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1 대한진단검사의학회지제 28 권제 5 호 2008 Korean J Lab Med 2008;28: DOI /kjlm 원저 임상화학 Cardiac Troponin I 경도증가의임상적의의 정채림 조성은 홍기숙 이화여자대학교의학전문대학원진단검사의학교실 Clinical Significance of Minor Elevation of Cardiac Troponin I Chae Lim Jung, M.D., Sung Eun Cho, M.D., and Ki Sook Hong, M.D. Department of Laboratory Medicine, School of Medicine, Ewha Womans University, Seoul, Korea Background : Cardiac troponin I (ctni) is known as a sensitive and specific marker for myocardial ischemia. The purposes of this study are to establish cut-off values of ctni for acute myocardial infarction (AMI) and to analyze clinical significance of minor elevation of ctni. Methods : Two hundred and four patients from whom ctni was measured at Ewha Womans University Dongdaemun hospital from January to March, 2006 were enrolled in the study. ctni was measured using Dimension RxL (Dade Behring, USA). The lower limit of detection (LLD), 10% CV value, 99th percentile of healthy individuals, and cut-off value for AMI by ROC curve analysis were determined. Results : LLD, 10% CV value, and 99th percentile of ctni were 0.00 ng/ml, 0.10 ng/ml, and 0.07 ng/ml, respectively. The cut-off value of peak ctni for AMI by ROC curve analysis was 0.13 ng/ml with the sensitivity, specificity, and AUC of 90.9%, 87.7%, and 0.921, respectively. The peak value of ctni of patients with ischemic heart disease (IHD) was higher than that of the patients without IHD (P<0.05). According to the above reference and cut-off values of the initial ctni, patients were categorized into four groups; 0.05 ng/ml (group 1), ng/ml (group 2), ng/ml (group 3), 0.60 ng/ml (group 4), and compared frequencies of AMI, IHD, cardio vascular disease (CVD) and death after 1 month among groups. Frequencies of AMI, IHD, CVD, and death after 1 month were significantly increased as the ctni concentrations were increased (P<0.05). Conclusions : Minor elevation of ctni value, even in group 3 was significantly associated with high incidence of AMI, IHD, CVD, and death rate after 1 month. (Korean J Lab Med 2008;28:339-45) Key Words : 99th percentile of ctni, 10% CV of ctni, AMI cut-off value 서 론 Cardiac troponin I (ctni) 또는 cardiac troponin T (ctnt) 접 수 : 2007년 12월 13일 접수번호 : KJLM2093 수정본접수 : 2008년 9월 1일 게재승인일 : 2008년 9월 1일 교신저자 : 홍기숙 우 서울시양천구목동 이대목동병원진단검사의학과 전화 : , Fax: kshong@ewha.ac.kr 는심근괴사에민감하고심근조직에매우특이적이어서현재심근허혈의진단에가장선호되는표지자이다 [1-3]. 높은민감도와특이도때문에, troponin이정상치보다는높지만심근경색의경계치이하인경우임상적의의를파악하려는연구가이루어지고있다 [4]. 최근지침들에서 troponin의역할이심근경색뿐만아니라불안정협심증및비st분절상승심근경색등의진단및치료를위한위험도층화 (risk stratification) 에까지확대되었다 [5-8]. 현재경도로상승한 troponin의해석에대한통일된지침은마련되어있지않은상황이며최근전세계적으로 339

2 340 정채림 조성은 홍기숙 이에대한관심이커지고그의의에대한연구결과들이계속보고되고있다 [4, 6, 8]. 유럽심장학회와미국심장학회공동위원회 (European Society of Cardiology and American College of Cardiology, ESC/ACC) 는 2000년도에개정된심근경색기준을발표하였다. 생화학표지자인 troponin이나 CK-MB의유의한변화가있으면서허혈증상, 심전도상병적인 Q파의발생, 허혈을나타내는심전도변화, 관상동맥중재시술의 4가지조건중하나이상이있는경우심근경색으로정의하고있다 [1]. 이는 WHO 기준 [9] 보다 troponin의역할이강화된것으로 troponin을심근손상의표준진단지표로지정하고있다. ESC/ACC는심질환이없는정상군의 99백분위수를심근경색의경계치로제안하고있으며이때변이계수 (coefficient of variation, CV) 값이 10% 미만이될것을권고하고있다 [1]. 각검사실마다 troponin 측정에사용하는기기와시약등이다르고정상참고치, 99백분위수, 10% CV 값, ROC 곡선분석에의한경계치, 제조사가제시한경계치등의여러참고치들을다양하게진단기준으로쓰는등표준화가되어있지않다 [2-4]. 따라서한검사실의결과를다른검사실의결과와직접비교할수없으며, 특히 troponin이약간증가한경우적용되는경계치에따라결과해석이달라져진단및치료에어려움을겪을수있다 [2, 3, 10, 11]. 협심증이나심근경색은진단을바로하지못하여적절한치료시기를놓치면환자에게치명적일수있으므로신속하고정확한검사결과가필요하다. 올바른결과해석및진단을위하여각검사기관마다기준치를설정할필요가있다. 본연구에서는본원 ctni의 99 백분위수, 10% CV 값, ROC 곡선분석에의한심근경색의경계치등을설정하여이러한경계치들의임상적의의를검토하고자하였다. 대상및방법 1. 최저검출한계, 10% CV, 99백분위수 ctni의최저검출한계는증류수 20 검체를반복측정하여평균 +3표준편차로정하였다. 10% CV 값은 CLSI EP15-A 지침 [12] 에따라각각 5개의농도별로하루 2번씩 5일동안측정하여총 CV 를구한후그래프를그려서구하였다. 99백분위수는혈액검사, 심전도검사, 심장초음파검사상심혈관질환이없는남자 89명, 여자 129명, 총 218명의 99백분위로정하였다. 본연구에사용한측정시약은 ctni Flex, 기기는 Dimension RxL (Dade Behring, Newark, USA) 이고제조사에서제공한정상 참고치는 0.05 ng/ml 이하, 급성심근경색의경계치는 0.60 ng/ml 이상이었다. 2. 연구대상및검체대상환자 204명은 2006년 1월에서 3월까지이화여자대학교의과대학부속동대문병원에외래또는응급실을내원하여 ctni 측정을의뢰한환자들로 ctni, creatine kinase (CK), CK-MB, lactate dehydrogenase (LD), B-type natriuretic peptide (BNP), C-reactive protein (CRP), glucose, blood urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoproteincholesterol (HDL-C), total cholesterol을동시에측정하였다. ctni는본원에서는증상발현시, 2, 4, 6, 12, 24시간의간격으로측정하는것을원칙으로하고있으며, 증상발현후처음측정한값과경과기간중의최고치를모두기록하였다. 대상환자들의분포는남자 108명, 여자 96 명이었고, 평균연령은 65세였다. 환자들의질환은심혈관질환, 뇌혈관질환, 폐질환, 종양, 위장관질환, 골관절질환, 패혈증, 정신질환, 간담도질환, 신요로계질환, 외상, 내분비질환, 기타쇼크등으로다양한질환들이포함되었다. 본연구에서심근경색은 ESC/ACC 지침에따라 ctni가증상발현후첫 24 시간내에최소 1번이상경계치 ( 정상인군의 99백분위수 ) 를넘으면서전형적인상승-하강양식을보이고동시에다른 4가지조건중 1가지이상을충족시킨경우로정의하여총 33 명으로분류하였다. 다른 4가지조건중 1가지이상을충족하며 1개월후생존여부의추적관찰이가능한경우는 154명이었고, 생존자는 134명, 사망자는 20명이었다. 3. 임상질환에따른 ctni 농도분석 ROC 곡선분석에의한경계치는본원환자 204명의 ctni 최고치와임상기록을참고하여산출하였다. ctni와허혈성심질환과의관계를규명해보기위해허혈성심질환이있는군과없는군으로나누어각각의변수들을비교하였다. 또한앞에서측정한 ctni 농도에따라 204명을네군으로분류한후각군에서의심근경색, 허혈성심질환, 심혈관질환의빈도및 1개월후생존여부, 심질환관련생화학검사결과등을비교하였다. 허혈성심질환은심근허혈로생기는심장장애로서협심증과심근경색을포함하는관상동맥질환을말한다. 심혈관질환에는급성심근경색을포함한허혈성심질환, 울혈성심부전, 심판막질환, 부정맥또는이들질환이중복된경우를모두포함하였다.

3 Minor Elevation of Cardiac Troponin I 통계분석 98.0%, 효율성은 88.0% 이었다 (Fig. 2, Table 1). 통계분석은 SPSS version 12를사용하였다. 연속변수에대해서는 student t 검정또는 Kruskal-Wallis 검정을실시하였고, 비연속변수에대해서는카이제곱검정법과선형대선형결합법을사용하였다. 모든검사결과는평균 ± 표준편차로표시하였고, 모든통계는 ctni의일련의측정치중최초측정치와최고치를기준으로각각분석하였으며 P 값이 0.05 이하일때통계학적으로유의한것으로정하였다. 결 1. ctni의최저검출한계, 10% CV, 99백분위수, ROC 곡선분석 ctni의최저검출한계는 0.00 ng/ml으로평균과표준편차모두 0.00 ng/ml였다. 10% CV 값은 0.10 ng/ml (Fig. 1) 이었으며, 99백분위수는 0.07 ng/ml로범위는 ng/ ml이었다. ROC 곡선에의한심근경색의경계치는 ctni 0.13 ng/ml를기준으로했을때곡선아래면적 (area under the curve, AUC) 은 0.921, 민감도와특이도는 90.9%, 87.7% 로경계치에합당하였고양성예측도와음성예측도는각각 58.8%, Precision (% CV) ctnl (ng/ml) Fig. 1. Total precision profile for cardiac troponin I (ctni). The 10% CV value was 0.10 ng/ml. Table 1. The number of AMI by ctni cut-off of 0.13 ng/ml ctni AMI (N=33) No AMI (N=171) 0.13 ng/ml <0.13 ng/ml Sensitivity, 90.9% (30/33); Specificity, 87.7% (150/171); Positive predictive value, 58.8% (30/51); Negative predictive value, 98.0% (150/153); Efficiency, 88.0% Abbreviations: AMI, acute myocardial infarction; ctni, cardiac troponin I. 과 % CV=0.10 ng/ml 허혈성심질환과비허혈성심질환에서의검사결과비교 허혈성심질환이있는군과없는군에서 ctni를포함한심질환관련생화학검사들을비교하였다. 허혈성심질환군에서 ctni 최고치와 BUN 농도가통계적으로유의하게높았고 HDL-C은낮았다. 통계적으로유의한차이는없었으나연령, ctni 최초치, BNP는허혈성심질환군에서높은경향을보였다 (P>0.05) (Table 2). 3. ctni 농도에따른심질환및사망빈도분석 ctni 최초측정치를 0.05 ng/ml (1군 )(142명), ng/ml (2군)(22명), ng/ml (3군)(30명), 0.60 ng/ ml (4군)(10명) 등네군으로분류하여급성심근경색, 허혈성심질환, 심혈관질환, 사망의빈도를비교하였다 ng/ml 는제조사에서제시한정상참고치 (97.5백분위수), 0.10 ng/ml 는 10% CV 값, 0.60 ng/ml는제조사에서제시한급성심근경색의경계치이다. 본연구에서는 3군이주된관찰대상이었다. 1군과 2군의심근경색빈도는각각 4.2%, 18.2% 였으며 3군과 Table 2. Comparison of laboratory parameters between no IHD population and IHD population No IHD (N=140) Mean±SD IHD (N=64) Mean±SD P value* Age (yr) 64.0± ± ctni (ng/ml) Initial value 0.06± ± Peak value 0.09± ± CK (U/L) 491.3± ± CK-MB (ng/ml) 19.3± ± LD (U/L) 533.5± ± BNP (pg/ml) 237.5± ± Glucose (mg/dl) 140.0± ± BUN (mg/dl) 19.0± ± Cr (mg/dl) 1.34± ± CRP (mg/dl) 5.6± ± TG (mg/dl) 112.8± ± LDL-C (mg/dl) 114.2± ± HDL-C (mg/dl) 48.1± ± Total cholesterol (mg/dl) 178.5± ± *Student t test; P<0.05, statistically significant. Abbreviations: IHD, ischemic heart disease; ctni, cardiac troponin I; CK, creatine kinase; LD, lactate dehydrogenase; BNP, B-type natriuretic peptide; CRP, C-reactive protein; BUN, blood urea nitrogen; Cr, creatinine; TG, triglyceride; LDL-C, low density lipoprotein-cholesterol; HDL- C, high density lipoprotein-cholesterol.

4 342 정채림 조성은 홍기숙 Sensitivity ng/ml AUC= Specificity Fig. 2. ROC curve for ctni in 204 patients with or without AMI. Abbreviations: AUC, area under the curve; ctni, cardiac troponin I; AMI, acute myocardial infarction. 4군의심근경색빈도는각각 53.3%, 70.0% 로 ctni가높은군일수록심근경색빈도가증가하는것을볼수있었다. 허혈성심질환은 1군과 2군에서는 19.0%, 31.8% 이던것이 3군에서는 70.0%, 4군에서 90.0% 로 ctni가증가할수록빈도가증가하였고, 심혈관질환의빈도도 1군, 2군에서는 29.6%, 50.0% 였던것에비해 3군에서 86.7%, 4군에서 90.0% 로 ctni가높은군일수록증가하였다. 1개월사망률은 1군과 2군에서 6.3%, 21.4%, 3군과 4군에서각각 36.8%, 30.0% 로 ctni가높은군이사망도증가하였으나큰차이는없었다 (Table 3). 4. ctni 농도에따른생화학검사결과 ctni 군들에따라심질환관련생화학검사결과들을비교한결과통계적으로유의했던검사들은 CK, CK-MB, LD, BNP, BUN, Cr 이었다. ctni가높은군일수록대체적으로다른검사결과들도높았으며, CK, CK-MB, LD는 3군에서, BNP는 4군에서가장높았다 (Table 4). Table 3. Incidence of AMI, IHD, CVD, and death according to initial ctni values ctni (ng/ml) Group (N=142) [%, (N)] Group (N=22) [%, (N)] Group (N=30) [%, (N)] Group (N=10) [%, (N)] P value* No AMI (N=171) 95.8 (136) 81.8 (18) 46.7 (14) 30.0 (3) AMI (N=33) 4.2 (6) 18.2 (4) 53.3 (16) 70.0 (7) No IHD (N=140) 81.0 (115) 68.2 (15) 30.0 (9) 10.0 (1) IHD (N=64) 19.0 (27) 31.8 (7) 70.0 (21) 90.0 (9) No CVD (N=116) 70.4 (100) 50.0 (11) 13.3 (4) 10.0 (1) CVD (N=88) 29.6 (42) 50.0 (11) 86.7 (26) 90.0 (9) Survival (N=134) 93.7 (104) 78.6 (11) 63.2 (12) 70.0 (7) Death (N=20) 6.3 (7) 21.4 (3) 36.8 (7) 30.0 (3) *Statistically significant by chi-square analysis (P<0.05). Abbreviations: AMI, acute myocardial infarction; IHD, ischemic heart disease; CVD, cardiovascular diseases. Table 4. Results of laboratory parameters according to initial ctni values ctni (ng/ml) Group (N=142) [%, (N)] Group (N=22) [%, (N)] Group (N=30) [%, (N)] Group (N=10) [%, (N)] P value* CK (U/L) 169.6± ± ,974.2± ± CK-MB (ng/ml) 1.7± ± ± ± LD (U/L) 504.8± ± ± ± BNP (pg/ml) 176.2± ± ±1, ,048.5±1, BUN (pg/ml) 19.0± ± ± ± Cr (mg/dl) 1.00± ± ± ± *Statistically significant by Kruskall-Wallis test (P<0.05). Abbreviations: ctni, cardiac troponin I; CK, creatine kinase; LD, lactate dehydrogenase; BNP, B-type natriuretic peptide; BUN, blood urea nitrogen; Cr, creatinine.

5 Minor Elevation of Cardiac Troponin I 343 고찰 ESC/ACC 기준에의한심근경색진단에서는민감한 troponin 을기준으로적용하기때문에기존 WHO 기준에의해진단되었을때보다심근경색진단빈도가증가하게된다 [13-15]. 이는예후가불량한고위험군을미리분류할수있게하여보다적절하고효율적인치료를가능하게한다 [14]. ESC/ACC는 troponin 이검출될정도의심근손상을받았다면환자의예후가나쁠것이명확하므로허혈에의한심근괴사를그정도에관계없이심근경색으로재정의할것을제안하고있다 [1, 10]. ESC/ACC는또한정상인군의 99백분위수를기준치로권장하고있는데, 위양성을줄이고검사의비정밀성으로인한오진가능성을줄이기위하여이때의총 CV 값은 10% 미만이될것을권고하고있다 [1, 16]. 본연구에서산출한 ctni의 99 백분위수는 0.07 ng/ml, 10% CV 값은 0.10 ng/ml로 10% CV 값이 99백분위수보다높았다. 이에 10% CV 값인 0.10 ng/ml를본원심근경색의경계치로정하였다. 현재거의모든검사법들이 99백분위수에서 10% CV 한계를충족시키지못하고있으나최근들어보다민감한 troponin 검사법들이개발되고있으므로조만간급성심근경색경계치로 99백분위수를사용할수있을것이다 [10, 16, 17]. 심근경색의경계치를비교해보기위해 ROC 곡선분석에의한값을구하였다. 본원에서설정한값은 0.13 ng/ml로, 제조사에서제시한경계치인 0.60 ng/ml보다농도가상당히낮았는데이는심근경색의분류시차이가있고대상수가적은것이원인일수있다. ctni 0.13 ng/ml에서의급성심근경색진단의민감도는 90.9%, 특이도는 87.7% 였고, 음성예측도가높았으며 88.0% 의효율성을가진검사인것을확인하였다. 특이도가상대적으로낮았던것은 21명의위양성환자가포함되었기때문인데, 이환자들은부정맥 (6예), 호흡부전 (4예), 심부전 (3예), 뇌혈관질환 (3예), 외상 (2예), 심근염 (1예), 패혈증 (1예), 횡문근융해증 (1예) 등의질환을가지고있었다. Troponin은심근손상시증가하나그기전은구분할수없어심근경색뿐만아니라외상, 심부전, 심근염, 고혈압, 부정맥, 중증천식, 호흡부전, 패혈증, 뇌혈관질환, 횡문근융해증등에서도증가할수있다고하였다 [1-3]. 또한 heterophil 항체나자가항체, 면역치료, 예방접종, 수혈등이면역검사법에간섭을일으켜위양성을나타낼수도있다 [18]. Troponin이심근손상에민감하고특이적인검사이기는하나허혈성외의원인으로도증가할수있으므로임상증상과다른검사결과들을종합적으로고려할필요가있다. 허혈성심질환유무에따라여러심질환관련생화학검사결 과들을비교분석해본결과, 허혈성심질환군에서 ctni 최고치가유의하게높은것으로나타났고 (P=0.012) 특히 ctni 값이다른생화학검사들에비해허혈성심질환과관련성이높은것을알수있었다. ctni 최초치와 BNP도비록유의하지는않았으나허혈성심질환군에서높은경향을보였다. CK나 CK-MB 는비허혈성심질환군에서더높은경향을보여 ctni보다특이성이낮은것을확인할수있었고이는여러문헌에서확인할수있었다 [1, 2]. ctni 최초치에따라네군으로나누어급성심근경색, 허혈성심질환, 심혈관질환의빈도를비교했을때, 3군에서급성심근경색이 53.3%, 허혈성심질환 70.0%, 심혈관질환 86.7% 로 4 군과마찬가지로 1군, 2군에비해빈도가크게높은것을볼수있었다. 이는제조사에서제공한심근경색경계치인 0.6 ng/ml 미만의경도증가에해당하는값인 10% CV 값이나 ROC 곡선분석에의한경계치가중요한임상적의의가있다는것을보여주고있다. ctni가높은군일수록사망도증가하는것을볼수있었으나큰차이는보이지않았는데, 이는본연구의대상수가적고심질환이외의모든환자군을포함하였기때문인것으로생각된다. 많은연구들이 troponin이경도로증가하더라도불량한예후와관련이있다고보고하고있다 [4-6, 19-22]. Kontos 등 [19] 에따르면, ctni가상승할수록사망, 심근경색, 유의한질병의발생등이단계적으로증가하였다. 따라서소량의상승이라도예후적인의미가있다고볼수있으며비록정도에따라차이는있지만경도증가에도의의를두어증가정도를치료결정에고려해야한다고하였다. Gudmundsson 등 [4] 도급성심근경색경계치이하에서의 ctni의상승이사망률과주요심혈관합병증과유의한관계가있었다고하였다. 또한다른연구들에서는 troponin 이경도로증가한환자에서도조기의침습적인치료로큰임상적인이득을얻을수있다고보고하였다 [6, 23, 24]. ctni 최초치를네군으로분류하여다른심질환관련생화학검사결과들을비교한결과, CK, CK-MB, LD, BNP, BUN, Cr의농도가네군간에유의한차이를나타냈다. 또한 BUN, Cr 검사결과가대체적으로정상인것으로보아 ctni의증가가신질환에의한것이아님을확인할수있었다. ctni가증가할수록다른심장표지자인 CK, CK-MB, LD가증가하는양상을보였다. CK, CK-MB, LD는 3군에서제일높았는데, 4군의대상수가적고 3군에서도급성심근경색, 허혈성심질환, 심혈관질환자가다수포함되어있었기때문인것으로생각된다. 그러나다른요인에의한증가가능성도배제할수는없었다. BNP도 ctni 가증가함에따라증가하는소견을보여허혈성심질환과관련

6 344 정채림 조성은 홍기숙 있는표지자로보인다. 결론적으로 ctni의경도증가가급성심근경색, 허혈성심질환, 심혈관질환및 1개월후사망률의증가와유의한관계가있었다. 요약배경 : Cardiac troponin I (ctni) 는심근손상에대한민감도와특이도가높아심근허혈진단에가장선호되는표지자이다. 본연구에서는 ctni의급성심근경색의경계치를설정하고경도증가의임상적의의를분석하고자하였다. 방법 : 2006년 1월부터 3월까지이화여자대학교의과대학부속동대문병원을내원하여 ctni 측정을의뢰한 204명을대상으로하였다. ctni은 Dimension RxL (Dade Behring, USA) 을사용하여측정하였다. 본원 ctni의최저검출한계와 10% CV 값을산출하였고, 정상인군의 99백분위수와 ROC 곡선분석에의한심근경색경계치를구하였다. 결과 : 본원 ctni의최저검출한계는 0.00 ng/ml, 10% CV 값은 0.10 ng/ml이었고, 99백분위수값은 0.07 ng/ml이었다. ctni 최고치를기준으로한 ROC 곡선분석에의한급성심근경색의경계치는 ctni 0.13 ng/ml이었고이때의민감도는 90.9%, 특이도는 87.7%, 곡선아래면적 (AUC) 은 0.921이었다. ctni의최고치비교결과비허혈성심질환군에비해허혈성심질환군에서통계적으로유의하게높았다 (P<0.05). 상기참고치및경계치들을기준으로 ctni 최초측정치에따라전체대상을 0.05 ng/ml (1군), ng/ml (2군 ), ng/ ml (3군), 0.60 ng/ml (4군 ) 의네군으로분류하여변수들을비교한결과, ctni 농도가높은군일수록급성심근경색, 허헐성심질환, 심혈관질환의빈도및 1개월후사망률이유의하게증가하였다 (P<0.05). 결론 : ctni의경도상승이급성심근경색, 허혈성심질환, 심혈관질환및 1개월사망률증가와유의한관계가있었다. 참고문헌 1. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J 2000;21: Jaffe AS, Ravkilde J, Roberts R, Naslund U, Apple FS, Galvani M, et al. It s time for a change to a troponin standard. Circulation 2000; 102: Babuin L and Jaffe AS. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ 2005;173: Gudmundsson GS, Kahn SE, Moran JF. Association of mild transient elevation of troponin I levels with increased mortality and major cardiovascular events in the general patient population. Arch Pathol Lab Med 2005;129: Apple FS and Wu AH. Myocardial infarction redefined: role of cardiac troponin testing. Clin Chem 2001;47: Morrow DA, Cannon CP, Rifai N, Frey MJ, Vicari R, Lakkis N, et al. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-st elevation myocardial infarction: results from a randomized trial. JAMA 2001;286: Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-st-segment elevation myocardial infarction--2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002;106: Zarich SW, Bradley K, Mayall ID, Bernstein LH. Minor elevation in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values. Clin Chim Acta 2004;343: Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979;59: Apple FS, Wu AH, Jaffe AS. European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: how to use existing assays clinically and for clinical trials. Am Heart J 2002;144: Panteghini M. Present issues in the determination of troponins and other markers of cardiac damage. Clin Biochem 2000;33: Clinical and Laboratory Standards Institute. User demonstration of performance for precision and accuracy; approved guideline. Document EP15-A. Wayne, PA: Clinical and Laboratory Standards Institute Ferguson JL, Beckett GJ, Stoddart M, Walker SW, Fox KA. Myocardial infarction redefined: the new ACC/ESC definition, based on

7 Minor Elevation of Cardiac Troponin I 345 cardiac troponin, increases the apparent incidence of infarction. Heart 2002;88: Polanczyk CA, Schneid S, Imhof BV, Furtado M, Pithan C, Rohde LE, et al. Impact of redefining acute myocardial infarction on incidence, management and reimbursement rate of acute coronary syndromes. Int J Cardiol 2006;107: Kavsak PA, MacRae AR, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, et al. The impact of the ESC/ACC redefition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction. Am Heart J 2006;152: Panteghini M, Pagani F, Yeo KT, Apple FS, Christenson RH, Dati F, et al. Evaluation of imprecision for cardiac troponin assays at lowrange concentrations. Clin Chem 2004;50: Melanson SE, Morrow DA, Jarolim P. Earlier detection of myocardial injury in a preliminary evaluation using a new troponin I assay with improved sensitivity. Am J Clin Pathol 2007;128: Makaryus AN, Makaryus MN, Hassid B. Falsely elevated cardiac troponin I levels. Clin Cardiol 2007;30: Kontos MC, Shah R, Fritz LM, Anderson FP, Tatum JL, Ornato JP, et al. Implication of different cardiac troponin I levels for clinical outcomes and prognosis of acute chest pain patients. J Am Coll Cardiol 2004;43: Lindahl B, Diderholm E, Lagerqvist B, Venge P, Wallentin L. Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC Ⅱ substudy. J Am Coll Cardiol 2001; 38: Henrikson CA, Howell EE, Bush DE, Miles JS, Meininger GR, Friedlander T, et al. Prognostic usefulness of marginal troponin T elevation. Am J Cardiol 2004;93: Cook G, Taylor D, France M, Burrows G, Manning E, Lyratzopoulos G, et al. Survival among hospital in-patients with troponin T elevation below levels defining myocardial infarction. QJM 2005; 98: Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. J Am Coll Cardiol 1997;29: Morrow DA, Antman EM, Tanasijevic M, Rifai N, de Lemos JA, McCabe CH, et al. Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI- 11B substudy. J Am Coll Cardiol 2000;36:

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -