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1 대한내과학회지 : 제 82 권제 1 호 안정형협심증환자에서 C- 반응성단백질농도의증가 1 전남대학교의과대학예방의학교실, 2 광주보훈병원심혈관센터, 3 여수전남병원내과 최은진 1 신민호 1 강원유 2 황선호 2 김완 2 박승욱 3 Elevated hs-crp in Patients with Stable Angina Pectoris Eun Jin Choi 1,Min-HoShin 1, Won Yu Kang 2, Sun Ho Hwang 2,WanKim 2, and Seung Wook Bak 3 1 Department of Preventive Medicine, Chonnam National University Medical School, Gwangju; 2 Cardiovascular Center, Gwangju Veterans Hospital, Gwangju; 3 Department of Internal Medicine, Yeosu Chonnam Hospital, Yeosu, Korea Background/Aims: The association between inflammatory markers and the severity of coronary artery disease (CAD) in patients with stable angina pectoris remains controversial. This study explored the relationships between the serum high-sensitivity CRP (hs-crp) level and severity of coronary atherosclerosis in patients with stable angina. Methods: The study enrolled 377 stable angina patients (298 males, 79 females) undergoing coronary angiography from June 2006 to August Based on the coronary angiography results, they were divided into two groups according to the diameter of stenosis (DS): Group I (DS 50%) and Group II (DS < 50%). Multivariate logistic regression was used to examine the relationship between the hs-crp level (high hs-crp 3.0 mg/l versus low hs-crp < 3.0 mg/l) and the severity of coronary stenosis. Results: Group I had higher hs-crp levels than Group II [median hs-crp (interquartile range); 0.70 ( ) versus 1.11 ( ) mg/l, p < 0.001]. After adjusting for major cardiovascular risk factors, a high hs-crp level was significantly related to the severity of coronary atherosclerosis (OR 1.95, 95% CI = ). Conclusions: Our data show that patients with 50% coronary stenosis have higher hs-crp levels than patients with < 50% coronary stenosis and stable angina. Further study is needed to define the role of hs-crp in the progression of angina pectoris. (Korean J Med 2012;82:45-51) Keywords: Atherosclerosis; C-reactive protein; Coronary stenosis; Coronary angiography 서론염증반응이동맥경화의발생과연관되어있고동맥경화반의파열및관상동맥혈전증을가속화시켜급성관동맥증후군의병인에중요한역할을할수있음이알려지고있 다 [1,2]. C-반응성단백질 (C-reactive protein, CRP) 은신체에서전반적인염증반응을알아볼수있는단순하고객관적인지표로써 [3], 다른급성반응상물질보다빠르게합성및분해되며, 조직손상과염증이계속되면높은값을유지하므로염증활성도를가장잘나타낸다 [4]. 최근에는동맥경화증을 Received: Revised: Accepted: Correspondence to Min Ho Shin, M.D., Ph.D. Department of Preventive Medicine, Chonnam National University Medical School, 5 Hak 1-dong, Dong-gu, Gwangju , Korea Tel: , Fax: , mhshinx@paran.com

2 - The Korean Journal of Medicine: Vol. 82, No. 1, 유발하는염증의정도를반영할뿐만아니라심혈관계염증반응및혈전의형성및파열에도직접적인역할을하는것으로밝혀졌다 [5]. 기존의여러연구들은혈청 CRP 농도와심혈관질환사이의유의한상관관계를보여주고있다 [6-8]. 특히 1984년부터시작되어 8년동안총 936명의건강한중년남성을대상으로진행되었던 MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) 의연구는 CRP의증가가심혈관질환을예측하는좋은지표라고제시하였다 [7]. 또한 Ridker [9] 의연구는건강한여성들에서고감도 C-반응성단백질 (high sensitivity C-reactive protein, hs-crp) 이콜레스테롤, 지단백질 (lipoprotein), 호모시스테인 (homocysteine) 등보다도심혈관질환발생을보다잘예측한다고하였다. 그리고 Thombpson 등 [10] 과 Haverkate 등 [5] 은혈중 CRP 농도증가는안정형, 불안정형협심증환자모두에서관상동맥질환발생의위험도증가와관련이있다고하였다. 불안정형협심증환자에서관상동맥경화의원인이되는죽상경화의발생과진행, 경화반의미란과파열에염증반응이중요한역할을하지만 [11,12], 안정형협심증환자의경우죽상판의진행에의한관상동맥내경의협착이혈류감소의주원인이되어발생한다고알려져있다 [13]. 하지만 Hangartner 등 [14] 의보고에의하면비록안정형협심증환자라고하더라도동맥경화성반의일부는염증의소견을가지고있으며혈전형성의전단계소견을가질수도있다고하였다. Avanzas 등 [15] 도안정형협심증환자에서유의한협착을보인환자군에서혈중 CRP 농도가유의하게높다고보고하였다. 이와같이안정형협심증환자에서혈중 CRP 농도와관상동맥경화의정도의관계에대해서는아직논란이있다고할수있다. 본연구의목적은안정형협심증환자가운데관상동맥조영술을실시하였던환자들을대상으로혈중 hs-crp 농도와관상동맥경화의심각도와의관계를구명하고자하는것이다. 대상및방법대상본연구의대상자는 2006년 6월부터 2010년 8월까지심혈관센터에내원한안정형협심증환자에서관상동맥조영술 을시행한환자 460명가운데 hs-crp 검사를하지않은 73 명과그외흡연력, 총콜레스테롤, 중성지방검사를시행하지않은 10명을제외한 377명 ( 남자 298명, 여자 79명 ) 을대상으로하였다. 자료수집방법및측정자료는 2010년 5월부터 8월까지수집하였다. 심혈관계질환의위험인자들과관상동맥협착에대한자료는의무기록조사를통해수집하였다. 조사변수로는성별, 나이, 흡연력, 고혈압, 당뇨병, 고지혈증, 체질량지수, 총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤을포함하였다. 모든대상자는속옷과검진복만착용한상태에서신장과체중을측정하였으며신장은 0.1 cm, 체중은 0.1 kg 단위까지측정하였다. 비만도를측정하기위하여체질량지수 (body mass index, BMI) 를이용하였으며신장 (m) 의제곱으로체중 (kg) 을나누어계산하였다. 혈압측정은병동에입실하여 5분이상편안한자세로안정을취하도록한후측정한값을사용하였다. 총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤은 TOSHIBA-200FR (Toshiba, Tokyo, Japan) 을이용하여측정하였고, hs-crp는 Behring nephelometer analyzer II (Dade Behring Inc., Marburg, Germany) 기기를이용하여측정하였다. 관상동맥협착은정량적관상동맥조영술 (quantitative coronary angiography, QCA) 시행후 Centricity AI 1000 (GE Healthcare, Nethelands) 을이용하여 50% 이상의협착이있는경우유의한협착이있는것으로분석하였다. 관상동맥경화의정도는 2개이상의혈관에협착이있는경우가장심한협착이있는혈관을기준으로하였다. 비만은 BMI 25 kg/m 2 이상, 고지혈증은총콜레스테롤 240 mg/dl 이상, 중성지방 150 mg/dl 이상인경우상승군으로정의하였고, 고밀도지단백콜레스테롤은 40 mg/dl 미만인경우하강군으로분류하였다. 혈중 hs-crp의수치는미국심장학회의지침 [16] 에따라 3.0 mg/l 이상인경우를상승군으로분류하였다. 분석방법관상동맥내경협착은 50% 이상인군과이하인군으로분류하였고, 측정변수들의기술통계량은비연속변수이면 빈도 (%) 로제시하였으며, 연속변수 ( 체질량지수, 총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤 ) 이면 평균 ± 표준

3 - Eun Jin Choi, et al. hs-crp and coronary atherosclerosis - 편차 로제시하였다. 혈중 hs-crp 측정치는정규분포를하지않았으므로중앙값 ( 사분위수범위 ) 으로나타냈다. 협착유무에따른대상자들의일반적특성은카이제곱분석과 Student's t-test를통해서비교하였으며, hs-crp의경우는비모수적방법인 Mann-Whitney U 검정을통해서비교하였다. 다변량로지스틱회귀분석을통해서혈중 hs-crp 수치와관상동맥경화의심각도와의관련성을교차비 (odds ratio, OR) 와 95% 신뢰구간 (confidence interval, CI) 을구하여평가하였으며, 보정변수로는단변량분석에서유의수준이 0.05 미만으로유의한차이를보인성별, 나이, 고혈압, 당뇨, 고밀도지단백콜레스테롤을포함하였다. 자료의통계분석은 SPSS version 13.0 for Windows (SPSS, Chicago, IL, USA) 를이용하였고, 모든유의성검정은 p < 0.05에서실시하였다. 스테롤은경계수준의유의성을보였고 (p = 0.05), 흡연여부, 고지혈증여부와체질량지수는두군에서유의한차이가없었으며, 총콜레스테롤, 중성지방또한유의한차이를보이지않았다 (Table 1). 관상동맥협착이 50% 이상인군에서혈 결과대상환자의임상적특성조사대상자는전체 377명으로관상동맥협착이 50% 이상인그룹에서남성이유의하게많았고 (p = 0.005), 65세이상의연령이유의하게많았으며 (p = 0.001), 혈압, 당뇨병환자가유의하게많았다 (p = 0.046, p = 0.011). 고밀도지단백콜레 Stenosis < 50% Stenosis 50% Figure 1. Distribution of high sensitive C-reactive protein (hs-crp) by coronary stenosis status. Boxes extend from the 25th to 75th percentiles and are divided by a solid line representing the median of each group. Whiskers extend from the 5th to 95th percentiles. Each outlier is denoted by a dot. The difference in the median hs-crp level between stenosis < 50% (0.70 mg/l) and stenosis 50% (1.11 mg/l) is statistically significant (p-value < 0.001, Mann-Whitney U-test). Table 1. Baseline characteristics of the study subjects Characteristics Stenosis < 50% (n = 205) Stenosis 50% (n = 172) p-value a Men 151 (73.7) 147 (85.5) Age (yr) 61.7 ± ± 7.4 < Age 65 (yr) 61 (29.8) 79 (45.9) Current smoker 42 (20.5) 48 (27.9) Hypertension 133 (64.9) 128 (74.4) Diabetes mellitus 45 (22.0) 58 (33.7) Dyslipidemia 39 (19.0) 41 (23.8) BMI (kg/m 2 ) 24.6 ± ± Total cholesterol (mg/dl) ± ± Triglyceride (mg/dl) ± ± HDL cholesterol (mg/dl) 44.8 ± ± hs-crp (mg/l) b 0.70 ( ) 1.11 ( ) < Values are given as the mean ± standard deviation or n (%). BMI, body mass index; HDL, high-density lipoprotein; hs-crp, high sensitivity C-reactive protein. a p-value, as determined by the t-test or chi-square test as appropriate. b The hs-crp levels are presented as the median with the 25th and 75th percentiles; the p-value was determined using the Mann-Whitney U-test

4 - 대한내과학회지 : 제 82 권제 1 호통권제 617 호 Table 2. The relationship between cardiovascular risk factors and the severity of coronary atherosclerosis as determined by a multiple logistic regression model Characteristics Crude OR (95% CI) Adjusted OR (95% CI) Age 65 (yr) 2.01 ( ) 2.21 ( ) Men 2.10 ( ) 2.18 ( ) hs-crp ( 3.0 mg/l) 2.28 ( ) 1.95 ( ) Diabetes mellitus 1.81 ( ) 1.65 ( ) Hypertension 1.58 ( ) 1.44 ( ) HDL cholesterol (< 40 mg/dl) 1.56 ( ) 1.21 ( ) hs-crp, high sensitivity C-reactive protein; HDL, high-density lipoprotein. 중 hs-crp 의중앙값은 1.11 mg/l로서협착이 50% 이하인군의 0.70 mg/l보다유의하게높았다 (Table 1, Fig. 1). 관상동맥경화의심각도와여러위험요인들에대한로지스틱분석단변량로지스틱회귀분석결과남성에서여성에비해관상동맥협착의위험도가높았으며 65세이상의나이, 고혈압, 당뇨병, 낮은고밀도지단백콜레스테롤, 높은 hs-crp의위험도가높게나타났다. 다변량분석결과에서남성, 65세이상의나이, 높은 hs-crp, 당뇨병은관상동맥협착의위험도가단변량분석과같이유의하게높게나타났으나고혈압, 낮은고밀도지단백콜레스테롤의위험도는유의하지않았다. 혈중 hs-crp가 3.0 mg/l 이상으로높은군에서낮은군에비해관상동맥협착에대한교차비가 2.28 (95% CI = ) 로높았으며, 성별, 나이, 고혈압, 당뇨병, 고밀도지단백콜레스테롤을보정한이후에교차비가 1.95 (95% CI = ) 으로서유의한관련성을보였다 (Table 2). 고찰본연구는혈중 hs-crp 농도와관상동맥경화의심각도와의관계를알아보기위하여심혈관센터에내원한안정형협심증환자에서관상동맥조영술을시행한환자를대상으로실시하였으며, 연구결과심혈관계질환의위험요인들을보정한후혈중 hs-crp가 3.0 mg/l 이상으로높은환자에서낮은환자에비하여관상동맥협착위험이더심하였다. Avanzas 등 [15] 의연구에서 121명의유의한관상동맥협 착을보인안정형협심증환자와 29명의정상관상동맥소견을보인환자의혈중 CRP 농도를비교한결과협착을보였던안정형협심증환자의혈중 CRP 농도가 2.15 mg/dl로정상소견을보였던환자의 0.39 mg/dl에비해유의하게높았다고보고하였다. Zebrack 등 [17] 은급성심근경색증환자를제외한 2,554명의환자를대상으로한연구에서 1,848명의관상동맥질환을가진환자중안정형협심증환자에서혈중 CRP의농도와관상동맥질환의중증도 / 범위가연관성이있음을보고하여본연구결과와일치하는소견을보였다. 즉, 본연구에서는혈중 hs-crp의상승과관상동맥경화의심각도사이에의미있는연관성이있었고, 이것이안정형협심증환자에서상승한혈중 hs-crp 농도가관상동맥협착의중증도를예측할수있는좋은지표가될수있음을나타냈다고할수있다. 그러나 Kim [18] 의연구에서 CRP와염증반응을반영하는또다른지표인적혈구침강속도 (erythrocyte sedimentation rate, ESR) 의증가는불안정형협심증이나급성심근경색증과같은급성관상동맥증후군에서관찰되었고, 안정형협심증에서는정상대조군과차이를보이지않았다. 이러한결과는 Liuzzo 등 [19] 이나 Anderson 등 [20] 의연구결과에서도관찰되는데이를통해그들은염증반응이만성동맥경화의개시에관련된다는것보다는동맥경화반의파열과연관된급성관상동맥증후군의병인에관여할것이라고제안하였다. 죽상경화는관상동맥질환의중요한원인이며, 죽상경화의진행과죽상반의파열기전으로염증이중요한역할을한다는수년간의연구보고가있었다 [19,21]. 동맥경화의진행과관련된염증표지자에대한연구는주로 hscrp, 융해성세포부착분자 (soluble adhesion molecules, sicam-1; soluble

5 - 최은진외 5 인. 안정형협심증환자에서 C- 반응성단백질농도의증가 - InterCellular Adhesion Molecule-1, svcam-1, P & E-selectin 등 ) 와케모카인 (MCP-1, scd40l, IL-6 [Interleukin-6], IL-8 [Interleukin-8]) 등으로이들이각각독립적인위험인자로보고된바있다 [22]. 염증반응을나타내는지표들가운데심혈관질환과가장상관관계가높은지표는 CRP로알려져있는데 [23], CRP 수치와동맥경화등의관계는다음과같이설명될수있다. 염증반응은죽상경화판을불안정하게만들고, 혈전의생성을촉진함으로써관상동맥질환을일으키는데 [12,24], CRP는이러한염증반응을반영해주는단순한지표일수도있다. 하지만 CRP가죽상경화의진행에직접적인영향을끼친다는연구결과들을살펴보면, Pasceri 등 [25] 은 CRP가 E-selectin뿐아니라세포간부착인자 (intercellular adhesive molecule, ICAM-1) 와혈관세포부착인자 (vascular cell adhesive molecule, VCAM-1) 의발현을증가시키는등내피세포에직접적인영향을미친다고하였고, 이외에도 CRP가단핵구의조직인자발현을증가시키고보체를활성화시킴으로써염증반응을진행시키며혈전을유발한다는보고도있었다 [26]. 즉, CRP 자체가혈관벽에서죽상경화증의진행에중요한인자로서역할을한다는것이다. 하지만, 염증반응이나 CRP 가관상동맥질환에있어서직접적인영향을미치지못하며, CRP의상승은단지비특이적인현상이라는주장들도제기되고있다 [27]. 동맥경화증의발생에있어당뇨병은중요한병인으로작용하며, 당뇨병환자의경우관상동맥이외에대뇌동맥등다른중요한혈관분지에도동맥경화증이있는확률이높다 [28]. 또한당뇨병환자의경우그렇지않은경우에비해관상동맥조영술에서다혈관질환이나복잡병변, 관상동맥완전폐쇄등의가능성이높다고하였다 [29]. 본연구에서도당뇨병이있는환자의경우그렇지않은환자에비하여관상동맥협착의위험도가높았다. 본연구에는몇가지제한점을가지고있다. 첫째, 본연구는단면연구로서혈중 hs-crp 농도와관상동맥협착사이에유의한관련성은보여주고있으나관련성을인과관계로해석할때는주의를필요로한다. 둘째, 본연구에서관상동맥의협착정도를알아보기위해사용한관상동맥조영술은관상동맥협착부위의직경협착 (%) 만을나타냄으로관상동맥벽과동맥경화반을보다입체적으로관찰하지못하였다. 그러므로향후관상동맥경화의심각도를평가하기위한혈관내초음파나혈관경과같은기구를사용하여보다세밀 한연구가필요할것으로생각된다. 셋째, 본연구에서는염증지표로혈중 hs-crp 농도만을대상으로하였는데혈중 hs-crp 농도는전신성염증반응을나타내는비특이적인염증지표로서관상동맥내에서생성되는여러가지염증지표들을함께측정하여분석한다면보다정확한결과를얻을수있을것으로생각된다. 넷째, 본연구에서는입원전및입원중혈중 hs-crp의농도에영향을미칠수있는바이러스성질환, 만성폐질환, 관절염등의다양한만성적인염증상태는고려하지못하였다. 마지막으로본연구에서는혈중 hs-crp 농도에영향을줄수있는아스피린이나스타틴계열의약물복용여부에대한조사가포함되지않아서검사한혈중 hs-crp의농도가대표성이떨어진다는점을들수있겠다. 안정형협심증환자에서높은혈중 hs-crp 농도는 50% 이상의관상동맥협착과유의한관련성을보였다. 그러나이러한관련성을설명하기위해서는좀더자세히평가된관상동맥경화의심각도와혈중 hs-crp 농도의상관관계에대한전향적인연구가더이루어져야할것이다. 요약목적 : 본연구는안정형협심증환자중관상동맥조영술을실시하였던환자들을대상으로고감도 C-반응성단백질 (high sensitivity C-reactive protein, hs-crp) 농도와관상동맥질환의정도와의관계를구명하고자하였다. 방법 : 2006년 6월부터 2010년 8월까지광주소재종합병원심혈관센터에내원한안정형협심증환자에서관상동맥조영술을시행한환자 377명 ( 남자 298명, 여자 79명 ) 을대상으로하였다. 자료는 2010년 5월부터 8월까지수집하였다. 심혈관계질환의위험인자들은의무기록조사를통해수집하였고, 관상동맥경화의정도는관상동맥협착이 50% 이상인군과이하인군으로나누어분석하였다. 결과 : 관상동맥협착이 50% 이상인군은전체대상자 377명중 172명으로 45.6% 였다. 혈중 hs-crp가 3.0 mg/l 이상으로높은군에서낮은군에비해관상동맥협착에대한교차비가 2.28 (95% CI = ) 로높았으며성별, 나이, 고혈압, 당뇨병, 고밀도지단백콜레스테롤을보정한이후에교차비가 1.95 (95% CI = ) 으로여전히유의한관련성을보였다

6 - The Korean Journal of Medicine: Vol. 82, No. 1, 결론 : 안정형협심증환자에서높은혈중 hs-crp 농도는 50% 이상의관상동맥협착과유의한관련성을보였다. 그러나이러한관련성을설명하기위해서는좀더자세히평가된관상동맥경화의심각도와혈중 hs-crp 농도의상관관계에대한전향적인연구가더이루어져야할것이다. 중심단어 : 동맥경화 ; C-반응성단백질 ; 관동맥협착 ; 관상동맥조영술 REFERENCES 1. Alexander RW. Inflammation and coronary artery disease. N Engl J Med 1994;331: Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice.circulation 1999;100: Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362: Jaye DL, Waites KB. Clinical applications of C-reactive protein in pediatrics. Pediatr Infect Dis J 1997;16: Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary eventsin stable and unstable angina: European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997;349: Tracy RP, Lemaitre RN, Psaty BM, et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol 1997;17: Koenig W, Sund M, Fröhlich M, et al. C-Reactiveprotein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to Circulation 1999;99: Rohde LE, Hennekens CH, Ridker PM. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol 1999;84: Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103: Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris: European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995;332: Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340: Rader DJ. Inflammatory markers of coronary risk. N Engl J Med 2000;343: Hur SH. Lesion characteristics in patients with acute coronary syndrome: a comparison with lesion in patients with stable angina by intravascular ultrasound. Korean Circ J 2004;34: Hangartner JR, Charleston AJ, Davies MJ, Thomas AC. Morphological characteristics of clinically significant coronary artery stenosis in stable angina. Br Heart J 1986;56: Avanzas P, Arroyo-Espliguero R, Cosín-Sales J, Quiles J, Zouridakis E, Kaski JC. Multiple complex stenoses, high neutrophil count and C-reactive protein levels in patients with chronic stable angina. Atherosclerosis 2004;175: Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107: Zebrack JS, Muhlestein JB, Horne BD, Anderson JL; Intermountain Heart Collaboration Study Group. C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina. J Am Coll Cardiol 2002;39: Kim KH. The role of chronic infection and inflammation in Korean patients with Coronary Artery Disease. Korean Circ J 2000;30: Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994;331: Anderson JL, Carlquist JF, Muhlestein JB, Horne BD, Elmer SP. Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. J Am Coll Cardiol 1998;32: Uccella R, Donnini P, Franzetti I, Gaiazzi M. Serum lipid pattern as severity indicator of angiographically assessed coronary artery disease. Artery 1993;20: Bae JH, Park JS, Hong GR, Shin DG, Kim YJ, Shim BS. Correlation between inflammatory markers and the progression of atherosclerosis in patients with coronary artery disease. Korean J Med 2008;74: Koo BK, Choi DH, Kyung HD, et al. Role of inflammation in stable angina patients without hypercholesterolemia. Korean Circ J 2001;31: Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105: Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells

7 - Eun Jin Choi, et al. hs-crp and coronary atherosclerosis - Circulation 2000;102: Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993;82: Mendall MA, Strachan DP, Butland BK, et al. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J 2000; 21: Zaroff JG, ditommaso DG, Barron HV. A risk model derived from the National Registry of Myocardial Infarction 2 database for predicting mortality after coronary artery bypass grafting during acute myocardial infarction. Am J Cardiol 2002;90: Ko JS, Joo SY, Jeong MH, et al. Predictive factors for heart failure in patients with unstable angina and acute non-st elevation myocardial infarction. Korean Circ J 2004;34:

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