Original Article JLA The Associations between Alcohol Intake and HDL Cholesterol Subclasses in Korean Population Jung Eun Lim 1, Kim Jung Im 2, Sun Ju Lee 1, Jae Woong Sull 3, Myoungsook Lee 2, Sun Ha Jee 1 1 Department of Epidemiology and Health Promotion, Institute for Health, Promotion, Graduate School of Public Health, Yonsei University, Seoul, 2 Department of Food and Nutrition and Research Institute of Obesity Sciences, Sungshin Women s University, Seoul, 3 Department of Bio-Medical Laboratory Science, Eulji University, Gyeonggi-do, Korea 알코올섭취량과 HDL 콜레스테롤아형과의관련성분석 임정은 1, 김정임 2, 이선주 1, 설재웅 3, 이명숙 2, 지선하 1 연세대학교보건대학원역학건강증진학과, 국민건강증진연구소 1, 성신여자대학교식품영양학과 2, 을지대학교보건과학대학임상병리학과 3 Objective: Alcohol intake has been found to be associated with high-density lipoprotein (HDL) cholesterol. However, the association of alcohol intake with HDL cholesterol subclasses is unclear. Therefore, this study was conducted to determine the association between alcohol intake and HDL cholesterol subclasses among Koreans. Methods: This study included in 1,101 healthy Koreans (men: 765, women: 336) who underwent health check-up at two hospitals in the Korean Cancer Prevention Study 2 (KCPS2). The amounts of alcohol intake were classified into 4 groups: non-, light, moderate, and heavy drinkers (0, <12.5, 12.5-49.9, and 50.0 g/day, respectively). The proportions of HDL cholesterol subclasses were measured after subclasses were identified by 4 30% gradient gel electrophoresis. Multiple regression models were used to estimate regression coefficients after multivariate adjustments. Results: The concentration of HDL, HDL2 and HDL3 significantly increased with increasing amount of alcohol intake. After adjusted for age, body mass index (BMI), waist and smoking status, alcohol consumers of <12.5 g/day, 12.5-49.9 g/day and more than 50.0g/day showed significant positive associations with HDL, HDL2 and HDL3 concentration when compared to non-alcohol drinkers in men. In particular, The strongest positive associations were obtained with HDL2b and HDL3c. Conclusion: HDL2 and HDL3 were significantly associated with increasing amount of alcohol intake in Koreans. In particular, HDL2b among HDL2 and HDL3c among HDL3 showed the strongest positive association with increasing amount of alcohol intake. Key Words: HDL, HDL2, HDL3, Alcohol drinking Received: Revised: Accepted: June 22, 2012 July 24, 2012 July 25, 2012 Corresponding Author: Sun Ha Jee, Department of Epidemiology and Health Promotion, Institute for Health, Promotion, Graduate School of Public Health, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-1523, Fax: +82-2-365-5118, E-mail: jsunha@yuhs.ac * 본연구는보건복지가족부암정복추진연구개발사업지원과 (1220180) 2011 년도정부 ( 교육과학기술부 ) 의재원으로한국연구재단의지원을받았으며 (2011-0029348), 2012 년도정부 ( 교육과학기술부 ) 의재원으로한국연구재단의기초연구사업지원을받아수행된것임 (2012R1A1A1010044). www.lipid.or.kr 61
JOURNAL OF LIPID AND ATHEROSCLEROSIS 서론 한국인의알코올섭취량은점점증가하고있으며 2010년국민건강영양조사에의하면한국인 19세이상성인의연간음주율은 2007년에는 74.2%, 2008년에는 75.5%, 2009년에는 75.7% 이다. 알코올섭취는고혈압및심혈관질환의발생과밀접한관련이있다. 1-3 특히심혈관질환은전세계적으로높은사망률을초래하는고위험질병이다. 4 심근경색증 (myocardial infarction, MI), 관상동맥질환 (coronary heart disease, CHD) 을포함한심혈관계질환위험과알코올섭취간의관계는혈중 high-density lipoprotein (HDL) 콜레스테롤의수준차이에의해중재된다. 5,6 HDL 콜레스테롤의작용기전은콜레스테롤의에스테르화에작용하는 lecithincholesterol acyltransferase의활성을촉진시켜콜레스테롤대사를증가시키고그결과조직내콜레스테롤축적을감소시키며또한항산화작용으로혈관내벽의손상을보호하여혈소판응집을억제시키고 low-density lipoprotein (LDL) 수용체에 LDL 콜레스테롤과경쟁적으로작용하여 LDL 콜레스테롤의재흡수를감소시킨다. 7 HDL 콜레스테롤은크기에따라크기가큰아형군 (HDL2b, HDL2a) 과작은아형군 (preβ1-hdl, HDL3a, HDL3b, HDL3c) 으로분류된다. 8 그동안알코올섭취량과전체 HDL 콜레스테롤농도의관련성에대해서는여러연구가진행되었으나, 9-11 음주정도에따른 HDL 콜레스테롤아형 (HDL2a, HDL2b, HDL3a, HDL3b, HDL3c) 의농도에대한연구는미흡하다. 12 따라서이번연구에서는한국인을대상으로알코올섭취량과 HDL 콜레스테롤아형농도간의관계를살펴보았다. 대상및방법 1. 연구자료및연구대상자 서울경기지역의 7개병원이한국인암예방연구 2 (Korean Cancer Prevention Study 2, KCPS2) 에참여하였는데, 그중신촌세브란스병원과이대목동병원자료를가지고성신여자대학교식품영양학과에서 HDL 콜레스테롤아형분석을하였다. 연구대상은 2006년 4월 25일부터 2010년 6월 30일까지신촌세브란스병원과이대목동병원을내원한한국인 20세이상으로이연구에자발적으로동의한 1,293 명이었다. 전체대상자중에서음주여부 나음주량에대한자료가없는사람 191명과허리둘레값이없는 1명을제외한 1,101 명이최종연구대상자가되었다. 알코올섭취량에따라비섭취군 (0 g/day), 약간마시는군 (<12.5 g/day), 보통마시는군 (12.5-49.9 g/day), 많이마시는군 ( 50.0 g/day) 으로분류하였다. 13 설문자료수집은인구사회학적특성, 흡연력, 음주력, 운동습관, 과거력, 약복용력등을포함하였다. 흡연여부는비흡연, 과거흡연, 현재흡연으로구분하였다. 음주여부는음주 ( 현재음주, 과거음주포함 ), 비음주로구분하였으며양과빈도를포함하였다. 키와몸무게는병원에서제공한가벼운소재의상하의를입은채직접측정하였으며체질량지수 (Body Mass Index, BMI) 는체중 (kg)/ 키 (m) 2 로계산하였다. 허리둘레는줄자를이용하여수검자들이속옷만을입은상태에서허리를노출시킨채흉골과장골능사이의가장오목한부분을수평으로측정하였다. 혈압은수은주혈압계나자동혈압계를이용하여직접측정된자료를수집하였다. 혈액은밤새공복을한상태에서오전에수집되었다. 혈액검사는총콜레스테롤, 중성지방, LDL 콜레스테롤, HDL 콜레스테롤, 공복혈당을포함하였다. 2. HDL 콜레스테롤아형분석 600 μm의혈청을 4 o C에서하루이상보관하여녹인후에 1.063<d<1.478 g/ml의 density solution을이용하여 1,050,000 X g RCF로 140분동안원심분리 (Hitachi CS150GXL,S140AT fixed angle rotor, Japan) 하여상층액에서 HDL 콜레스테롤을걸러내고, 그후 10 μl의 HDL 콜레스테롤을 4-30% polyacrylamide non-denaturation gradient gel (LPE gels 4/30, CSI Scientific, CA, USA) 에로딩하여 Pore Gradient Lipoprotein electrophoresis (PGGE, CSI Scientific Electrophoresis LPE-4003;C.B.S.Scientific Inc., Solana Beach, CA, USA) 를하였다. 80V로 20분동안 pre-run 한후에 100V로 2시간, 130V로 4시간, 150V 로 18시간, 120V 로 2시간가동하였다. 겔을 Coomassie Blue G-250으로염색하였고마커 (thyroglobulin, 17 nm; ferritin,12.2 nm; ctalase,10.4 nm; LDH, 8.2 nm; BSA,7.1 nm; Amersham, GE Healthcare, UK) 를이용하여 Image-Master ID software 4.0(Amersham Pharmacia Biotech, USA) 로분석하였다. 다음과같은크기구간으로 HDL 콜레스테롤을각아형별로분류하였다. : HDL3c, 7.2-7.8 nm; HDL3b, 7.8-8.2 nm; HDL3a, 8.2-8.8 nm; HDL2a, 62 www.lipid.or.kr
Jung Eun Lim, et al: Alcohol Intake and HDL Cholesterol Subclasses Table 1. The characteristics of the study population Characteristics Men (N=765) Women (N=336) Age, years 47.7±10.8 43.5±10.9 Body mass index, kg/m 2 24.7±2.8 22.6±3.2 Total Cholesterol, mg/dl 194.2±33.0 183.9±34.2 Triglyceride, mg/dl 145.9±94.2 91.9±51.5 Waist circumference, cm 87.1±7.9 75.9±9.1 Alcohol intake, g/day 21.0±28.1 5.5±12.5 LDL cholesterol, mg/dl 119.8±29.6 107.1±29.0 HDL cholesterol, mg/dl 49.1±10.6 59.6±14.3 HDL2a, % 20.9±1.2 21.0±1.6 HDL2b, % 36.0±3.4 38.4±3.7 HDL3a, % 16.7±1.2 16.2±1.2 HDL3b, % 11.2±1.3 10.4±1.4 HDL3c, % 15.2±2.4 14.1±2.3 HDL2a, mg/dl 10.3±2.3 12.5±3.2 HDL2b, mg/dl 17.8±4.8 23.1±6.8 HDL3a, mg/dl 8.1±1.7 9.6±2.2 HDL3b, mg/dl 5.4±1.1 6.1±1.3 HDL3c, mg/dl 7.4±1.9 8.3±2.1 Smoking status Current smokers 49.41% 6.85% Ex-smokers 33.07% 2.98% None smokers 17.52% 90.18% HDL: high density lipoprotein, LDL: low-density lipoprotein. 103 participants in men and 155 participants in women have missing for alcohol intake Mean±SD 8.8-9.7 nm; HDL2b, 9.7-12.2 nm. 8 3. 통계분석각변수간의상관성은 Pearson 상관계수를이용하였으며, 알코올섭취량과 HDL 콜레스테롤의관계를보기위해다중회귀분석을하였다. 그리고알코올섭취량에따른 HDL2b(%) 변화에연령, BMI, 허리둘레, 흡연유무가미치는영향을살펴보기위해분산분석과로지스틱회귀분석을하였다. 모든분석은 SAS 버전 9.2 소프트웨어패키지를이용하여이루어졌다 (SAS Institute Inc, Cary, NC, USA). 다음과같다 (Table 1). HDL 콜레스테롤평균농도가남자 49.1 mg/dl, 여자 59.6 mg/dl이었으며, 그중 HDL2b 가차지하는비율은남녀각각평균 36.0%, 38.4% 이었고하루평균알코올섭취량은남자는 21.0 g (1.8 drink), 여자는 5.5 g (0.5 drink) 이었다. 14 남자에게서총 HDL 콜레스테롤에 HDL2b가차지하는비율 (%) 은연령, 알코올섭취량, 총 HDL 콜레스테롤과양의관련성을보였고, 체질량지수, 허리둘레, 수축기혈압, 총콜레스테롤, 중성지방, LDL 콜레스테롤과음의관련성을보였다. 그리고남자에게서 HDL2b 의농도 (mg/dl) 는총 HDL 콜레스테롤과양의관련성 을보였고, 체질량지수, 허리둘레, 공복혈당, 중성지방, LDL 콜레 결과 연구대상은남자 765 명과여자 336 명이었으며일반적특성은 스테롤과음의관련성을가졌다 (Table 2). 여자에게서연령, 체질량지수, 알코올섭취량, 허리둘레, 공복혈당, 수축기혈압, 총콜레스테롤, 중성지방, LDL 콜레스테롤, www.lipid.or.kr 63
JOURNAL OF LIPID AND ATHEROSCLEROSIS Table 2. Correlations between high-density lipoprotein (HDL) subclasses levels and basic variables in men (%) (mg/dl) HDL2a HDL2b HDL3a HDL3b HDL3c HDL2a HDL2b HDL3a HDL3b HDL3c Alcohol intake, g/day -0.039 0.123* -0.086* -0.123* -0.047 0.069 0.108* 0.049 0.002 0.030 Fasting Blood Sugar, mg/dl 0.006-0.096* 0.066 0.133* 0.029-0.038-0.065-0.018 0.037-0.010 Systolic blood pressure, mmhg 0.004-0.041-0.030 0.042 0.051 0.113* 0.083* 0.111* 0.141* 0.127* Total Cholesterol, mg/dl 0.087* -0.132* 0.069 0.095* 0.058 0.197 0.010* 0.217 0.237 0.188 Triglyceride, mg/dl -0.046-0.217-0.000 0.243 0.201-0.291-0.303-0.301-0.155-0.116* LDL cholesterol, mg/dl 0.134* -0.141* 0.176 0.080* 0.003 0.077* -0.023 0.111* 0.097* 0.043 HDL cholesterol, mg/dl -0.041 0.325-0.332-0.306-0.111 0.963 0.936 0.943 0.823 0.756* Adjusted for age, BMI, waist and smoking status HDL: high density lipoprotein, LDL: low-density lipoprotein *: P value<0.05 : P value <0.0001 Table 3. Correlations between high-density lipoprotein(hdl) subclasses levels and basic variables in women (%) (mg/dl) HDL2a HDL2b HDL3a HDL3b HDL3c HDL2a HDL2b HDL3a HDL3b HDL3c Alcohol intake, g/day 0.144 0.030-0.097-0.066-0.091 0.189* 0.123 0.127 0.113 0.058 Fasting Blood Sugar, mg/dl -0.073-0.019-0.025 0.057 0.072 0.002 0.021 0.023 0.059 0.064 Systolic blood pressure, mmhg 0.094-0.010 0.066 0.113-0.017 0.175* 0.101 0.176* 0.203* 0.106 Total Cholesterol, mg/dl -0.095-0.048-0.021 0.040 0.151* 0.297 0.285* 0.380 0.394 0.403 Triglyceride, mg/dl -0.026-0.342 0.171* 0.354 0.286-0.331-0.403-0.331-0.183* -0.141 LDL cholesterol, mg/dl -0.078-0.192* 0.172* 0.189* 0.196-0.059-0.098 0.025 0.089 0.096 HDL cholesterol, mg/dl 0.019 0.281* -0.314-0.331-0.127 0.925 0.936 0.959 0.818 0.778 Adjusted for age, BMI, waist and smoking status HDL: high density lipoprotein, LDL: low-density lipoprotein *: P value<0.05 : P value <0.0001 총 HDL 콜레스테롤과 HDL 콜레스테롤아형과의상관관계를살펴본표에서는, 총 HDL 콜레스테롤에 HDL2b 가차지하는비율 (%) 이총 HDL 콜레스테롤과양의관련성을보였고, 체질량지수, 허리둘레, 공복혈당, 수축기혈압, 중성지방, LDL 콜레스테롤과음의관련성을보였다 (Table 3). 여자에게서 HDL2b의농도는총콜레스테롤, 총 HDL 콜레스테롤과양의관련성을보였고, 연령, 체질량지수, 허리둘레, 공복혈당, 수축기혈압, 중성지방, LDL 콜레스테롤과음의관련성을가졌다. 남자에게서알코올섭취량에따른 HDL 콜레스테롤아형별변화를나타내어보면 Table 4와같다. 연령, 체질량지수, 허리둘레, 흡연상태를통제하였을때, 알코올섭취량이 0 g/day 인군을기준으로섭취량이 <12.5 g/day, 12.5-49.9 g/day, 50.0 g/day 이상으로증가할수록알코올섭취량에대한 HDL, HDL2, HDL3 의회귀계수값이모두유의하게증가하는경향을보였다. HDL2를 HDL2a와 HDL2b로구분하고, HDL3을 HDL3a, HDL3b, HDL3c 로나누어살펴본결과, HDL2a 와 HDL3b 를제외한모든아형군에서알코올섭취량에대한회귀계수값이통계적으로유의하게증가하였다. Fig. 1은알코올섭취량에따른 HDL2b (mg/dl) 의변화에연령 (50세미만, 50세이상 ), 체질량지수 (25 kg/m 2 미만, 25 kg/m 2 이상 ), 허리둘레 (85 cm 미만, 85 cm 이상 ), 흡연유무가영향을미치는지를살펴본것이다. 알코올섭취량에따른 HDL2b (mg/dl) 변화에연령, 체질량지수, 허리둘레, 흡연유무모두유의한영향을미치지못했다 (Fig. 1, P >0.05). 64 www.lipid.or.kr
Jung Eun Lim, et al: Alcohol Intake and HDL Cholesterol Subclasses Table 4. Regression analysis between alcohol intake and high-density lipoprotein (HDL) subclasses levels (mg/dl) in men 0 N=102 alcohol consumption (g/day) <12.5 N=360 12.5-49.9 N=209 50.0 N=94 P for trend R 2 ΔR 2 HDL unadjusted 0.0 2.8 2.1 3.9 0.0670 0.0102 adjusted 0.0 3.2 3.9 6.7 < 0.0001 0.1369 HDL2 unadjusted 0.0 1.1 0.7 2.1 0.1133 0.0068 adjusted 0.0 1.4 1.9 4.0 < 0.0001 0.1411 HDL2a unadjusted 0.0 0.8 0.4 0.9 0.1530 0.0155 adjusted 0.0 0.8 0.7 1.4 < 0.0001 0.1378 HDL2b unadjusted 0.0 0.4 0.3 1.3 0.1072 0.0052 adjusted 0.0 0.6 1.1 2.6 < 0.0001 0.1390 HDL3 unadjusted 0.0 1.7 1.4 1.7 0.0480 0.0176 adjusted 0.0 1.8 2.0 2.7 < 0.0001 0.1054 HDL3a unadjusted 0.0 0.7 0.3 0.6 0.2519 0.0195 adjusted 0.0 0.6 0.6 1.0 0.0003 0.1400 HDL3b unadjusted 0.0 0.6 0.4 0.5 0.1601 0.0300 adjusted 0.0 0.6 0.5 0.7 0.0012 0.0941 HDL3c unadjusted 0.0 0.5 0.7 0.6 0.0071 0.0131 adjusted 0.0 0.6 0.9 1.0 < 0.0001 0.0691 Adjusted for age, BMI, waist and smoking status 0.0247 0.0215 0.0240 0.0207 0.0273 0.0232 0.0293 0.0258 Fig. 1. HDL2b (mg/dl) differences according to age, BMI, waist and smoking status. All figures are adjusted for sex, age, BMI, waist and smoking status except relevant variable. www.lipid.or.kr 65
JOURNAL OF LIPID AND ATHEROSCLEROSIS 고찰 본연구에서알코올섭취량이증가할수록 HDL2, HDL3의농도가높아진다는결론을얻었다. 특히, 알코올섭취량이증가할수록 HDL2에서는 HDL2b, HDL3에서는 HDL3c의농도가가장뚜렷이증가하는관련성을보였다. 동시에이전연구에서알려진총 HDL 콜레스테롤과알코올섭취량의양의관련성을재확인하였다. 9-11 HDL2가 HDL3보다알코올의섭취량이 12.5 g/day 미만에서 12.5 g/day 이상 50.0 g/day 미만, 50.0 g/day 이상으로증가할수록더강하게증가하는관련성을보여주었고특히, HDL2 중에서도 HDL2b가뚜렷하게증가하였다. 한편, HDL2a는알코올비섭취군을기준으로각각회귀계수값이알코올을약간섭취하는군 (12.5 g/day 미만 ) 에서 0.8, 알코올중간수준섭취군 (12.5 g/day 이상 50.0 g/day 미만 ) 에서 0.7, 알코올고섭취군 (50.0 g/day 이상 ) 에서 1.4로얻어졌고알코올섭취량이증가함에따라통계적으로유의하게증가하였다 (Table 4, P for trend <0.0001). 마찬가지로 HDL3b는알코올비섭취군을기준으로하였을때, 회귀계수값이알코올을약간섭취하는군 (12.5 g/day 미만 ) 에서 0.6, 알코올중간수준섭취군 (12.5 g/day 이상 50.0 g/day 미만 ) 에서 0.5, 알코올고섭취군 (50.0 g/day 이상 ) 에서 0.7로얻어졌고알코올섭취량이증가함에따라통계적으로유의하게증가하였다 (Table 4, P for trend<0.0001). 알코올섭취와각각의 HDL 콜레스테롤아형농도에대한몇가지연구가있었으나통일된결과를보여주지못했다. 본연구와유사한연구결과로는알코올을 0-5 g/day 섭취하는그룹에비하여 30.1-75 g/day 섭취하는그룹에서 HDL2b 가 28%, HDL2a가 37%, HDL3 는 11% 증가하였다는결과가있었다. 15 하지만기존연구에서는 HDL3을아형별로더세분화하지않아 HDL3a, HDL3b, HDL3c 가알코올섭취량이증가함에따라어떻게변하는지는알수없었다. 한편, 다른연구에서알코올섭취량이 HDL3 의농도와는양의관련성을보였으나 HDL2와는유의한관련성을보이지않았다는결과가발표되기도하였고, 16 반대로알코올을과량섭취한군이비섭취군에비하여 HDL2 농도가 22%(P=0.025) 증가하고 HDL3 은유의한차이가없었다는보고도있었다. 17 HDL 콜레스테롤의정량적변화는간에서의생산증가나 apoa-i과 apoa-ii의운반율증가로보인다. 6,18 알코올은 cholesteryl ester transfer protein (CETP) 의활성을방해하여 HDL로부터 LDL 로콜레스테롤을운반하는것에영향을주어 HDL 수치를높인다. 높은알코올섭취가 CEPT의활성을억제하고이것이 HDL3b를증가시킨다. 19 또한알코올유도성 phospholipid transfer protein (PLTP) 의활성은인지질을중성지방함량이높은지질단백으로부터 HDL로옮기는기능을하여, HDL2b 를증가시킨다. 20 HDL 콜레스테롤아형과심장병에관하여서는여러 population study에서 HDL2가 HDL3보다더강한심장보호효과를보인다고보고되었다. 21,22 하지만연구대상자의차이에따라다른연구에서는 HDL2 와 HDL3 가동일한심장보호효과를보였다는보고도있었다. 23 본연구는데이터를수집함에있어 HDL 콜레스테롤아형을기존대부분의연구에서 HDL2, HDL3로만구분한것과달리, 16-17 HDL2a, HDL2b, HDL3a, HDL3b, HDL3c로자세히분류하여측정하였다는장점이있고, 종합검진센터에서검진방법을교육받은검진전문가에의해자료가수집되었다는장점이있다. 또한한국인을대상으로하여다른나라들보다특히알코올남용의비율이높은한국인의특성을잘반영하였다는장점이있다. 한편, 본연구는단면연구라결과해석에제한점이존재하고, HDL 콜레스테롤을여러번측정하여평균값을사용하지않고 1회측정값을사용하여서측정오차가존재할수있다는한계점이있다. 또한서로다른두개의병원에서수집된자료라총콜레스테롤, 중성지방, HDL 콜레스테롤, 헤모글로빈, 공복시혈당측정에차이가있을수있으나대한정도관리학회에서시행한외부정도관리분석결과검사방법별병원간상관성은모두 0.98 이상으로매우높은상관성을보였으므로결과에영향을미치지않았다. 결론적으로연령, 체질량지수, 허리둘레, 흡연상태를보정하였을때, 알코올섭취량이증가할수록총 HDL 콜레스테롤과 HDL2, HDL3의농도 (mg/dl) 가증가하였고, 특히이러한관련성은 HDL2b 와 HDL3c 에서강했다. 앞으로알코올이 HDL 콜레스테롤아형의농도변화에미치는영향에대한여러코호트연구들이필요하고동시에알코올섭취가 HDL 아형의농도변화를일으키는생물학적기전을밝히는연구도진행되어야겠다. 참고문헌 1. Taylor B, Irving HM, Baliunas D, Roerecke M, Patra J, 66 www.lipid.or.kr
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