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Original ORIGINAL Article ARTICLE Korean Circulation J 2005;35:436-442 ISSN 1738-5520 c 2005, The Korean Society of Circulation 아포지단백 B 와콜레스테롤지표사이의일치 / 불일치 성균관대학교의과대학강북삼성병원내과학교실, 1 산업의학교실 2 황상태 1 김병진 1 김은란 1 신헌섭 1 성기철 1 김범수 1 강진호 1 이만호 1 박정로 1 유승호 2 Concordance/Discordance between Apolipoprotein B Levels and the Cholesterol Indexes Sang Tai Hwang, M.D. 1, Byung Jin Kim, M.D. 1, Eun Ran Kim, M.D. 1, Hun Sub Shin, M.D. 1, Ki Chul Sung, M.D. 1, Bum Soo Kim, M.D. 1, Jin Ho Kang, M.D. 1, Man Ho Lee, M.D. 1, Jung Ro Park, M.D. 1 and Seung Ho Ryu, M.D. 2 1 Department of Internal Medicine and 2 Occupational Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea ABSTRACT Background and Objectives:Apolipoprotein B (Apo-B) has been reported to be a better predictor of the coronary artery disease (CAD) than the cholesterol indexes. The aim of this study was to examine the concordance/discordance between the apolipoprotein B levels and the cholesterol indexes, and to assess the factors affecting the discordance. Subjects and Methods:A total of 11,816 participants (6,965 men and 4,851 women) were enrolled in this study from all the individuals who participated in medical screening examinations at the health promotion center in Kangbuk Samsung Hospital from January to December 2002. All the participants had no history of coronary artery disease. We assessed the concordance between the biochemical parameters of the atherogenic indexes, and we evaluated the factors affecting the discordance. Results:Despite the fact that the Apo-B and the various cholesterol indexes were highly correlated, the concordance rate was merely 47-56%. Multinomial logistic regression analysis showed the possibility of an increased risk for the group of discordance in whom Apo-B level was disproportionately higher than LDL cholesterol in the elderly, the smokers, the men and the people having a larger waist circumference, a lower total cholesterol level, a higher triglyceride level and a higher HDL-C level. Conclusion:The measurement of apo B, along with the measurement of the standard lipid profile, could be a great help in evaluating the CAD risk and for aiding in the treatment of dyslipidemia in the elderly, the smokers, men and the people having a larger waist circumference, a lower total cholesterol level, a higher triglyceride level and a higher HDL-C level. (Korean Circulation J 2005;35:436-442) KEY WORDS:Apolipoprotein B;LDL Cholesterol. 서 저밀도지단백콜레스테롤은심혈관질환의주요위험인자로서콜레스테롤강하치료의기준이되어왔다. 1) 하지만 론 논문접수일 :2004 년 11 월 22 일수정논문접수일 :2005 년 3 월 14 일심사완료일 :2005 년 04 월 06 일교신저자 : 김병진, 110-746 서울종로구평동 108 번지성균관대학교의과대학강북삼성병원내과학교실전화 :(02) 2001-2450 전송 :(02) 2001-2049 E-mail:bjjake.kim@samsung.com 초저밀도지단백콜레스테롤, 중밀도지단백콜레스테롤, 고밀도지단백콜레스테롤, 그리고아포지단백등도동맥경화에영향을준다는것이밝혀짐에따라저밀도지단백콜레스테롤외의다른지질들에대한연구들이진행되어왔다. 2) 2001 년발표된 Third report of National Cholesterol Education Program(NCEP) Adult Treatment Panel(ATP) Ⅲ에서는저밀도지단백콜레스테롤 (LDL-C) 의증가를심혈관질환의주요위험요인으로하고저밀도지단백콜레스테롤을낮추는것을치료의제1목표로하였고이전과달리고중성지방혈증 (200 mg/dl 중성지방 <500 mg/dl) 이있 436

Sang Tai Hwang, et al:concordance/discordance between Apo-B Level and Cholesterol Index 437 는경우비고밀도지단백콜레스테롤과아포지단백 B 사이에강한연관성이있어아포지단백 B의측정을대체하여비고밀도지단백콜레스테롤의기준을추가하였다. 1) 하지만최근혈중아포지단백 B의농도및아포지단백 B/A1 의비가동맥경화의위험요소로서향후심혈관질환의위험을예측하는데더효과적이라는연구결과들이보고되어짐에따라, 동맥경화성입자의총수를대변하는아포지단백의중요성이부각되었다. 2-7) 또한국내에서도관동맥질환과아포지단백과의연관성에대한연구들이보고된바있지만 8-10) 여러콜레스테롤지표들과아포지단백과의일치도에대한국내보고는없는실정이다. 이에저자들은실제대부분의임상에서콜레스테롤강하요법의기준이되는혈중저밀도지단백콜레스테롤농도및여러콜레스테롤지표들과아포지단백사이의일치도와연관성을평가하고관동맥질환의위험인자들에따른차이를알아보고자하였다. 대상및방법 대상 2002 년 1월부터 12월까지강북삼성병원에서종합건강검진을받은수진자중관동맥질환의기왕력이없는 11,816 명 ( 남자 6,965 명, 여자 4,851 명 ) 을대상으로하였다. 방법모든참여자들은설문지와인터뷰를통해당뇨병, 고혈압, 심혈관질환의과거력및가족력, 흡연여부등을조사하였다. 고혈압의정의는고혈압의과거력을가지고있거나, 현재항고혈압제를투여받고있거나, Seventh Joint National Committee Classification of Blood Pressure(JNC-VII) 기준으로수축기혈압이 140 mmhg 이상, 이완기혈압이 90 mmhg 이상으로정의하였다. 11) 당뇨병의정의는과거에당뇨병의진단을받았거나현재당뇨병으로치료중이거나, 치료를받지않은사람은 American Diabetes Association 기준상공복시혈당이 126 mg/dl 이상인경우로하였다. 12) 모든참여자들은 12시간이상공복상태를확인후채혈검사를시행하였다. 혈청총콜레스테롤농도와중성지방농도는 enzymatic calorimetric test 로측정하였고, 고밀도지단백콜레스테롤은 selective inhibition 방법으로, 저밀도지단백콜레스테롤은 homogeneous enzymatic calorimetric test 로측정하였다 (Hitachi 747, Hitachi, Japan). 아포지단백 B의농도와아포지단백 A 1 의농도는 rate nephelometry 방법을이용하여정량측정하였다 (IMMAGE system; Beckman Coulter, Fullerton, CA, USA). 혈압은 Hypertension Detection and Follow-up Program protocol에따라수검자가 5분이상안정한후표준화된수은혈압기를이용하여측정하였으며키, 체중은자동측정기를이용하였고, 체질량지수 (kg/m 2 ) 는측정된키와체중을이용하여구하였다. 13) 통계처리통계분석은 SPSS program for Window(version 11.0) 팩키지를이용하여시행하였다. 모든결과는평균 ± 표준편차표시하였으며여러변수사이의연관성을평가하기위해 Pearson s correlation coefficients 를이용하였다. 일치 / 불일치의평가는각각의변수를 5군 (quintile) 으로나누어두변수가같은군에있을경우를일치, 그렇지않은경우를불일치로정의하였다. 그리고두연관된변수의동의의정도 (degree of agreement) 를알아보기위해 k statistics 를이용하였다. 저밀도지단백콜레스테롤과아포지단백 B 사이의일치 / 불일치군간임상변수들과의비교분석을위해불일치군중저밀도지단백콜레스테롤이아포지단백 B 보다높은군을 group Ⅰ, 반대인경우를 group Ⅱ 그리고일치군을 group Ⅲ로정하였다. Group Ⅰ, Ⅱ, Ⅲ 사이의변수들의차이비교는 one-way ANOVA test 를이용하였고, 교차비는 χ 2 -test 를이용하여검정하였으며, 비교위험도는 multinomial logistic regression analysis 를이용하여분석하였다. P<0.05 를통계학적으로유의하다고판정하였다. 결과 전체연구대상자 11,816 명 ( 남자 6,965 명, 여자 4,851 명 ) 의평균연령은 45.9±11.3 세, 혈청총콜레스테롤농도 (TC) 는 207.7±37.0 mg/dl, 혈청중성지방농도 (TG) 는 151.3± 106.2 mg/dl, 혈청고밀도지단백콜레스테롤농도 (HDL- C) 는 56.4±14.7 mg/dl, 혈청저밀도지단백콜레스테롤농도 (LDL-C) 는 120.0±30.8 mg/dl, 비고밀도지단백콜레스테롤농도 (non-hdl-c) 는 151.3±38.2 mg/dl 이었다. 아포지단백 B(Apo-B) 의농도는 99.8±26.8 mg/dl, 아포지단백 A1(Apo-A 1) 의농도는 118.7±21.8 mg/dl, Apo B/ Apo A 1 는 0.9±0.3 이었다 (Table 1). 성별에따른인체계측학적 (anthropometrical), 생화학적변수들의평균의차이를분석한결과, 여자에서나이, 고밀도지단백콜레스테롤, 아포지단백 A 1 이통계학적으로유의하게높았고, Table 1에기술한나머지변수들은남자에서통계학적으로유의하게높았다. 아포지단백과다른콜레스테롤지표에영향을주는나이, 혈압, 체질량지수, 허리둘레, 공복혈당, 당뇨병, 흡연력등을보정한결과, TC, Apo-B, Apo-B/A 1 은남자에서높았고, HDL-C 은여자에서높았다. 콜레스테롤지표들과아포지단백사이의상관관계를분석한결과, LDL-C 과 Apo-B, non-hdl-c 과 Apo-B 사이에는각각 r=0.734, r=0.830 으로높은상관성을보였다 (Table 2). LDL-C 과 Apo-B 사이의일치 / 불일치를분석한결과, 전체일치도는 47.6% 였으며남자가 47.1%, 여자가 48.4% 였다. 또한일치는 1군과 5군에서중간군보다더높게나타났다 (>60%: 33~40%). non-hdl-c 과 Apo-B 사이의전체일치도는 56.2%, TC/HDL-C 과 Apo-B/A1 의비사이의전

438 Korean Circulation J 2005;35:436-442 Table 1. Characteristics of study population Total (n=11816) Men (n=6965) Women (n=4851) Age (years) 45.9±11.3 45.7±11.0 46.2±11.7 Systolic BP (mmhg) 120.3±18.00 120.8±16.10 119.6±20.40 Diastolic BP (mmhg) 76.8±11.7 78.1±11.2 74.9±12.2 Body mass index (kg/m 2 ) 23.8±3.10 24.2±2.80 23.2±3.30 Waist circumference (cm) 80.5±9.10 84.4±7.50 74.8±8.40 Total cholesterol (mg/dl) 207.7±37.00 209.0±36.40 205.9±37.80 Triglyceride (mg/dl) 151.3±106.2 167.9±115.5 127.6±85.90 HDL-C (mg/dl) 56.4±11.7 52.9±13.1 61.5±15.3 LDL-C (mg/dl) 120.0±30.80 121.5±30.40 117.9±31.20 Non-HDL-C (mg/dl) 151.3±38.20 156.1±37.00 144.4±38.80 TC/HDL-C 3.85±1.13 4.16±1.17 3.54±1.03 Apo A 1 (mg/l) 118.7±21.80 117.2±21.20 120.7±22.50 Apo B (mg/l) 99.8±26.8 103.9±26.00 93.9±26.7 Apo B/Apo A 1 0.87±0.29 0.92±0.29 0.81±0.29 Fasting glucose (mg/dl) 94.3±22.8 96.6±23.9 90.9±20.7 Hypertension (n (%)) 3193 (27%).0 2007 (28.8%) 1186 (24.4%) Smokers (n (%)) 1050 (08.9%) 0945 (13.6%) 0105 (02.2%) Diabetes mellitus (n (%)) 0696 (05.9%) 0466 (06.7%) 0230 (04.7%) Values are mean±sd. All p<0.001. HDL-C: high density lipoprotein-cholesterol, LDL-C: low density lipoprotein-cholesterol, TC: total cholesterol, Apo: apolipoprotein, BP: blood pressure Table 2. Correlation coefficients within lipoprotein parameters Total Men Women LDL-C and Apo B 0.734 0.723 0.756 Non-HDL-C and Apo B 0.830 0.814 0.841 Triglyceride and Apo B 0.331 0.279 0.372 Total cholesterol and Non-HDL-C 0.924 0.936 0.921 TC/HDL-C and Apo B/Apo A 1 0.726 0.695 0.749 All p<0.01. Apo: apolipoprotein, HDL-C: high density lipoprotein -cholesterol, LDL-C: low density lipoprotein-cholesterol, TC: total cholesterol 체일치도는 53.9% 였다. 그러나전체대상의 1/3 이상에서불일치를보였다 (Table 3). 콜레스테롤지표들과아포지단백사이의동의의정도 (degree of agreement) 를분석한결과, 경도 (fair) 및중등도 (moderate) 의동의의정도를보였고그중에서 non-hdl- C과 Apo-B 사이의일치의정도가가장높은결과 (k=0.45) 를보였다 (Table 4). LDL-C 과 Apo-B 사이의일치 / 불일치군을세 group 으로나누어각군간의변수의차이를분석한결과, 아포지단백 B가저밀도지단백콜레스테롤보다높은불일치군인 group II가다른군들에비해고령, 남자의빈도가많았으며, TG, non-hdl-c, Apo-B/A 1, 공복혈당, 혈압, 체질량지수, 허리둘레등이유의하게높았고고혈압, 당뇨병, 흡연의기왕력도높았다. 반면 TC, LDL-C 등은유의하게낮은소견을보였다 (Table 5). Apo-B 와 LDL-C 사이에불일치의증가를분석하기위해다변량명목회귀분석한결과 Apo-B 와 LDL-C 의일치 군에비하여 Apo-B 가 LDL-C 보다높은불일치군의비교위험도는남자, 고령, 흡연군에서증가하였고, 중성지방, 고밀도지단백콜레스테롤이높을수록, 총콜레스테롤이낮을수록, 허리둘레가클수록비교위험도가증가함을관찰할수있었다. 일치군에비해 LDL-C 이 Apo-B 보다높은불일치군의비교위험도는남자, 흡연, 당뇨군에서감소하였고총콜레스테롤이높을수록, 고밀도지단백콜레스테롤이낮을수록비교위험도가증가함을관찰할수있었다 (Table 6). 고찰 본연구에서혈중저밀도지단백콜레스테롤농도및여러콜레스테롤지표들과아포지단백사이의일치도와연관성을알아본결과, Apo-B 와 LDL-C 및여러콜레스테롤지표사이에높은연관성이있었으나이들간에낮은일치도를보였다. 특히고령, 남자, 흡연력이있는경우, 중성지방, 고밀도지단백콜레스테롤이높을수록, 총콜레스테롤이낮을수록, 허리둘레가클수록 Apo-B 가 LDL-C 보다높은불일치군의빈도가많음을알수있었다. LDL-C 농도는혈장 100 ml내에들어있는저밀도지단백입자 (LDL particles) 내의콜레스테롤의양을말하며지질대사이상의치료의주된지표이다. 1) 그러나 LDL-C 농도는 TG가높은사람에서는 LDL-C 입자의수와크기에서많은차이를보이며전체지단백입자의양을대변하지못하여최근 Apo-B 가총동맥경화능 (total atherogenic potential) 의지표로서사용되어지고있다. 14) 아포지단백은지단백의

Sang Tai Hwang, et al:concordance/discordance between Apo-B Level and Cholesterol Index 439 Table 3. Concordance analysis by quintiles among various atherogenic indexes Apo B and LDL cholesterol levels Quintiles of Apo B (mg/dl) Quintiles of LDL-C (mg/dl) <77 77-92 92-105 105-122 122< <94 62.7%* 21.1%* 08.8%* 5.4%* 2.0% *94-111 23.5%* 39.9%* 21.9%* 11.1%* 3.6% 111-126 08.1%* 26.3%* 33.3%* 24.3%* 8.0% 126-145 04.5%* 09.6%* 25.2%* 37.4%* 23.3% 145< 02.3%* 02.5%* 06.7%* 23.3%* 65.2%* Apo B and non-hdl cholesterol levels Quintiles of non-hdl-c (mg/dl) Quintiles of Apo B (mg/dl) <77 77-92 92-105 105-122 122< <119 71.0%* 24.5%* 03.1%* 00.2%* 00.3%* 119-139 17.1%* 47.1%* 29.6%* 05.8%* 00.4%* 139-159 05.8%* 20.3%* 40.2%* 30.4%* 03.3%* 159-182 04.0%* 05.4%* 18.8%* 48.0%* 23.7%* Apo B and triglyceride levels 182< 02.3%* 02.1%* 04.4%* 16.9%* 74.2%* Quintiles of triglyceride (mg/dl) Quintiles of Apo B (mg/dl) <77 77-92 92-105 105-122 122< <80 40.7%* 27.2%* 17.3%* 10.5%* 04.3%* *80-108 21.4%* 24.8%* 23.0%* 19.8%* 11.0%* 108-143 15.1%* 20.5%* 21.5%* 24.1%* 18.9%* 143-203 08.9%* 14.6%* 20.7%* 26.2%* 29.6%* >203 07.8%* 11.7%* 15.6%* 24.5%* 40.4%* Total cholesterol/hdl cholesterol and Apo B/Apo A 1 Quintiles of TC/ HDL-C Quintiles of Apo B/Apo A 1 <0.63 0.63-0.77 0.77-0.91 0.91-1.08 1.08< <2.91 71.0%* 23.1%* 03.7%* 01.3%* 01.0%* 2.91-3.49 19.8% 46.8%* 25.9%* 05.8%* 01.8%* 3.49-4.07 04.1% 21.9%* 42.8%* 26.0%* 05.2%* 4.07-4.78 03.0% 05.5%* 21.1%* 43.5%* 26.9%* 4.78< 01.9% 02.9%* 06.6%* 23.4%* 65.2%* *: concordant LDL cholesterol and Apo B data (i.e., the proportion of population in whom both atherogenic indexes fell into the same quintile of the distribution). Apo: apolipoprotein, LDL-C: low density lipoprotein-cholesterol, non-hdl-c: non-high density lipoproteincholesterol, HDL-C: high density lipoprotein-cholesterol, TC: total cholesterol 구조적안정성과대사방향을결정하는것으로알려져있으며, 이들중 Apo-B 는 VLDL, IDL, LDL 입자각각에하나씩포함되어혈중동맥경화성입자의총수와일치한다. 15) Sniderman 등 16) 은제 2 형당뇨병환자에서고중성지방혈증과고아포지단백 B 혈증이있는경우에심혈관질환의발생이가장높으며그이유로고밀도소립 LDL 의입자수가증가하기때문으로설명하고, Apo-B 측정이 LDL-C 보다심혈관질환의발생을예측하는데더정확하다고하였다. 혈청비고밀도지단백콜레스테롤은총콜레스테롤에서고밀도지단백콜레스테롤을뺀값으로 VLDL, IDL, LDL 콜레스테롤의합을의미하며 2형당뇨병환자에서 LDL-C 을대신하여고지혈증의치료지표로사용되며최근에는심혈관질환과이로인한사망의좋은예측인자로알려져있다. 17-19) 또한 NCEP-ATP Ⅲ에서도중성지방이높은 (200 mg/dl<triglyceride<500 mg/dl) 환자에서는유용성 (availability), 경제성 (cost) 을고려하여 Apo-B 와강한연관성이있는 non-hdl-c 을 Apo-B 측정을대체하여콜레스테롤을낮추는치료의이차적지표로서그기준을제시하였다. 1) 본연구에서도 Apo-B 는 LDL-C(r=0.734), non-hdl-c (r=0.83) 등과높은연관성이있었다. 이는이전의연구들에서보고한것과유사하다. 20-22) 그러나 Sniderman 등 22) 은 Quebec cardiovascular study 에참여한 2,103 명의남자를대상으로 Apo-B 와여러콜레스테롤지표사이에일치도를조사한결과, Apo-B 는 non- HDL-C 과강한연관성이있으나 (r=0.87) 단지중등도의동의 (agreement(k=0.47)) 를보여여러콜레스테롤지표들과 Apo-B 는상호보완적관계로, 심혈관질환의위험을평가하는데콜레스테롤지표들의측정과함께 Apo-B 측정이필요

440 Korean Circulation J 2005;35:436-442 Table 4. Degree of agreement among various atherogenic indexes Total Atherogenic indexes k* Agreement Apo B vs TC 0.34 Fair Apo B vs LDL-C 0.35 Fair Apo B vs non-hdl-c 0.45 Moderate Apo B vs triglyceride 0.15 Slight Apo A1 vs HDL-C 0.28 Fair TC/HDL-C vs Apo B/Apo A1 0.42 Moderate Men Atherogenic indexes k* Agreement Apo B vs TC 0.35 Fair Apo B vs LDL-C 0.35 Fair Apo B vs non-hdl-c 0.43 Moderate Apo B vs triglyceride 0.12 Slight Apo A1 vs HDL-C 0.30 Fair TC/HDL-C vs Apo B/Apo A1 0.40 Fair Women Atherogenic indexes k* Agreement Apo B vs TC 0.35 Fair Apo B vs LDL-C 0.39 Fair Apo B vs non-hdl-c 0.46 Moderate Apo B vs triglyceride 0.17 Slight Apo A1 vs HDL-C 0.27 Fair TC/HDL-C vs Apo B/Apo A1 0.43 Moderate *: the k statistics, on a scale from 0 to 1, reflects the degree of agreement between 2 variables, : the levels of agreement range from slight (k 0.0 to 0.20), fair (0.21 to 0.40), moderate (0.41 to 0.60), substantial (0.61 to 0.80), and to almost perfect (0.81 to 1.00), according to Landis and Koch. 25) Apo: apolipoprotein, HDL-C: high density lipoprotein-cholesterol, LDL-C: low density lipoproteincholesterol, TC: total cholesterol Table 6. Multinomial logistic regression analyses with concordance, moderately discordant LDL-C and Apo B levels as dependent variables Group III vs Group II Variable Odds 95% CI p Sex (men) 1.368 (1.214-1.542) <0.001 Age 1.021 (1.016-1.026) <0.001 Total cholesterol 0.960 (0.956-0.964) <0.001 HDL-cholesterol 1.029 (1.025-1.034) <0.001 Triglyceride 1.003 (1.002-1.004) <0.001 Waist circumference 1.023 (1.015-1.030) <0.001 Smoking 2.146 (1.835-2.509) <0.001 Hypertension 1.113 (0.990-1.251) <0.074 Diabetes mellitus 0.907 (0.734-1.121) <0.366 Group III vs Group I Variable Odds 95% CI p Sex (men) 0.876 (0.774-0.992) <0.037 Age 1.002 (0.997-1.008) <0.358 Total cholesterol 1.017 (1.012-1.021) <0.001 HDL-cholesterol 0.984 (0.979-0.988) <0.001 Triglyceride 0.999 (0.999-1.000) <0.108 waist circumference 1.002 (0.994-1.009) <0.695 Smoking 0.563 (0.445-0.712) <0.001 Hypertension 0.912 (0.806-1.033) <0.148 Diabetes mellitus 0.734 (0.584-0.922) <0.008 Group I refers to subjects belong to an LDL-cholesterol quintile that was higher than its corresponding Apo B quintile, Group II refers to subjects belong to an Apo B quintile that was higher than its corresponding LDL cholesterol quintile, Group III refers to subjects with concordance of Apo B and LDL cholesterol Table 5. Characteristics of Individuals with concordance, moderately discordant LDL-C and Apo B levels Group I (n=3137) Group II (n=3055) Group III (n=5624) Men n (%) 1483 (47.3%) 2204 (72.1%) 3278 (58.3%) Age (years) 44.7±11.4 48.1±10.8* 045.4±11.4* Systolic BP (mmhg) 118.7±17.60 123.2±17.7*0 119.7±18.2* Diastolic BP (mmhg) 75.5±11.4 78.9±11.6* 076.3±11.8* Body mass index (kg/m 2 ) 23.3±3.00 24.5±2.8*0 023.6±3.1* Waist circumference (cm) 78.3±8.90 83.8±8.0*0 079.9±9.3* Total cholesterol (mg/dl) 212.4±27.70 203.8±30.1*0 207.3±44.0* Triglyceride (mg/dl) 114.3±68.00 222.0±144.7* 133.6±77.3* HDL-C (mg/dl) 61.7±14.8 49.2±12.1* 057.4±14.4* LDL-C (mg/dl) 129.4±21.40 107.3±20.3*0 121.8±37.1* Non-HDL-C (mg/dl) 150.7±28.40 154.5±30.9*0 149.9±45.6 * TC/HDL-C 3.62±0.98 4.35±1.13* 03.82±1.20* Apo A 1 (mg/l) 116.3±23.90 118.1±20.3*0 120.3±21.2* Apo B (mg/l) 88.4±17.9 109.8±18.7*0 100.8±31.8* Apo B/Apo A 1 0.80±0.25 0.96±0.25* 00.87±0.32* Fasting glucose (mg/dl) 90.9±17.8 99.1±27.8* 093.5±21.8* Hypertension n (%) 707 (22.5%) 1043 (34.1%) 1443 (25.7%) Smokers n (%) 0146 (04.7%) 0406 (13.3%) 0498 (08.9%) Diabetes mellitus n (%) 0110 (03.5%) 0277 (09.1%) 0309 (05.5%) Values are mean±sd. All p<0.001. Group I refers to subjects belong to an LDL-cholesterol quintile that was higher than its corresponding Apo B quintile, Group II refers to subjects belong to an Apo B quintile that was higher than its corresponding LDL cholesterol quintile, Group III refers to subjects with concordance of Apo B and LDL cholesterol, HDL-C: high density lipoprotein-cholesterol, LDL-C: low density lipoproteincholesterol, Apo: apolipoprotein, BP: blood pressure, TC: total cholesterol. *: significantly different for Group I vs. Group II or III, : significantly different Group II vs. Group III by Student-Newman-Keuls post hoc analysis, p<0.05. : chi-square for linear trend: p<0.001

Sang Tai Hwang, et al:concordance/discordance between Apo-B Level and Cholesterol Index 441 할수있다는것을주장하였다. 이는본연구에서도유사한결과를보였다 (r=0.83, k=0.45). 이러한차이는상관분석이두변수간에직선적인연관성의정도를나타낼뿐, 어떤경우에서는연관의분산값 (dispersion of values) 으로서정보를제공하지않기때문에전반적인연관성의정확한측정이아니라는통계적사실에기초한다. Wagner 등 23) 은제 2형당뇨병이있는환자에서이상고지혈증의고위험군을진단함에있어고중성지방혈증이있는경우 Apo-B 와 non-hdl-c 이동등한결과를보였지만정상중성지방혈증에서는 Apo-B 가더유용한결과를얻었다고보고하였다. 또한 Apo-B 가경동맥내막 -중막두께와심혈관질환을예측하는데 non-hdl-c 보다우월하다고하였다. 3) 이것또한 Apo-B 와 non-hdl-c 이심혈관질환을예측하는데서로동등하지않으며대체가능하지않음을시사한다. Walldius 등 7) 은심혈관질환의위험을예측하는데있어서 LDL-C 이남자에서는유용하지만여자및노인에서는그렇지않으며, Apo-B 와 Apo-A1 이성별이나나이, 중성지방의농도와상관없이심혈관질환의위험을예측하는데 LDL-C 보다유용하다고하였다. 본연구의결과를고려해볼때현재콜레스테롤강하요법의기준으로널리사용중인 NCEP ATP III 지침에근거하여실제임상에서적용할경우, Apo-B 가 LDL-C 보다높은불일치를보일위험이있는고령, 흡연군, 남자에서, 그리고총콜레스테롤이낮거나중성지방, 고밀도콜레스테롤이높거나허리둘레가큰경우약물치료등의적극적인콜레스테롤강하요법의대상에서제외될수있음을시사한다. 특히흡연군과남자에서 Apo-B 가 LDL-C 보다높은불일치를보일위험이각각 2.1 배, 1.4 배높은결과를보였다. 과거문헌들에의하면흡연은트리아실글리세롤 (triacylglycerol) 의합성과대사에영향을주어트리아실글리세롤의혈중농도를증가시키며, 25)26) LDL 의입자크기는혈중트리아실글리세롤의농도와밀접한연관성을가지다고보고한바있다. 27)28) 또한 Griffin 등 28) 은흡연군에서비흡연군보다 LDL- III 에대한 LDL-I 의비가낮은결과를보였지만이를트리아실글리세롤로보정한후두군간의차이는상쇄되었다고보고하였다. 본연구에서는트리아실글리세롤을보정한후에도흡연군에서 apo-b 가 LDL-C 보다높은불일치를보일위험이높게측정되었다. 이에대한설명은 LDL subfraction 을함께측정하지않아제한점이있다. 성별은고밀도소립 LDL 에영향을주는인자로보고되고있다. 29)30) Nikkila 등 30) 은여성에서남성보다 LDL 입자가크고저동맥경화성 (less atherogenic) 을보인다고보고하였고, 이는여성호르몬에의한간지질분해효소 (hepatic lipase) 의활성저하에기인한다고제시해왔다. 본논문의결과에서 Apo-B 가 LDL-C 보다높은불일치군이남자에서많은것은남자에서고밀도소립 LDL 이여자에비해많음에기 인한것으로추측된다. 본연구는단면적연구이기때문에 Apo-B 와 LDL-C 이일치하는군과일치하지않는군사이에실제심혈관질환의유병률이나콜레스테롤강하요법의효과의차이를알수없었다는점, 경구당부하검사등의당뇨병에대한정확한검사를시행하지못했다는점, 건강검진수진자라는대상자의특성으로인해선택편견이있을수있다는점등의제한점이있다. 하지만많은수의대상인구를통하여 Apo-B 와다른여러콜레스테롤지표들사이의연관성과일치도를조사하였다는데의의가있다고생각한다. 결론적으로본연구에서는 Apo-B 와 LDL-C 및여러콜레스테롤지표사이에높은연관성이있었으나이들간에낮은일치도를보였다. 특히고령, 흡연군, 그리고남자에서, 또한총콜레스테롤이낮은경우, 중성지방, 고밀도콜레스테롤이높은경우, 허리둘레가클수록 Apo-B 가 LDL-C 보다높은불일치의비교위험도가일치를보인군보다증가한본논문의결과를고려해볼때, 실제임상에서널리이용되고있는표준지질검사와함께총동맥경화능의지표로사용되고있는 Apo-B 의측정을추가함으로써심혈관질환의위험인자의평가및콜레스테롤의강화요법의치료에도움이될수있을것으로사료된다. 하지만향후심혈관질환의위험인자로서 Apo-B 농도및 LDL-C 농도를기준으로한심혈관질환의유병률이나치료의효과에대한전향적인연구가필요할것으로생각된다. 요약 배경및목적 : 혈중아포지단백 B는혈중총콜레스테롤, 저밀도지단백콜레스테롤, 비고밀도지단백콜레스테롤보다관동맥질환의위험을예측하는데보다효과적이라는연구들이보고되고있다. 본연구는콜레스테롤지표들과아포지단백사이의일치도를알아보고이에영향을주는인자들에대해평가하고자하였다. 방법 : 2002 년 1월부터 12월까지강북삼성병원에서종합건강검진을받은관동맥질환의기왕력이없는수진자 11,816 명을대상으로하였다. 문진, 진찰및생화학적검사들을통해아포지단백과콜레스테롤지표들사이의일치도와일치 / 불일치에영향을주는심혈관질환의위험요소를알아보았다. 결과 : 아포지단백 B와여러콜레스테롤지표사이에강한연관성을보였으나일치도는 47~56% 에서보였다. 다변량명목회귀분석결과, 고령, 흡연군, 남자, 중성지방, 고밀도지단백콜레스테롤이높을수록, 총콜레스테롤이낮을수록, 허리둘레가클수록아포지단백 B가저밀도지단백콜레스테롤보다높은불일치가증가함을알수있었다.

442 Korean Circulation J 2005;35:436-442 결론 : 고령, 흡연군, 그리고남자에서, 또한총콜레스테롤이낮을수록, 중성지방, 고밀도콜레스테롤이높을수록, 허리둘레가클수록 Apo-B 가 LDL-C 보다높은불일치군의위험이증가한다. 따라서표준지질검사와함께 Apo-B 의측정을추가함으로써심혈관질환의위험인자의평가및콜레스테롤의강화요법의치료에도움이될수있을것으로사료된다. 중심단어 : 아포지단백 B; 저밀도지단백콜레스테롤. REFERENCES 1) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97. 2) Grundy SM. Cholesterol-lowering clinical trials: a historical perspective. In: Grundy SM, editor. Cholesterol Lowering Therapy: evaluation of clinical trial evidence. New York, NY: Marcel Dekker, Inc; 2000. p.1-44. 3) Sniderman AD, Furberg CD, Keech A, et al. Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment. 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