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1 원저 Korean Circulation J 2004;34(9): 심부전환자의기능수행능력평가시 NT-proBNP 의유용성 성균관대학교의과대학삼성서울병원내과학교실 김성해 김제상 백경기 양정채 성지동 전은석 이상훈 홍경표 박정의 Role of NT-proBNP in Evaluation of Functional Status in Congestive Heart Failure Sung Hea Kim, MD, Je Sang Kim, MD, Kyung Kee Baek, MD, Jeong-Chae Yang, MD, Jidong Sung, MD, Eun-Seok Jeon, MD, Sang Hoon Lee, MD, Kyung Pyo Hong, MD and Jeong Ey Park, MD Division of Cardiology, Samsung Medical Center, Seoul, Korea ABSTRACT Background and Objectives:NT-proBNP, a sensitive and specific marker of congestive heart failure (CHF), is also useful in monitoring the effectiveness of treatment and in predicting prognosis. However, the usefulness of NT-proBNP for measuring the functional capacity as a component of the quality of life (QoL) in patients with CHF remains to be discovered. The Korean Activity Scale/Index (KASI) is a Koreanized tool for measuring the functional capacity in patients with cardiac diseases during daily activities, thus representing the physical domain of the QoL. The purpose of this study was to evaluate the relationship between NT-proBNP and the KASI. Subjects and Methods:Between July, 2003 and September, 2003, the NT-proBNP levels were measured in 76 patients with CHF that visited the OPD or who were hospitalized. They were asked to fill out a selfadministered questionnaire, from which their KASI scores were obtained. NYHA Fc and Heart Failure scores were also obtained from a history taking and physical examination conducted by the investigator. Results: The level of NT-proBNP increased with increasing NYHA Fc (p<0.001 by Kruskall-Wallis test). The Spearman correlation coefficient between NT-proBNP and the KASI score was (p<0.001), which was higher than that between the HF and KASI scores (rho=-0.557, p<0.001). The level of NT-proBNP also had a positive correlation with the HF score (rho=0.706, p<0.001). Conclusion:The level of NT-proBNP has a strong negative correlation with the KASI score, reflecting the functional capacity during daily activities. This suggests that NT-proBNP is useful in measuring the functional capacity as an element of the QoL in patients with CHF. (Korean Circulation J 2004;34(9): ) KEY WORDS:Activity scale index;brain natriuretic peptides;heart failure. 서 심부전환자에서기능수행척도 (functional status) 논문접수일 :2004 년 6 월 21 일심사완료일 :2004 년 6 월 28 일교신저자 : 성지동, 서울강남구일원동 50 번지성균관대학교의과대학삼성서울병원내과학교실전화 :(02) 전송 :(02) sungjd@samsung.co.kr 론 는환자의운동능력, 전반적인상태또는질병의중증도를대변하는중요한변수중하나이다이제까지알려진기능수행척도평가방법으로는다음과같은방법들이있다. 1) 운동부하검사와산소소모량검사. 1-3) 2) New York Heart Association Functional Class 4) 나 Canadian Cardiovascular Society Functional Class 5) 등의범주형도구 894

2 3) DASI(Duke Activity Status Index) 6) 와 KASI (Korean Activity Scale/Index) 7) 등의연속형도구그중운동부하검사와산소소모량검사는정확하고신뢰할만한평가방법이지만시행하는것이번거롭고시간과비용이많이든다. 이러한문제로실제임상에서는환자의병력만청취하여환자의대략적인기능수행능력을평가하는 NYHA Fc나 CCS Fc 등의도구들이흔히사용된다. 하지만이러한도구들은정확성과신뢰성이높은편이아니며 Ⅰ, Ⅱ, Ⅲ, Ⅳ와같이연속된변수가아닌범주형의결과로나타나기때문에임상연구에서의사용은제한적일수밖에없다. 이를보안하기위해계발된것이 DASI 이다. DASI 는환자에게특정한활동의가능여부에따라가중치를부여하여합산하기때문에연속적변수로표현되며비교적편리하게구할수있다. KASI 는 DASI 를모델로국내에서개발된도구이다. 이전의연구에서 KASI score 는운동부하검사의운동시간과밀접한상관관계가있었으며실제연구에사용할수있는유용한도구임이검증되었다. 7) 위에서언급한검사와도구외에도심부전환자에서기능수행척도를평가할수있는검사로최근 BNP 와 NT-proBNP 가주목을받고있다. BNP 는심부전환자의진단에도움을주고, 질병의중증도와관련이있으며, 약물치료효과판정에도유용하다고알려져있다. 9-16) 최근몇몇연구에서 BNP 가안정화된심부전환자에서산소소모량검사와상관관계가있으며따라서기능수행능력평가에도움이될수있다는주장이제기되었다. 13)14) NT-proBNP 는 BNP 와마찬가지로심부전의진단과치료효과판정에유용하며재현성이좋고비용이저렴하여임상에많이이용되고있다 ) 그러나 NT-proBNP 와심부전환자의삶의질과의연관성에대해서는알려진바가없다. 삶의질과의연관성을알아보기위해서는심부전환자에서의삶의질을측정하는도구가필요하겠으나이에대한한국형도구의개발이이루어진바없으므로, 한국형의기능수행능력평가도구로서개발되었으며삶의질의요소중신체적활동능력을잘반영할것으로생각되는 KASI 를조사도구로하여이와 NT-proBNP 의연관성을알아보고자하였다. 또한심부전의중증도롤반영하는또다른지표인 Heart failure score 와 KASI 의연관성을같이알아봄으로써실험실지표인 NT-proBNP 가임상적징후들로평가된지표인 Heart failure score 보다심부전환 자의삶의질중의한요소인신체적활동능력을잘반영할것인지알아보고자하였다. 대상및방법 2003년 7월 1일부터 2003년 9월 30일까지심부전으로본원외래에방문하거나입원한환자중급성또는만성신부전의증거가없고, 호흡기계질환, 관절질환, 또는뇌졸중등심장질환외의질환으로인한운동능력장애는없는 76명을대상으로하였다. 모든환자에게 KASI 를이용하여기능수행능력을평가하였다. KASI 의각문항은일상생활, 스포츠와같은여가활동, 집안일, 성생활등환자의삶의질과밀접한관련이있는각측면으로부터선정된항목들에대하여질문하도록되어있으므로삶의질을측정하는데있어서중요한한요소인일상생활중의육체적활동의제한에대해잘평가할수있을것으로생각된다. 7)8) KASI 는일상생활의특정한활동수행가능여부를묻는 15개문항으로구성된자기기입식설문이며, 이를각환자에게시행하여각문항당정해진가중치를곱하여 KASI score 를산출하였다 (Table 1). KASI score 는최소 0점에서최고 76.8 Table 1. KSAI questionnaire and weight value KASI (Korean Activity Scale/Index) Questionnaire Weight 1 Going downstairs Yes No Going up a hill Yes No Slow walking Yes No Regular walking Yes No Rapid walking Yes No Carrying heavy thing Yes No 8.5 (about kg) 7 Climbing Yes No Running Yes No Shower Yes No Housework Yes No Sexual intercourse Yes No Light exercise Yes No 3.5 (ex: gymnastics, bowling, archery) 13 Regular exercise Yes No 5.5 (ex: tennis, badminton, golf) 14 Vigorous exercise Yes No 9.5 (ex: soccer, basketball, handball) 15 Dressing oneself Yes No

3 점으로점수가높을수록기능수행능력이우수함을의미한다. 또모든환자에서 KASI 시행과같은시점에서외래방문시또는입원당일이나다음날에말초혈액을채취하여화학발광면역법 (Elecsys 2010;Roche Diagnostics, USA) 에의해 NT-proBNP를측정하었다. NYHA Fc와 CHF score(framingham Heart Study) 는환자를진찰한순환기내과의사가병력청취와신체검진을통해구하였다. 또심초음파는입원환자의경우입원일부터 7일이내에, 외래환자의경우외래방문일로부터 3개월이내에시행하였다. 모든자료는평균값 ± 표준오차로표현하였고, 통계분석에는 SPSS11.0을이용하였다. KASI score 를제외한 NT-proBNP, HF score 두변수모두정규분포를이루지않아비모수검정법인 Spearman 상관계수를이용하여평가하였다. 또 NYHA Fc에따른각각의군의 KASI score, NTproBNP 가정규분포를이루지않아군간의차이는비모수검증법인 Kruskall-Wallis test 를이용하였다. p 값이 0.05 미만이면통계적유의성을인정하였다. 결과 76명의환자중남자는 43명 (56.6%) 여자는 33명이었다. 외래환자가 54명 (71.1%) 입원환자는 22명이었다. 평균연령은 58±15세였고 NYHA class Ⅰ;12 명, Ⅱ;43 명, Ⅲ;16 명, Ⅳ;5 명이었다. 평균수축기혈압은 132±12 mmhg, 맥박수는분당 75±18회였 으며, 복용중인약제로는이뇨제가 68% 로가장많았고 ACEI 혹은 ARB(62%), 베타차단제 (42%), digoxin (21%) 순이었다. 심부전의원인으로는판막성심부전이 21명 (27.6%) 으로많았고허혈성심부전과확장성심근병증에의한심부전이각각 20명 (26.3%), 17명 (22.4%) 이었다. 76명의환자중 65명에서심초음파를실시하였고이들의평균좌심실구출율은 44±17%, 평균수축기좌심실용적은 43±14 mm, 평균이환기좌심실용적은 58±14 mm이었다. 각 NYHA class 에따른평균좌심실구출율은 Ⅰ;55±12%, Ⅱ;45±17%, Ⅲ;42±16%, Ⅳ;28±12% 였다. 각 NYHA class 의평균 NT-proBNP 값은 Ⅰ;140±27.7, Ⅱ;1262± 262, Ⅲ;6019±1361, Ⅳ;13229±6049 pg/ml였고, 평균 KASI 점수는 Ⅰ;69.0±3.5, Ⅱ;44.3±2.5, Ⅲ;32.8±4.3, Ⅳ;12.0±5.6로, NYHA Class가높아질수록즉심부전이심할수록 NT-proBNP 는증가하고 (p<0.001), KASI score는유의하게낮아졌다 (p<0.001) (Table 2)(Fig. 1). NT-proBNP 는 KASI score 와는음의상관관계를 Table 2. NT-proBNP and KASI score according to NYHA Fc NYHA Fc NT-proBNP (pg/ml) KASI score I 00140± ±3.47 II 01262± ±2.52 III 06019± ±4.30 IV 13229± ±5.60 The level of NT-proBNP increased with increasay NYHA Fc (p<0.001), but KASI score decreased (p<0.001). NTproBNP: N-terminal pro-b-type natriuretic peptide, KASI: Korean Activity Scale/Index, NYHA Fc: New York Heart Association functional class KASI score BNP (pg/ml) I II III IV NYHA Fc 0 I II III IV NYHA Fig. 1. NT-proBNP and KASI score according to NYHA Fc. NT-proBNP: N-terminal pro-b-type natriuretic peptide, KASI: Korean Activity Scale/Index, NYHA Fc: New York Heart Association functional class, BNP: brain natriuretic peptide. 896 Korean Circulation J 2004;34(9):

4 5.0 고 찰 Log BNP KASI 0Hospitalized patient 0 OPD patient Fig. 2. Correlation between KASI score and NT-proBNP (Spearman correlation coeffecient=-0.730, p<0.001). KASI: Korean Activity Scale/Index, NT-proBNP: N-terminal pro-b-type natriuretic peptide, BNP: brain natriuretic peptide, OPD: the out-patient department. Table 3. Correlation between KASI score and NT-proBNP and heart failure score (rho=spearman correlation coeffecient) KASI score NT-proBNP Heart failure score KASI score (Rho) NT-proBNP (Rho) Heart failure score (Rho) All p< KASI: Korean Activity Scale/Index, NT-proBNP: N-terminal pro-b-type natriuretic peptide (rho=-0.730, p<0.001) 가지며 (Fig. 2), Heart failure score 또한 KASI score 와음의상관관계를보이고있으나 (rho=-0.557, p<0.001), NT-proBNP에비해서는다소상관계수가낮은경향을보이고있다. NTproBNP 와 Heart Failure Score 간에는양의상관관계가있었다 (rho=0.706, p<0.001)(table 3). 이를종합하면심부전이심해질수록 NT-proBNP 는증가하며, Heart Failure Score 는높아지며, KASI score 는감소함을알수있다. 하지만 NT-proBNP 는 KASI score 사이의음의상관관계가외래환자에선유의하였지만 (rho=-0.734, p< 0.001), 입원환자에서는음의상관관계를보이는경향이있었으나통계적으로유의하지않았다 (rho=-0.255, p=0.053). BNP(Brain Natriuretic Peptide) 는심실용적이나압력증가에반응하여심실에서분비되는호르몬으로좌심실수축기기능이저하되는경우에증가하며, 혈중농도는 NYHA Fc에따른호흡곤란의정도와비례하고심부전환자에서장기예후를반영하는지표로알려져있다. 8-16) 특히 NT-proBNP 는재현성이좋고비용이저렴하여심부전환자의진단과치료효과판정에많이이용된다 ) 최근몇몇연구에서 BNP 가최고산소섭취량과연관성을보여심부전환자에서기능수행능력을평가하는데유용할것으로보고하고있다. 13)14) 본연구에서도 NT-proBNP 는 NYHA Fc로평가한호흡곤란의정도가심할수록증가하여기존에발표된연구결과와잘일치하였다. 그러나, NT-proBNP 가객관적인운동능력지표와연관성이있다는사실과심부전환자의삶의질을반영할것인가하는것은다소다른문제라고볼수있다. 운동부하검사상운동가능시간또는최고산소섭취량등의객관적인운동능력지표와일상생활중의기능수행능력이밀접한관계를가질것은틀림없으나, 일상생활중의다양한활동들에대한수행능력을모두반영한다고보기는어렵다. 따라서, NT-proBNP 가심부전환자의삶의질을반영하는지를연구하기위해서는심부전에서의삶의질을측정하기위하여특화된측정도구가필요하겠으나, 국내에는이러한도구가없으므로삶의질중에서신체적활동정도를잘반영할것으로보이는 KASI 를이용하여 NTproBNP 와의연관성을조사하였다. KASI 는 Table 1 에서보는바와같이일상생활중의다양한활동에대한가능여부를질문한다. 본연구결과에서 NT-proBNP 는 KASI 와매우연관성이높으며이는 NT-proBNP 가심부전환자의삶의질을잘반영할가능성을시사한다고하겠다. 또한 NTproBNP 는주로의사가평가한객관적징후들로구성되어있는또다른심부전의중증도지표인 Heart Failure Score 보다 KASI 와의연관성이더높은것으로보인다. 이는 NT-proBNP 가 Heart failure score 보다삶의질을더잘반영한다는것을시사한다고볼수있다. 앞으로 NT-proBNP 와삶의질과의연관성을더연구하기위해서는심부전환자에게특화된삶의질도구 897

5 개발하여적용하는것이필요하다고하겠다. 하지만입원환자군에서 NT-proBNP 와 KASI score 의역상관관계가약했는데, 이는입원환자의숫자가적었던것이주된이유일것으로보이나, 또한 NT-pro- BNP 는채혈을통해이루어지는객관적인검사인반면 KASI score 는자기기입식설문을통한주관적검사이기때문에나타난현상으로생각된다. 즉외래를방문하는안정화된심부전환자는기능수행능력의최근변화가없는상태이므로설문에대한답변의신뢰성이높은반면, 입원환자의경우설문을작성시과거안정시의기능수행능력에비해최근악화시의기능수행능력은훨씬낮은상태이므로, 과거안정시의상태를기준으로답변을하게된다면답변의정확성이떨어질가능성이있다. 따라서최근급격한변화를겪은입원환자에서는 KASI score 가환자의현재의기능수행능력을충분히반영하지못할수있다. 본연구는몇가지의제한점을가지고있는데, 3차병원의환자를대상으로이루어졌으며, 대상의크기가비교적작아연령대가다르거나다른임상적특성을가지는집단에적용할경우주의를요할것이다. 또한 KASI 가설문을통해얻어지기때문에문맹률이높거나학력이낮은환자군에서는응답률과정확도가현저히낮아질수있다는기본적인한계를지니고있다. 이럴경우 KASI 를자기기입식이아닌설문조사자가직접개입하여조사하는방식으로전환할경우정확도를높힐수있을것으로기대되나이에대해서는검증된바가없다. 또한 KASI 는심혈관계질환환자전반에서사용될의도로개발된범용도구로심부전환자에특화되어개발된도구가아니라는점도제한점이될수있을것이다. 결론적으로 NT-proBNP 는 Heart Failure Score 와같이기존에알려져있는지표보다심부전환자에서삶의질요소중신체적기능수행정도를평가하는데유용할것으로사료된다. 심부전환자의삶의질을측정하는특화된도구가향후개발된다면이를이용하여본연구결과를추시함으로써 NT-proBNP 의유용성을확인할필요가있을것이다. 요약 배경및목적 : NT-proBNP 는심부전환자의진단에도움을줄뿐 898 아니라질병의중증도와관련이있으며약물치료효과판정에도유용하다고알려져있으나심부전환자의삶의질과의연관성에대해서는알려진바가없다. 최근삶의질의여러요소중신체적기능수행능력을정확히평가하고자 Duke Activity Status Index를모델로 Korea Activity Scale/Index(KASI) 가계발되었고, 본논문에서는 NT-proBNP 와 KASI 의연관성을통해심부전환자에서기능수행능력평가시 NT-proBNP 의유용성에대해알아보고자한다. 방법 : 심부전으로진단받은외래환자또는입원환자 76명을대상으로일상생활의특정한활동수행가능여부를묻는 15개문항으로구성된자기기입식설문조사를시행하였고각문항당정해진가중치를부여하여 KASI Score 를산출하였다. NT-proBNP 는화학발광면역법에의해측정되었고 NYHA class와 CHF score 는설문시행자가병력청취와신체검진을통해얻어졌다. 결과 : 76명의환자중남자는 43명 (56.6%), 연령은 58± 15세, NYHA class Ⅰ;12명, Ⅱ;43명, Ⅲ;16명, Ⅳ;5 명이었다. 각 NYHA class 의평균 NT-proBNP 값은 Ⅰ;140, Ⅱ;1262, Ⅲ;6019, Ⅳ;13229 pg/ ml였다. NT-proBNP 와 HF score 와의 Spearman 상관계수는 로유의하였고 (p<0.05), NT-proBNP 와 KASI score 와의 Spearman 상관계수는 (p<0.001) 로 HF score 와 KASI score 의상관계수 (p<0.001) 보다높았다. 결론 : NT-proBNP 는일상생활중의기능수행능력을반영하는 KASI 와연관성이높았으며, 심부전환자에서삶의질요소중신체적기능수행정도를평가하는데유용할것으로생각된다. 중심단어 :NT-proBNP;Korean Activity Scale/Index; 심부전. REFERENCES 1) Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, Smith R, Fletcher R. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. Circulation 1993;87:VI ) Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Korean Circulation J 2004;34(9):

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon