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1 Biomedical Science Letters 2018, 24(3): 245~252 eissn : Original Article Heart Rate Recovery in Metabolically Healthy Obesity and Metabolically Unhealthy Obesity Korean Adults Kyung-A Shin,* Department of Clinical Laboratory Science, Shinsung University, Dangjin 31801, Korea Heart rate recovery (HRR) is simply an indicator of autonomic balance and is a useful physiological indicator to predict cardiovascular morbidity and mortality. The purpose of this study was to compare the differences in HRR between metabolically healthy obesity group and metabolically unhealthy obesity and to ascertain whether heart rate recovery is a predictor of metabolic syndrome. Metabolic syndrome was defined according to the standards of the National Cholesterol Education Program Adult Care Panel III. Obesity was assessed according to WHO Asian criteria. It was classified into three groups of metabolically healthy non-obesity group (MHNO, n=113), metabolically healthy obesity group (MHO, n=66), metabolically unhealthy obesity (MUO, n=18). Exercise test was performed with Bruce protocol using a treadmill instrument. There was no difference in HRR between MHO and MUO (32.71±12.25 vs 25.53±8.13), but there was late HRR in MUO than MHNO (25.53±8.13 vs 34.51±11.80). HRR in obese was significantly correlated with BMI (r=-0.342, P=0.004), waist circumference (r=-0.246, P=0.043), triglyceride (r=-0.350, P=0.003), HbA1c (r=-0.315, P=0.009), insulin (r=-0.290, P=0.017) and uric acid (r=-0.303, P=0.012). HRR showed a lower prevalence of abdominal obesity, hypertriglyceridemia, and low HDL-cholesterol in the third tertile than in the first tertile. In conclusion, MHO had no difference in vagal activity compared with MHNO, but MUO had low vagal activity. HRR is associated with metabolic parameters and is a useful predictor of abdominal obesity, hypertriglyceridemia, and low HDL-cholesterolemia Key Words: Heart rate recovery, MHO, MUO 서론자율신경계기능장애는비만을포함한대사증후군구성요소및심폐체력과관련이있는심혈관계위험인자이다 (Bjelakovic et al., 2017). 또한교감신경의활성증가와부교감신경의활성도감소에따른자율신경계조절능력의저하는대사이상을예측한다고보고된다 (Berntson et al., 2008; Licht et al., 2013). 심박수회복 (heart rate recovery, HRR) 은간단하게자율신경계균형을검증하는지표이며, 심혈관질환의이환율및사망률을예측하는데유용한생 리적지표이다 (Peçanha et al., 2014; Yu et al., 2016). 심박수회복은운동직후의자율신경계변화를반영하며, 최대심박수와운동후 1분대심박수의차이로정의되는부교감신경재활성도를나타낸다 (Shetler et al., 2001; Kim et al., 2011). 또한대사증후군은자율신경계기능장애와함께심혈관질환위험을증가시키는요인으로제시되며, 국내에서성인을대상으로파악한대사증후군유병률은 1998년 24.9% 에서 2007년에는 31.3% 로증가하는추세를보인다 (Curtis and O'Keefe, 2002; Libby et al., 2002; Lim et al., 2011). 대사증후군의심박수회복에대한 Shin (2011) 의연구결과에따르면 30세이상성인을대상으로대사증후군위험 Received: June 7, 2018 / Revised: July 11, 2018 / Accepted: September 7, 2018 * Professor. Corresponding author: Kyung-A Shin. Department of Clinical Laboratory Science, Shinsung University, 1 Daehak-ro, Jeongmi-myeon, Dangjin 31801, Korea. Tel: , Fax: , mobitz2@hanmail.net C The Korean Society for Biomedical Laboratory Sciences. All rights reserved. CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

2 요인이없는군보다대사증후군진단군에서늦은심박수회복을보인다고보고하였으며, 유사하게 Singh과 Shen (2013) 은청소년을대상으로정상체중보다과체중청소년에서미주신경활성도의감소로인해심박수회복이느리다는결과를제시하였다. 반면마른체형과비만체형의최대운동후심박수회복과심박동수변이 (heart rate variability) 에는차이가없다는일관되지않은결과가보고된다 (Guilkey et al., 2017). 한편, 체질량지수 (body mass index, BMI) 를기준으로과체중이나비만인은이상지질혈증, 고혈압및당뇨병과같은대사합병증의유병율이높으나, 모든과체중과비만인에서대사적으로이상을나타내는것은아니다 (Grundy, 2004; Dorresteijn et al., 2012). 과체중또는비만인의 18~ 44% 는인슐린감수성이높고당뇨병, 이상지질혈증, 고혈압, 낮은염증및간효소치를보여이러한사람을대사적으로건강한비만인 (metabolically healthy obesity, MHO) 이라고규정하고있다 (Primeau et al., 2011). 하지만비만인에서느린심박수회복을보이는것에대한명확한증거는부족하며, 국내에서는대사적으로건강한비만군과대사적으로이상이있는비만군을구분하여심박수회복과의관계를확인한연구는제한적이다. 또한아시아인은백인과비교하여 BMI가낮지만심혈관질환의발생위험은더높은것으로보고되고있어서구인을대상으로한연구결과를국내에적용하기에어려움이있다 (Deurenberg et al., 1998). 본연구의목적은대사적으로건강한비만군과대사적으로이상이있는비만군간에자율신경계이상을간단하게검증할수있는지표인심박수회복의차이를비교하고심박수회복이대사증후군발병을예측하는지표인지를확인하고자하였다. 재료및방법연구대상자및대사증후군진단기준본연구의대상자는 2016년 3월부터 2018년 3월까지경기소재일개종합병원종합검진센터에서운동부하검사를받은 20세이상의성인을연구대상으로하였다. 전체대상자 210명중심박수에영향을미치는약제를복용중인자, 신체계측치및혈액검사수치가누락된자, 외국인대상자를제외한최종연구에포함된대상자는 197명이었다. 복용중인약제에대한정보는자기기입식설문지를통해얻었으며, 본연구는경기소재종합병원에서 기관생명윤리위원회의심의를받아시행되었다. 대사증후군은 NCEP-ATP III (Executive Summary of The Third Report of The National Cholesterol Education Program Adult Treatment Panel III) 기준에따라 5가지항목중 3가지이상해당하는경우대사적으로이상이있다고판정하였다 (National Cholesterol Education Program-Adult Treatment Panel III, 2001). 대사증후군진단기준중복부비만은아시아인의기준을적용하였다 (WHO, 2000). 또한세계보건기구에서제시한아시아인의기준에따라 BMI 25 kg/m 2 인경우비만으로판정하였으며, 정상체중은 18.5~22.9 kg/m 2 로정의하였다 (WHO, 2000). 이상의대사증후군과비만의정의에따라대사적으로건강한정상체중군 (metabolically healthy nonobesity, MHNO, n=113), 대사적으로건강한비만군 (metabolically healthy obesity, MHO, n=66), 대사적으로이상이있는비만군 (metabolically unhealthy obesity, MUO, n=18) 으로집단을분류하였다 (Oh et al., 2006). 신체계측및혈액검사 DS-103M (Jenix, Seoul, Korea) 자동신체계측기를사용하여신장과체중을계측하였으며, BMI는체중 (kg) / { 신장 (m 2 )} 로계산하여제시하였다. 허리둘레는양발을 25~ 30 cm 정도벌리고숨을내쉰상태로갈비뼈가장아래부분과골반의가장높은위치인장골능의중간부위를줄자로측정하였다. 엉덩이둘레는엉덩이의가장돌출된지점을지나수평으로측정하였고허리둔부비 (waist to hip ratio, WHR) 는허리둘레를엉덩이둘레로나눈값으로하였다. 혈압은 10분정도안정을취한후수은혈압계 (HICO, Tokyo, Japan) 로 10분간격으로 2회측정하여평균값을적용하였다. 혈액분석은 8시간이상공복후전주정맥 (antecubital vein) 에서채혈하여총콜레스테롤, 중성지방, HDL-콜레스테롤, LDL (low density lipoprotein)-콜레스테롤, 공복혈당, 요산, 고감도 C-반응단백 (high sensitivity C- reactive protein, hs-crp), 호모시스테인을자동생화학분석기 TBA-200FR NEO (Toshiba, Tokyo, Japan) 로측정하였다. 당화혈색소 (hemoglobin A1c, HbA1c) 는 Variant II (Bio-Rad, CA, USA) 로 HPLC (high performance liquid chromatography, HPLC) 법으로측정하였다. 인슐린은 Modular Analytics E170 (Roche, Mannheim, Germany) 장비로 ECLIA (electrochemiluminescence immunoassay) 의원리로검사하였으며, 모든혈액검사는경기소재종합병원진단검사의학과에서직접분석하였다

3 운동부하검사운동부하검사는 treadmill (Medtrack ST 55, Quinton Instrument Co., USA) 기구로 Bruce protocol 에따라증상제한성 (symptom limited) 운동부하를시행하였다. Bruce protocol 은 3분간격으로회전속도와경사도에의해운동단계별 (stage) 부하량을증가시키는방법이다. 운동직전과운동중 3분간격으로심전도, 혈압, 심박수를기록하였으며, 운동후회복기는 1분, 3분, 5분대에심전도, 혈압, 심박수를측정하였다. 운동부하검사중심박수와심전도측정은 12 채널 Quinton stress test system (Q4500, Quinton Instrument Co., USA) 으로측정하였으며, 220에서검사자의나이를뺀최대심박수의 85~90% 이상도달할때까지운동부하검사를시행하였다. 또한운동강도는대사당량 (metabolic equivalents, MET) 으로구하였으며, treadmill 속도와경사도 를이용하여구하였다. 운동후회복기반응은 treadmill 경사도 0%, 속도 1.3 mph로하여 30~40초간걷게하고, treadmill이완전히정지한다음침대에누워 5분동안심전도, 혈압, 심박수의회복반응을기록하였다. 심박수회복 (heart rate recovery, HRR) 은운동부하검사시도달한최대심박수에서 1분대회복기심박수를뺀값으로계산하였다 (Cole et al., 1999). 최대심박수및혈압은운동시, 회복기동안에가장높은심박수및혈압으로정의하였다. 자료처리방법통계분석은 SPSS Windows 21.0 (IBM, Armonk, USA) 프로그램으로분석하였다. MHNO, MHO, MUO군의세집단간인체측정변인, 생화학적변인및심박수회복을포함한운동부하검사에따른혈역학적반응의차이를확인하기위해일원분산분석 (one-way ANOVA) 을시행하였으며, Table 1. Anthropometric and biochemical characteristics of the study subjects according to obesity phenotype Variables MHNO (n=113) MHO (n=66) MUO (n=18) P-value Age (years) 46.30± ± ± Sex (male, %) 72 (63.7) 55 (83.3) 14 (77.8) Height (cm) ± ± ± Weight (kg) 60.58± ±10.30 * 81.50±10.91 * <0.001 BMI (kg/m 2 ) 21.99± ±2.04 * 28.72±2.53 * <0.001 WC (cm) 76.95± ±6.26 * 93.88±6.72 * <0.001 HC (cm) 91.52± ±3.93 * ±8.03 * <0.001 WHR 0.85± ±0.04 * 0.95±0.05 * <0.001 SBP (mmhg) ± ±14.19 * ±13.51 * <0.001 DBP (mmhg) 71.32± ±9.29 * 82.50±11.66 * <0.001 TC (mg/dl) ± ±37.99 * ± TG (mg/dl) ± ± ± * <0.001 HDL-C (mg/dl) 55.36± ± ±11.35 * LDL-C (mg/dl) ± ±34.31 * ±31.06 <0.001 Glucose (mg/dl) 92.01± ± ±24.04 * <0.001 HbA1c (%) 5.71± ± ±0.81 * <0.001 Insulin (µu/ml) 4.74± ±4.07 * 10.69±6.10 * <0.001 Uric acid (mg/dl) 5.17± ±1.30 * 6.15±1.36 * hs-crp (mg/dl) 0.16± ± ± Homocysteine 12.09± ± ± Calculated by one way ANOVA and Scheffe test. Values are presented as mean ± SD. * Significantly different from MHNO at P<0.05, Significantly different from MHO at P<0.05. Calculated by χ 2 -test. Data are presented as number (%). Abbreviation: MHNO, metabolically healthy non obesity; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; BMI, body mass index; WC, waist circumference; HP, hip circumference; WHR, waist hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HbA1c, hemoglobin A1c; hs-crp, high sensitivity C-reactive protein

4 사후검정은 Scheffe 검정방법을적용하였다. 또한카이제곱검정 (chi-square test) 을통해세집단간성별에차이가있는지를확인하였다. 심박수회복과대사증후군관련지표들간의관련성을알아보기위해성별과연령을보정한후상관관계 (correlation coefficient) 분석을시행하였으며, 심박수회복을삼분위수로나누어대사증후군및대사증후군구성요소의발병위험을알아보기위해성별과연령을보정한후로지스틱회귀 (logistic regression) 분석을실시하였다. 모든통계적유의수준은 P<0.05로정하였다. (P=0.001). HDL-콜레스테롤은 MHNO군보다 MUO군이낮았으며 (P=0.001), hs-crp와호모시스테인은집단간차이가없었다. 집단간운동부하검사에따른혈역학적반응집단간운동부하검사에따른혈액학적반응의차이를비교한결과운동지속시간은 MHNO군과 MHO군보다 MUO군이낮게나타났으나 (P=0.047), MET는집단간차 결 과 집단간인체측정및생화학적지표 이연구에서는대상자를 MHNO, MHO, MUO군으로분류하여집단간인체측정및생화학적지표의차이를비교한결과 Table 1과같다. 연령은집단간차이가없었으나, 성별은 MHNO, MHO, MUO 세집단간차이가있었다 (P=0.016). 체중, BMI, 허리둘레, 엉덩이둘레는 MHNO 군보다 MHO군과 MUO군이높았으며, MUO군은 MHO 군보다높았다 ( 모두 P<0.001). WHR, 수축기와이완기혈압은 MHNO군보다 MHO군과 MUO군이높았다 ( 모두 P< 0.001). 총콜레스테롤 (P=0.004) 과 LDL-콜레스테롤 (P<0.001) 은 MHNO군보다 MHO군이높았다. 중성지방, 공복혈당, HbA1c는 MHNO군과 MHO군보다 MUO군이높았다 ( 모두 P<0.001). 인슐린은 MHNO군보다 MHO군과 MUO군이높았으며, MUO군은 MHO군보다높았다 (P<0.001). 요산은 MHNO군보다 MHO군과 MUO군에서높게나타났다 Fig. 1. Difference of HRR of MHNO, MHO and MUO groups MHNO (34.51±11.80), MHO (32.71±12.25), MUO (25.53±8.13). * Significantly different from MHNO at P<0.05. Abbreviation: MHNO, metabolically healthy non obesity; MHO, metabolically healthy obesity; MUO, metabolically abnormal obesity; HRR, heart rate recovery. Table 2. Exercise capacity and haemodynamic parameters of the study subjects according to obesity phenotype Variables MHNO (n=113) MHO (n=66) MUO (n=18) P-value Exercise duration (min) 9.89± ± ±1.39 * Exercise capacity (MET) 11.96± ± ± Rest HR (beats/min) 63.52± ± ± Rest SBP (mmhg) ± ±14.39 * ±12.84 * Rest DBP (mmhg) 72.89± ± ±11.05 * Max HR (beats/min) ± ±17.62 * ±13.70 * Max SBP (mmhg) ± ±24.11 * ±25.19 * Max DBP (mmhg) 79.40± ± ± Calculated by one way ANOVA and Scheffe test. Values are presented as mean ± SD. * Significantly different from MHNO at P<0.05, Significantly different from MHO at P<0.05. Abbreviation: MHNO, metabolically healthy non obesity; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; obesity; MHO, metabolically healthy obesity; MUO, metabolically abnormal obesity; MET, metabolic equivalents; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; HRR, heart rate recovery

5 이가없었다. 안정시수축기혈압 (P=0.009) 과최대심박수 (P=0.001), 최대수축기혈압 (P=0.005) 은 MHNO군보다 MHO군과 MUO군이높았으며, 안정시이완기혈압은 MHNO군과 MHO군보다 MUO군이높았다 (P=0.001) (Table 2). 또한심박수회복은 MUO군보다 MHO군이높은경향을보였으나통계적유의성은없었으며, MHNO군보다 MUO군이낮게나타났다 (P=0.009) (Fig. 1). 비만군에서심박수회복과대사증후군관련지표들간의상관성 연령과성별을보정한후비만군에서심박수회복과대사증후군관련지표들간의상관관계를분석한결과 BMI (r=-0.342, P=0.004), 허리둘레 (r=-0.246, P=0.043), HbA1c (r=-0.315, P=0.009), 인슐린 (r=-0.290, P=0.017), 요산 (r=- Fig. 2. Age and gender adjusted correlations between the heart rate recovery and triglyceride in obese. Abbreviation: TG, triglyceride; HRR, heart rate recovery , P=0.012), 중성지방 (r=-0.350, P=0.003) 은심박수회복과유의한역상관관계를나타냈다 (Table 3) (Fig. 2). 심박수회복삼분위수에따른대사증후군및대사증후군구성요소의발병위험 연령과성별을보정한후심박수회복삼분위수에따른대사증후군및대사증후군구성요소에대한교차비 (odds ratio) 와 95% 신뢰구간 (confidence interval, CI) 을 Table 4에제시하였다. 증가된허리둘레는심박수회복의제1삼분위수보다제3삼분위수에서 0.27배 (95% CI: 0.103~0.690), 높 Table 3. Age and gender adjusted correlations the heart rate recovery and metabolic parameters in obese Metabolic parameters HRR (beats) Correlation coefficient P-value BMI (kg/m 2 ) WC (cm) SBP (mmhg) DBP (mmhg) TC (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) Glucose (mg/dl) HbA1c (%) Insulin (µu/ml) Uric acid (mg/dl) Abbreviation: HRR, heart rate recovery; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HbA1c, hemoglobin A1c. Table 4. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of the HRR associated with metabolic syndrome components Metabolic parameter HRR (beats) 1 st Tertile 2 nd Tertile 3 rd Tertile Large waist circumference 1.00 (Reference) (0.222~1.187) (0.103~0.690) * High triglyceride level 1.00 (Reference) (0.306~1.405) (0.145~0.773) * Reduced HDL-C 1.00 (Reference) (0.285~1.508) (0.126~0.852) * Increased blood pressure 1.00 (Reference) (0.214~1.255) (0.288~1.599) Elevated fasting blood sugar 1.00 (Reference) (0.284~2.222) (0.201~1.813) Metabolic syndrome 1.00 (Reference) (0.079~1.400) (0.351~3.344) Adjusted odds ratios for metabolic components and metabolic syndrome. Adjusted for age and gender. * ; P<0.05. Abbreviation: HRR, heart rate recovery; HDL-C, high density lipoprotein cholesterol

6 은중성지방은심박수회복제1삼분위수보다제3삼분위수에서 0.34배 (95% CI: 0.145~0.773) 낮은유병률을나타냈다 (P<0.005). 또한낮은 HDL-콜레스테롤은심박수회복의제1삼분위수보다제3삼분위수에서 0.33배 (95% CI: 0.126~ 0.852) 낮은유병률을보였다 (P<0.005). 고찰한국성인을대상으로한이연구결과 MHO군은 MHNO 군과비교하여미주신경활성도에차이가없었으나, MUO 군은늦은심박수회복을보여미주신경활성도가낮았다. 심박수회복은 BMI, 허리둘레, 중성지방, HbA1c, 인슐린, 요산과역상관관계를보였다. 또한심박수회복은대사증후군구성요소중복부비만, 고중성지방혈증, 낮은 HDL- 콜레스테롤혈증을예측하는유용한지표임을확인하였다. 대사적으로건강한비만인은대사적으로이상이있는비만인에비해높은인슐린감수성과고혈압, 이상지질혈증, 염증반응등대사적이상의발생빈도가낮은것으로알려져있다 (Primeau et al., 2011). 특히교감신경의활성도증가와부교감신경의활성화감소에의한자율신경계기능장애는비만인에서자주발견되며인슐린저항성, 중심성비만, 시상하부의염증, 심폐체력저하의결과로추정되고있다 (Rodríguez-Colón et al., 2011; Zhu et al., 2016; Jais and Brüning, 2017). 자율신경계및심혈관계기능의평가는심박동수변이및압력수용체민감도 (baroreceptor sensitivity) 로추정할수있으나, 측정의간편성때문에심박수회복을흔히사용한다 (Cole et al., 1999). 운동선수나건강인은운동후심박수회복반응이빠르게나타나며, 느린심박수회복은고혈압, 당뇨병및심혈관질환의위험을예측하는지표로제시된다 (Imai et al., 1994; Cole et al., 1999; Nishime et al., 2000). 본연구결과 MHO군과 MUO군간에심박수회복은차이가없었으나, MHNO군보다 MUO군에서늦은심박수회복반응을나타냈다. 이는대사증후군을동반한비만성인에서심박수회복으로평가된자율신경기능장애가존재함을암시하는결과이다. 또한비만인에서심박수회복은대사지표중 BMI, 허리둘레, 중성지방, HbA1c, 인슐린, 요산과유의한역상관관계를보였다. 최근연구에서심박수회복의감소는 BMI가높을수록영향을받으며, 대사적으로건강한비만아동보다대사적으로이상이있는비만아동에서심박수회복으로평가한자율신경계기능장애가존재함을확인하였다 (Bjelakovic et al., 2017). 또한 MHO군은 MUO군과비교하여심혈관계질환및사망위험이낮으며, MHNO군과비교하여도위험이높지않은것으로보고된다 (Phillips, 2013; Stefan et al., 2013; Blüher, 2014; Samocha-Bonet et al., 2014). 또다른연구에서는 MHO군에서현저하지는않으나잠재적인심혈관질환위험과대사장애를내포하고있어체중만으로건강상태를파악하는것의부적합성을보고하였다 (Hong et al., 2012; Shin et al., 2017). 이러한결과들을종합하면비만하더라도대사적상태에따라비만의중재적접근을달리해야하며, 잠재적인심혈관계를평가하는데비만상태뿐만아니라대사적이상유무를동시에고려하는것이중요함을의미한다. 그러나피험자의건강상태는 MHO군에서 MUO 군으로전환될수있으며, 그반대도전환될수도있다. 예컨대, Soriguer 등 (2013) 은 6년간의추적관찰결과 MHO 의 30~40% 가 MUO로전환된것을확인하였다. Adelaide Health Study에서는 5.5~10.3년의추적관찰기간동안 MHO 표현형을보였던개인의약 1/3이 MUO 표현형으로전환되어 MHO 표현형은정적인상태가아니라는것을증명하였다 (Appleton et al., 2013). 본연구에서심박수회복은제1삼분위수보다제3삼분위수에서복부비만, 고중성지방혈증, 낮은 HDL-콜레스테롤혈증의유병률이낮게나타나심박수회복이대사증후군구성요소중복부비만, 고중성지방혈증, 낮은 HDL-콜레스테롤혈증을예측하는유용한지표임을확인하였다. 자율신경계기능장애는심혈관계위험증가및사망률과관련이있으므로심혈관계위험을평가하기위해서는비만인의심박수회복을측정함으로써자율신경계기능을정량화할필요성이있겠다 (Bjelakovic et al., 2017). 그러나이러한목적을위해서는심박수회복을평가하는프로토콜의표준화와표적장기손상의위험을예측하는심박수회복의적정절단값에대한검토가요구된다 (Bjelakovic et al., 2017). 본연구는횡단면연구로인과관계를규명하는데어려움이있으며, 가족력, 음주, 흡연, 운동습관등의자료부족으로연구에서고려하지못하였다. 그러나본연구는한국인을대상으로비만표현형에따른심박수회복반응의차이와심박수회복과대사지표간의관련성및심박수회복의대사증후군예측능력을확인한연구로의미가있겠다. ACKNOWLEDGEMENTS None

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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 - -