록보상성재형성보다는축소성재형성이나타나는현상으로미루어당뇨병에서의혈관재형성양상이일부 adipocytokine의영향을받을것으로생각해볼수있겠다. 75

8 JOURNAL OF LIPID AND ATHEROSCLEROSIS 관상동맥재형성은사실죽상동맥경화증이진행하면서나타나는동적인과정이기때문에어느한시점에서의결과를가지고판단하기에는어려운점이있으며기존의연구결과들이다소상이한결과를보여주는것도어느정도단면연구의한계라고볼수있을것이다. 또한 VH 혈관내초음파를이용하여관찰한죽상판의조직특성도이전의 grayscale에비해서는진일보한방법이지만이역시한계가있어실제의조직병리학적특성을완벽히반영할수없다고하겠다. 본연구역시단면연구이며대상환자수가많지않고상대적으로관상동맥질환의진행이심하지않았던안정형협심증환자들을대상으로하고있어죽상판의조직특성이나재형성의미세한차이들을비교하기에는한계가있었을것으로생각한다. 또한서로다른길이의표적병변들을비교하기위하여전체병변을보지않고가장협착이심한병변주변의 10 mm만을분석하였는데, 이러한방법적인차이도이전연구결과들과의차이를초래했을가능성도있다. 죽상동맥경화증의진행은혈관의모든부위에서동일하지않고죽상판의조성이나관상동맥재형성또한진행시점에따라달라질수있기때문에 adipocytokine의영향을좀더잘이해하고고찰하기위해서는향후폭넓은환자를대상으로장기간의비교관찰연구가필요할것으로생각한다. 안정형협심증환자를대상으로한본연구에서 adiponectin 과 resistin 의농도는표적병변의죽상판조성과는의미있는연관관계가없었으며, 관상동맥재형성의경우혈중 resistin의농도가높을수록관상동맥재형성지수가낮게나타났고, adiponectin 의농도는재형성지수와뚜렷한연관관계를보이지않았다. 참고문헌 1. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316: Hermiller JB, Tenaglia AN, Kisslo KB, Phillips HR, Bashore TM, Stack RS, Davidson CJ. In vivo validation of compensatory enlargement of atherosclerotic coronary arteries. Am J Cardiol 1993;71: Losordo DW, Rosenfield K, Kaufman J, Pieczek A, Isner JM. Focal compensatory enlargement of human arteries in response to progressive atherosclerosis. In vivo documentation using intravascular ultrasound. Circulation 1994;89: 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 1995;91: Kimura T, Kaburagi S, Tamura T, Yokoi H, Nakagawa Y, Hamasaki N, Nosaka H, Nobuyoshi M, Mintz GS, Popma JJ, Leon MB. Remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy. Circulation 1997;96: 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 2000;101: Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002;106: Burnett MS, Lee CW, Kinnaird TD, Stabile E, Durrani S, Dullum MK, Devaney JM, Fishman C, Stamou S, Canos D, Zbinden S, Clavijo LC, Jang GJ, Andrews JA, Zhu J, Epstein SE. The potential role of resistin in atherogenesis. Atherosclerosis 2005;182: Frankel DS, Vasan RS, D'Agostino RB, Sr., Benjamin EJ, Levy D, Wang TJ, Meigs JB. Resistin, adiponectin, and risk of heart failure the Framingham offspring study. J Am Coll Cardiol 2009;53: Yaturu S, Daberry RP, Rains J, Jain S. Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes. Cytokine 2006;34: Marso SP, Mehta SK, Frutkin A, House JA, McCrary JR, Kulkarni KR. Low adiponectin levels are associated with atherogenic dyslipidemia and lipid-rich plaque in nondiabetic coronary arteries. Diabetes Care 2008;31: Iwata A, Miura S, Mori K, Kawamura A, Nishikawa H, Saku K. Associations between metabolic factors and coronary plaque growth or arterial remodeling as assessed by intravascular ultrasound in patients with stable angina. Hypertens Res 2008;31: Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, 76

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$(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])$ Cardiovascular Disease in Metabolic Syndrome 김상현 보라매병원내과 서울대학교의과대학내과학교실 Contents Metabolic syndrome and Cardiovascular system CVD Mortality Coronary artery disease Heart failure Atrial fibrillation Management