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1 대한내과학회지 : 제 78 권제 2 호 2010 원저 전당뇨병환자에서 ApoB/ApoA-I Ratio와비알코올성지방간과의연관성 성균관대학교의과대학강북삼성병원 1 내과, 2 영상의학과 이지애 1 장승훈 1 민재훈 1 김태완 1 정우신 1 심충남 1 허운제 1 정미연 1 이현아 1 조용균 1 홍현표 2 The relationship between the ApoB/ApoA-I ratio and non-alcoholic fatty liver disease in prediabetic patients Ji Ae Lee, M.D. 1, Seung Hun Jang, M.D. 1, Jae Hoon Min, M.D. 1, Tae Wan Kim, M.D. 1, Woo Shin Jeong, M.D. 1, Choong Nam Shim, M.D. 1, Woon Je Heo, M.D. 1, Mi Youn Jung, M.D. 1, Hyon A Lee, M.D. 1, Yong Kyun Cho, M.D. 1, and Hyun Pyo Hong, M.D. 2 Departments of 1 Internal Medicine and 2 Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea Background/Aims: The apolipoprotein B/A-I ratio (ApoB/A-I) is a powerful clinical indicator of atherosclerosis. Although numerous reports have shown the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular disease, few reports have examined the relationship between NAFLD and the ApoB/A-I ratio. The aim of the study was to determine the association between NAFLD and the ApoB/A-I ratio in prediabetic patients. Methods: This cross-sectional study was performed with data obtained from 701 patients (mean age, 47.9±9.6 years) diagnosed with prediabetes. Serum lipid profiles including lipoprotein, apolipoprotein, and calculated ApoB/A-I ratio as well as metabolic syndrome parameters such as fasting glucose and insulin were measured in each subject. Results: Among the 701 patients, 340 (48%) had NAFLD. The number of male patients was 490 (NAFLD+, 276; and NAFLD-, 214). The odds ratios for the prevalence of NAFLD increased according to the quartiles of the ApoB/A-I ratio (1.886, 2.245, and 2.587) (p<0.001). Conclusions: The prevalence of NAFLD correlated with high ApoB/A-I ratio, suggesting that NAFLD increases the risk for atherosclerosis progression in male prediabetic patients. (Korean J Med 78: , 2010) Key Words: NAFLD; Apolipoprotein B; Apolipoprotein A-I; Prediabetes; Atherosclerosis Received: Accepted: Correspondence to Yong Kyun Cho, M.D., Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul , Korea choyk2004.cho@samsung.com

2 - The Korean Journal of Medicine: Vol. 78, No. 2, 서 론 2. 연구방법 공복혈당장애및내당능장애를포함하는전당뇨병은당뇨병의전단계로인정되고있으며인슐린저항성증가와함께다양한지방대사이상및죽상경화와관련되어전당뇨병단계에서이미심혈관계질환의위험성이증가하는것으로알려져있다 1,2). 혈중콜레스테롤이이러한심혈관계질환발생의예측인자로사용되어져왔으나최근에는혈중아포지질단백 (Apolipoprotein) 에대한관심이커지고있다. 아포지질단백 A-I (ApoA-I) 은고밀도지질단백의가장큰구성요소이고아포지질단백 B-100 (ApoB) 는 chylomicron에존재하며중성지방이풍부한초저밀도지질단백과저밀도지질단백의체내양을반영한다 3,4). 따라서 ApoB 와 ApoA-I 의비율 (ApoB/ A-I ratio) 이인슐린저항과지방대사이상을평가하는지표일수있으며심혈관계질환의발생을예측하는데있어콜레스테롤보다도유용하다는연구가있다 5-7). 비알코올성지방간 (non-alcoholic fatty liver disease, NAFLD) 은인슐린저항성을근간으로하는대사증후군의간내발현으로생각되고있으며성인인구의 15~25% 정도를차지하는흔한간질환으로우리나라의경우도그수가꾸준히증가하고있다. 단순지방간 (simple steatosis) 에서부터비알코올성지방간염 (non-alcoholic steatohepatitis, NASH), 간경변증, 간세포암같은다양한범주를포함하며 8), 대사증후군이심혈관계질환의위험성을증가시키듯 NAFLD 의존재가심혈관계질환의위험인자라는연구결과가보고되고있다 9). 그러나아직 NAFLD 와 ApoB/A-I ratio 의관계에대한연구는드문상태이며, 본연구에서는전당뇨병환자에서 NAFLD 의임상적의미를파악하고 ApoB/A-I ratio와의연관성을확인하려하였다. 대상및방법 1. 연구대상 2006년부터 2007년까지강북삼성병원건강검진에서전당뇨병으로새롭게진단되어검사참여에동의한 701명을대상으로하였다. 바이러스성간염의병력, 주당 30 g 이상의음주력, 지방간을일으킬수있는약물복용력, 당뇨병이나심혈관계질환의병력이있는경우는제외하였다. 연구약정서는본원임상시험연구위원회의승인을받았으며 1975년헬싱키선언의윤리기준을준수하였다. 1) 신체계측체중, 신장, 체질량지수, 허리둘레, 엉덩이둘레, 수축기및이완기혈압을측정하였다. 체질량지수는체중을신장의제곱으로나누어계산 (kg/m 2 ) 하여구하였다. 허리둘레와엉덩이둘레는직립자세에서배꼽부위와대퇴골대전자부위의둘레를측정하였다. 혈압은최소 10분이상안정한후수은주혈압계를이용하여숙련된간호사가 2회측정하여평균값을기록하였다. 2) 혈액검사 12시간이상의금식후에정맥에서채혈하여간기능검사, 혈중지질검사및혈당검사와혈청검사를시행하였다. 각종생화학적검사는 Bayer Reagent Packs on an automated chemistry analyzer (ADVIA 1650 Autoanalyzer; Bayer Health- Care, Tarrytown, NY) 를이용하여측정했다. 공복혈당은헥소키나아제법으로측정하였고, 총콜레스테롤, 고밀도지질단백, 저밀도지질단백, 중성지방은효소비색법 (enzymatic colorimetric assay) 을사용하였다. 인슐린은 BioSource INS-IRMA kit (BioSource, Belgium) 를사용하여방사면역계수측정법 (immunoradiometric assay) 으로측정하였다. ApoA-I과 ApoB 측정은 Boehringer Mannheim procedure를이용하여면역비탁법으로하였다. 인슐린저항성의지표로 homeostasis model of assessment (HOMA-IR) 을사용하였고, 계산은다음식을이용하였다 10). HOMA-IR= 공복인슐린 (μu/ml)x 공복혈당 (mmol/l)/22.5 3) NAFLD 의진단연구의특성상비침습영상검사인복부초음파 (ASPEN; Acuson, Pennsylvania, USA) 를시행하여간지방증을평가하였다. 3.5 MHz 의탐촉자로 1인의방사선과전문의에의하여시행되었으며간지방증의진단은미만성의고에코결 (a diffuse hyperechoic echotexture), 우측신장의피질에비교한간반향의증가및혈관의불명료성 (vascular blurring), 심부반향의감쇠 (deep-echo attenuation) 의소견들을고려하였으며간기능검사의이상유무와관계없이 NAFLD 로진단하였다. 4) 전당뇨병의평가이전에특별한병력이없었으나공복혈당이 100 mg/dl 이상높게관찰되거나당뇨병이의심되는환자에서 75그램

3 - Ji Ae Lee, et al. ApoB/ApoA-I ratio and non-alcoholic fatty liver disease - 경구당부하검사 (oral glucose tolerance test, OGTT) 를시행하였다. 공복혈당장애는공복혈장혈당 100~125 mg/dl, 내당능장애는경구당부하 2시간후혈장혈당 140~199 mg/dl를진단기준으로하였다. 3. 통계분석연속변수는평균및표준편차로, 범주형변수는빈도수와 % 로표시하였다. 통계분석은 Statistical Package for Social Science 11 (SPSS; Chicago, IL, USA) 프로그램을이용하였다. 단변량분석시연속변수의비교에는 student t-test를이용하였다. NAFLD 의유무에따른변수들의선형적증가를 4분위수로나누어 linear-by-linear association test로분석하였다. 다형회귀분석으로 Odds ratios 와 95% 신뢰구간을얻었다. 결과 1. 대상군의임상적특성전체연구대상인전당뇨병환자 701명중남자는 490명, 여자는 211명이었으며평균연령은 47.9±9.6세였다. 대상자가운데공복혈당장애만있는경우가 377명 (53.8%), 내당능장애만나타난경우가 26명 (3.7%), 공복혈당장애 + 내당능장애모두를보인경우가 298명 (42.5%) 이었다. 전당뇨병환자중 NALFD 군은 340명 (48%) 이었다. 모든대상군의임상적특징은표 1에기술하였다. NAFLD 군의평균연령은 46.0세이고, 대조군의평균연령은 47.0세였다. 남자의비율이 NAFLD 군에서 81.2% 로대조군 59.3% 보다많았다 (p<0.001, 표 2). 연속변수중 NAFLD 군과대조군간에유의한차이를보인인구학적, 생화학적인자들은수축기및이완기혈압, 체질량지수, 허리둘레, AST (aspartate aminotransferase), ALT (alanine aminotransferase), 공복인슐린, 공복혈당, HOMA-IR, 총콜레스테롤, 고밀도지질단백, 저밀도지질단백, 중성지방, lipoprotein (a), ApoA-I, ApoB, ApoB/A-I ratio이었다 ( 표 2). 2. NAFLD와 ApoB/A-I ratio NAFLD군과대조군에서 ApoB/A-I ratio를 4분위수로나누어다형회귀분석을했다. 남성의경우다형회귀분석으로대사증후군의여러인자인나이, 체질량지수, 허리둘레, HOMA-IR 등을보정하여다변량분석을시행한결과 ApoB/ A-I ratio에따라 NAFLD 의발생이증가함을알수있었다 (OR= % CI=1.007~3.534 and 2.245, 1.215~4.148, and 2.587, 1.389~4.819, 표 3). 여성의경우동일한분석을시행하였을때 NAFLD 와 ApoB/A-I ratio 유의한상관관계가없었다 ( 표 4). 고 NAFLD 는음주경력이없는환자에서알코올성지방간과유사한조직소견을보이는질환이다. NAFLD 는단순지방간에서비알코올성지방간염, 진행된섬유화를가진비알코올성지방간염, 간경변증이포함된다. 비알코올성지방간염은 1980년병리학자인 Ludwig 등이처음보고하였고 11), 간의지방변성, 염증세포침윤, 간세포괴사, 섬유화의조직소견을보인다. NAFLD 는비만, 고지혈증, 인슐린저항성등이포함된대사증후군과연관되어있으며 12), NAFLD 가대사증후군의간내발현이라는점에서 13) 최근 NAFLD 가심혈관계질환에미치는역할에대해관심이높아지고있다. NAFLD 와 Table 1. Patient clinical characteristics (N=701) Mean±SD Age (years) 47.9±9.6 Gender, men (%) 490 (69.9) Height (cm) 166.8±7.9 Weight (kg) 69.0±10.5 BMI (kg/m 2 ) 24.7±2.7 Waist circumference (cm) 83.1±7.9 Systolic BP (mmhg) 119.9±16.1 Diastolic BP (mmhg) 77.3±9.3 AST (IU/L) 25.6±13.0 ALT (IU/L) 28.1±19.4 Insulin (uiu/ml) 10.7±3.7 Glucose (mg/dl) 107.4±7.2 HOMA-IR 2.8±1.0 Total cholesterol (mg/dl) 202.9±35.6 HDL-cholesterol (mg/dl) 48.1±10.7 LDL-cholesterol (mg/dl) 119.6±31.1 Triglyceride (mg/dl) 169.0±126.3 ApoA1 (mg/dl) 137.9±20.6 ApoB (mg/dl) 104.6±22.2 Data are expressed as the means±sds or n (%). BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HOMA-IR, homeostasis model assessment-insulin resistance. 찰

4 - 대한내과학회지 : 제 78 권제 2 호통권제 594 호 Table 2. Baseline characteristics of patients with prediabetes according to the presence of NAFLD Negative n=361 NAFLD Positive n=340 p value Age (years) 47.0 (42.5~55.0) 46.0 (40.0~53.0) Male (n, %) 214 (59.3) 276 (81.2) <0.001 Weight (kg) 65.1± ±10.2 <0.001 BMI (kg/m 2 ) 23.5± ±2.5 <0.001 Waist circumference (cm) 79.7± ±6.6 <0.001 Systolic BP (mmhg) (104.0~128.0) (110.0~132.0) <0.001 Diastolic BP (mmhg) 76.0 (70.0~80.0) 80.0 (72.0~86.0) <0.001 AST (IU/L) 22.0 (19.0~26.0) 25.0 (21.0~31.0) <0.001 ALT (IU/L) 19.0 (15.0~25.0) 30.0 (21.2~42.0) <0.001 Insulin (uiu/ml) 8.3 (6.8~10.0) 9.9 (8.1~12.3) <0.001 Glucose (mg/dl) (102.0~110.0) (103.0~122.0) HOMA-IR 2.3 (1.9~2.8) 2.9 (2.4~3.6) <0.001 Total cholesterol (mg/dl) (176.5~218.0) (184.3~227.0) <0.001 HDL-cholesterol (mg/dl) 49.0 (42.0~57.0) 43.0 (38.0~52.0) <0.001 LDL-cholesterol (mg/dl) 116.1± ± Triglyceride (mg/dl) (86.5~156.0) (122.0~236.0) <0.001 Lp(a) (mg/dl) 17.6 (10.0~29.7) 12.6 (8.7~25.8) <0.001 ApoA1 (mg/dl) (125.6~151.5) (122.8~146.3).002 ApoB (mg/dl) 99.8± ±21.8 <0.001 ApoB/A1 ratio 0.7± ±0.2 <0.001 Data are expressed as the means±sds or the number of patients and proportion (%) or median (interquartile range). NAFLD, non-alcoholic fatty liver disease; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HOMA-IR, homeostasis model assessment-insulin resistance; Lp(a), lipoprotein (a). 심혈관계질환의연관성연구를보면, 당뇨병환자에서 NAFLD 환자군이대조군에비해관상동맥질환, 뇌혈관질환, 말초혈관질환이증가하고 14), 또한일반성인을대상으로한연구에서도비만이나다른대사증후군의인자와는독립적으로 NAFLD 가있는환자에서심혈관계질환이더많이발생하였다 15,16). 전당뇨병환자를대상으로한본연구에서 NAFLD 가동반된군에서수축기및이완기혈압, 체질량지수, 허리둘레, AST, ALT, 공복인슐린, 공복혈당, HOMA-IR, 총콜레스테롤, 고밀도지질단백, 저밀도지질단백, 중성지방, lipoprotein (a), ApoA-I, ApoB, ApoB/A-I ratio가 NAFLD가없었던대조군에비해의미있는차이를보였다. 이것은 NAFLD 가비만, 고혈압, 고인슐린혈증, 고중성지방혈증과관련이있다는다른연구들과일치하는내용이며 17,18), NAFLD 가전당뇨병환자에서도심혈관계질환의위험인자일수있음을 시사하였다. NAFLD 가심혈관계질환의위험인자로작용하는기전은아직명확하게밝혀지지않았으나몇가지가설이제시되고있다. 첫째, NAFLD 가인슐린저항성과이상지질혈증을증가시켜죽상경화를악화시킨다 19). 둘째, 활성산소 (reactive oxygen) 에의한간세포손상과사이토카인방출및만성적, 잠재적인염증의결과로죽상경화가진행된다 20-22). 셋째, 아디포넥틴 (adiponectin) 과같은항동맥경화사이토카인의감소 23), 마지막으로식후지질단백대사의장애가죽상경화진행의원인일수있다 24,25). 최근 ApoB/A-I ratio는대사증후군및심혈관계질환의주요임상지표로발표되고있고, ApoB/A-I ratio가기존의지질검사 (lipid profile) 보다심혈관계질환을예측할수있는좋은지표라는연구결과가있다 26). ApoA-I은고밀도지질단백의가장큰구성요소이며 ApoB는 chylomicron에존재하며중

5 - 이지애외 10 인. ApoB/ApoA-I ratio 와비알코올성지방간 - Table 3. Association between the presence of NAFLD and ApoB/A1 ratio in men with prediabetes NAFLD Negative (n, %) Positive (n, %) ORs (95% CIs) ApoB/A1 ratio 1 st quartile 65 (63.1) 38 (36.9) 1 2 nd quartile 52 (43.0) 69 (57.0) (1.007~3.534) 3 rd quartile 51 (38.1) 83 (61.9) (1.215~4.148) 4 th quartile 46 (34.8) 86 (65.2) (1.389~4.819) Age (0.929~0.980) BMI (1.023~1.412) Waist circumference (1.029~1.161) HOMA-IR (1.158~1.925) Data are expressed as number of patients and proportion (%). Calculated using a logistic regression analysis. Adjusted for age, BMI, waist circumference, HOMA-IR 1 st quartile (<0.64), 2 nd quartile (0.65~0.76), 3 rd quartile (0.77~0.89), 4 th quartile (>0.90) NAFLD, non-alcoholic fatty liver disease; ORs, Odds ratios; CI, confidence interval; BMI, body mass index; HOMA-IR, homeostasis model assessment-insulin resistance. Table 4. Association between the presence of NAFLD and ApoB/A1 ratio in women with prediabetes NAFLD Negative (n, %) Positive (n, %) ORs (95% CIs) ApoB/A1 ratio 1 st quartile 62 (86.1) 10 (13.9) 1 2 nd quartile 38 (69.1) 17 (30.9) (0.743~5.253) 3 rd quartile 26 (65.0) 14 (35.0) (0.870~6.641) 4 th quartile 21 (47.7) 23 (52.3) (1.794~12.567) Age (0.968~1.040) BMI (0.897~1.425) Waist circumference (0.975~1.190) HOMA-IR (1.118~2.456) Data are expressed as number of patients and proportion (%). Calculated using a logistic regression analysis. Adjusted for age, BMI, waist circumference, HOMA-IR 1 st quartile (<0.64), 2 nd quartile (0.65~0.76), 3 rd quartile (0.77~0.89), 4 th quartile (>0.90) NAFLD, non-alcoholic fatty liver disease; ORs, odds ratios; CI, confidence interval; BMI, body mass index; HOMA-IR, homeostasis model assessment-insulin resistance. 성지방이풍부한초저밀도지질단백과저밀도지질단백의체내양을반영한다. 간으로의비에스테르화지방산 (nonesterified fatty acid) 유입이증가하는경우간에서의 ApoB 분비가증가되고이화작용 (catabolism) 에장애가생겨 ApoB의상승을일으킨다. 본연구에서전당뇨병남성환자의경우, 나이및대사증후군의여러인자인체질량지수, 허리둘레, HOMA-IR 등을보정한후에도 ApoB/A-I ratio 상승과 NAFLD 발생이유의한 상관관계가있었다. 따라서전당뇨병남성환자에서 ApoB/ A-I의측정은심혈관계질환의지표일뿐아니라 NAFLD 의발생을예측하는지표로도사용될수있을것이다. 대사증후군의유무가 ApoB/ApoA-I ratio 0.90을기준으로나뉜다는연구결과 27) 가있으며, ApoB/ApoA-I ratio 가남성에서 0.90, 여성에서 0.80 이상일경우심근경색의고위험군이라는보고도있었다 28,29). 따라서 NAFLD 발생에대한 ApoB/A-I ratio 의확정범위값 (cuf-off value) 에대한연구도필요할것이다

6 - The Korean Journal of Medicine: Vol. 78, No. 2, 그러나여성의경우 ApoB/A-I ratio와 NAFLD 발생과의상관관계가관찰되지않았다. 이것은지방의간내축적에있어에스트로겐의긍정적효과 (favorable effect) 에의한것으로생각되는데추후연구시에여성환자를폐경의유무에따라하위그룹분석 (subgroup analysis) 할필요성이있어보인다 30). 본연구의제한점은첫째, NAFLD 가초음파소견으로진단되었다는것이다. 지방간진단의가장정확한방법은조직학적소견이며간초음파는간내지방침착이적을때에는민감도가떨어지는단점이있고, 관찰자간변이가있어정확한진단에는한계가있다 31,32). 그러나초음파가비침습적이고안전하여많은집단의지방간유병률연구에이용되고있다. 둘째, 본연구는단면연구로진행되어전당뇨병이있는 NAFLD 남성환자에서 ApoB/A-I ratio의유의한증가는확인할수있었지만 NAFLD 의유무에따라심혈관계질환의발병률이달라짐은확인할수없었다. 향후전향적연구를통해 NAFLD 와 ApoB/A-I ratio 의관련성뿐아니라심혈관계질환의발병률까지규명할수있도록해야할것이다. 또한향후 NAFLD 발생에대한 ApoB/A-I ratio 의확정범위값에대한연구도필요할것이다. 요약목적 : 전당뇨병은인슐린저항성증가와함께다양한지방대사이상및죽상경화와관련되어있다. 전당뇨병단계에서이미심혈관계질환의위험성이증가하며이에대한예측인자로최근에는혈중아포지질단백에대한관심이커지고있다. ApoB/A-I ratio가지방대사이상과인슐린저항성을평가하는지표일수있으며심혈관계질환의발생을예측하는데있어콜레스테롤보다도유용하다는연구가있다. NAFLD 는인슐린저항성을근간으로하는대사증후군의간내발현으로생각되고있으며대사증후군이심혈관계질환의위험성을증가시키듯 NAFLD 의존재가심혈관계질환의위험인자라는연구결과가보고되고있다. 본연구에서는전당뇨병환자에서 NAFLD와 ApoB/A-I ratio와의연관성을확인하려하였다. 방법 : 2006년부터 2007년까지강북삼성병원건강검진에서전당뇨병으로새롭게진단되어검사참여에동의한 701 명을대상으로바이러스성간염의병력, 주당 30 g 이상의음주력, 지방간을일으킬수있는약물복용력, 당뇨병이나심혈관계질환의병력이있는경우는제외하였다. 복부초음 파를시행하여간지방증을평가하였고, NAFLD 군과대조군의체중, 신장, 체질량지수, 허리둘레, 엉덩이둘레, 수축기및이완기혈압, 간기능검사, 혈중지질검사및혈당검사와혈청검사, 기타심혈관계위험인자를측정하였다. 결과 : 전당뇨병환자중 NAFLD 군은 340명 (48%) 이었다. NAFLD 군과대조군간에유의한차이를보인인구학적, 생화학적인자들은수축기및이완기혈압, 체질량지수, 허리둘레, AST, ALT, 공복인슐린, 공복혈당, HOMA-IR, 총콜레스테롤, 고밀도지질단백, 저밀도지질단백, 중성지방, lipoprotein (a), ApoA-I, ApoB, ApoB/A-I ratio이었다. 남성의경우다형회귀분석으로대사증후군의여러인자인나이, 체질량지수, 허리둘레, HOMA-IR 등을보정하여다변량분석을시행한결과 ApoB/A-I ratio에따라 NAFLD 의유병률이증가함을알수있었다 (OR= % CI=1.007~3.534 and 2.245, 1.215~4.148, and 2.587, 1.389~4.819, 표 3). 여성의경우동일한분석을시행하였을때 NAFLD 와 ApoB/A-I ratio 는유의한상관관계가없었다. 결론 : 전당뇨병남성환자에서 NAFLD 발생은 ApoB/A-I ratio 증가와유의한상관관계가있으며, 이는 NAFLD 가심혈관계질환의위험인자일수있음을시사하므로이에대한전향적연구가필요하다. 중심단어 ; 비알코올성지방간 ; 아포지질단백 B; 아포지질단백 A-I; 전당뇨병 ; 죽상경화증 REFERENCES 1) Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo Sasaki A, Seino Y, Ito C, Shima K, Nonaka K, Kadowaki T. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 55:65-85, ) Diamantopoulos EJ, Andreadis EA, Tsourous GI, Katsanou PM, Georgiopoulos DX, Nestora KC, Raptis SA. Early vascular lesions in subjects with metabolic syndrome and prediabetes. Int Angiol 25: , ) Barter PJ, Rye KA. The rationale for using apoa-i as a clinical marker of cardiovascular risk. J Intern Med 259: , ) Elovson J, Chatterton JE, Bell GT, Schumaker VN, Reuben MA, Puppione DL, Reeve JR Jr, Young NL. Plasma very low density lipoproteins contain a single molecule of apolipoprotein B. J Lipid Res 29: , ) Pitsavos C, Panagiotakos DB, Skoumas J, Papadimitriou L, Stefanadis C. Risk stratification of apolipoprotein B, apolipoprotein A1, and apolipoprotein B/AI ratio on the prevalence of the

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