<31322EB9DAC1BEB7FC2E687770>

Size: px

Start display at page:

Download "<31322EB9DAC1BEB7FC2E687770>"

시현 주
5 years ago
Views:

1 대한내과학회지 : 제 74 권제 4 호 2008 제 2 형당뇨병환자에서스타틴치료시 HDL 콜레스테롤의변화 메리놀병원내과 1, 인제대학교의과대학내과학교실 2, 백인제임상의학연구소 3 박종률 1 장혜정 1 문정윤 1 석지혜 1 김미경 1, 3 박정현 2, 3 이병두 2 The effect of statins on HDL-cholesterol in type 2 diabetic patients Jong-Ryul Park, M.D. 1, Jang Hye Jung, M.D. 1, Jung Youn Moon, M.D. 1, Ji-Hye Suk, M.D. 1, Mi Kyung Kim, M.D. 1, 3, Jeong Hyun Park, M.D. 2, 3 and Byung Doo Rhee, M.D. 2 Department of Internal Medicine, Maryknoll General Hospital, Busan, Korea 1 ; Department of Internal Medicine, College of Medicine, Inje University, Busan, Korea 2 ; Paik Memorial Institute for Clinical Research, Pusan Paik Hospital, Inje University, Busan, Korea 3 Background/Aims : Statins have been a mainstay of treatment for primary and secondary prevention of coronary heart disease through their beneficial effect on lipid profile. However, their effect on the HDL cholesterol level has been determined to be equivocal or unclear. This study sought to investigate HDL cholesterol response to statin treatment in type 2 diabetic patients. Methods : We retrospectively assessed the effect of statins in 217 patients with type 2 diabetes and dyslipidemia through chart review. Patients who were using medications such as fibrates, niacin, or thiazolidinediones, or had a plasma creatinine concentration greater than 1.5 mg/dl, a fasting triglyceride level greater than 300 mg/dl, or chronic liver disease, were excluded from the study. Result : The mean level of LDL cholesterol was significantly decreased, and the percentage of patients who achieved the normal LDL cholesterol level was increased in this study. The mean HDL cholesterol level after statin treatment was decreased by 2.3%. The percent change of HDL cholesterol was affected by baseline HDL cholesterol level, percent change of total cholesterol, percent change of LDL cholesterol, and baseline total cholesterol level. When subjects were divided into quintiles according to baseline HDL cholesterol, HDL cholesterol level was found to be increased in the lowest two quintiles while it was decreased in the highest two quintiles. Conclusions : There were some patients whose HDL cholesterol level was decreased after statin treatment, depending on their baseline HDL cholesterol level. We think further study on the effect of statins on HDL level will be needed in the future. (Korean J Med 74: , 2008) Key Words : Statin; HDL cholesterol; Type 2 DM 서 동맥경화증의예방과심혈관질환의감소을위하여많 론 은약제가개발되어왔고새로운치료방법이연구되어왔다. 그중스타틴은가장빠르게발전해온약제의하나로서여러가지대규모연구에서심혈관질환감소에대한그의 Received : Accepted : Correspondence to : Mi Kyung Kim, M.D., Department. of Internal medicine, Maryknoll General Hospital, 4-12 Daecheong-dong, jung-gu, Busan , Korea kmkdoc@yahoo.co.kr

2 - The Korean Journal of Medicine : Vol. 74, No. 4, 효과가증명되어오면서대부분의경우에심혈관질환예방과치료를위한주된약으로선택되어왔다 1-4). 심혈관질환의유병률과사망률이일반인보다훨씬높은당뇨병의이상지혈증치료에서도주로스타틴이일차선택제로사용되고있다. 일반적으로스타틴제제는 LDL 콜레스테롤을 18~55%, 중성지방을 7~30% 정도감소시키고 HDL 콜레스테롤을 5~15% 정도증가시키는것으로알려져있어 LDL 콜레스테롤에비해 HDL 콜레스테롤에대한효과는상대적으로약한것으로생각된다 5). 그러나 Framingham Heart Study 결과 HDL 콜레스테롤감소는심혈관질환발생위험성의가장강력한예측인자였으며미국의 4개전향적연구를종합분석한결과에서는 HDL 콜레스테롤이 1 mg/dl 증가할때마다심혈관질환의발생이 2~3% 씩감소하는것으로나타나 HDL 콜레스테롤의적절한조절또한중요하다고알려진다 6, 7). 이전에시행된몇몇대규모연구를종합할때스타틴을치료하면 HDL 콜레스테롤은그리크게증가하지크지않았으며특히제2형당뇨병환자만을대상으로분석한연구에서는 HDL 콜레스테롤을올리는데미미한효과를보였다 3, 4). 올해한연구에서는스타틴치료를받고있는 3,900여명의제 2형당뇨병환자와 4,500여명의당뇨병이아닌환자를비교하였을때, 당뇨병환자에서는스타틴치료에도불구하고낮은 HDL cholesterol 수치를가진환자가흔하다고발표하였다 8). Pravastatin 치료후 HDL 콜레스테롤의변화를관찰한대규모연구에서전체적으로 HDL 콜레스테롤이평균 8.3% 증가함이관찰되었지만적지않은환자에서 HDL 콜레스테롤이오히려감소하였고, 스타틴치료후의 HDL 콜레스테롤의변화는상당한개인적차이가있는것으로보고되었다 2). 이에본연구는제2형당뇨병환자에서스타틴치료시 HDL 콜레스테롤혈중수치변화에대해분석하고자시행되었다. 대상및방법 1. 연구대상메리놀병원내분비내과에서치료중인 30세에서 70세사이의제2형당뇨병환자중처음으로스타틴을사용한환자를대상으로하였다. 다른지질강하제인피브린산유도체 (fibrate) 나니코틴산 (niacin) 을사용하는환자, thiazolidinedione을사용하고있는환자, 크레아틴이 1.5 mg/dl 이상, 중 성지방이 300 mg/dl 이상인경우, 그리고만성간질환이있는경우는연구대상에서제외하였다. 스타틴치료의시작과용량조절은표준지질치료지침에따라내분비내과분과전문의에의해처방되었다. 2. 방법진료기록부를근거로각환자들의스타틴치료전후총콜레스테롤, 중성지방, HDL 콜레스테롤, LDL 콜레스테롤, 당화혈색소를조사하였고, 치료전후신장과체중을조사하였고, 체중 (kg) 을신장 (m) 의제곱으로나누어체질량지수 (kg/m 2 ) 를계산하였다. 지질검사는생화학자동분석기 (Hitachi , Hitachi co. Japan) 을이용하여효소법으로측정되었고, 당화혈색소치는 high performance liquid chromatography (Bio-rad) 로측정되었다. 스타틴의종류는 simvastatin 20 mg, atorvastatin 10 mg, fluvastatin 40 mg, lovastatin 20 mg이사용되었다. 모든자료는평균 ± 표준편차로표시하였고, 통계학적검증은 SPSS version 12.0 을이용하였다. 스타틴투약전후의변화는 paired t-test로비교하였고, 스타틴치료후 HDL 콜레스테롤에영향을주는인자들은 correlation과 multiple linear regression model을이용하여분석하였다. 유의수준은 p<0.05 로하였다. 결과 1. 연구대상환자의임상적특징및스타틴치료후체질량지수, 당화혈색소의변화총대상환자수는 217명으로남자는 75명, 여자는 142명이며평균연령은 60세였다 ( 표 1). 스타틴을사용한기간은평균 11개월이었으며, 최저 3개월이상, 최고 28개월이었다. 체질량지수는치료전후 24.9 kg/m 2 에서 25.1 kg/m 2 로통계적으로의미있게증가되었고, 당화혈색소는치료전 8.2± 1.9% 에서 7.7±1.4% 로의미있게감소하였다 ( 표 1). 2. 스타틴치료후혈청지질의변화혈중총콜레스테롤과 LDL 콜레스테롤, HDL 콜레스테롤은치료후각각평균 24.1%, 34.1%, 2.3% 감소되었으며중성지방은유의한변화가없었다 ( 표 1). 3. 스타틴치료에대한 LDL 콜레스테롤의변화 LDL 콜레스테롤은스타틴치료전 145±32 mg/dl 에서치

3 - Jong-Ryul Park, et al : The effect of statins on HDL-cholesterol level - Table 1. Baseline characteristics of study subjects and changes in BMI, lipid profile, and HbA1c after statin treatment Clinical characteristics and Parameter Baseline After statin treatments p-value* Age (years) Male : Female (number) Body mass index (kg/m 2 ) Total cholesterol (mg/dl) LDL-cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) HbA1c (%) 60±10 75 : ± ±39 145±32 141±59 48±12 8.2± ± ±33 92±26 140±85 46±10 7.7±1.4 Values are means±standard deviations. * p-values are calculated by paired-t test between baseline and after statin treatment Table 2. Changes in number of patients having ideal levels of LDL and HDL cholesterol after statin treatment Patient with LDL-C 100 mg/dl Male patient with HDL-C 40 mg/dl Female patient with HDL-C 50 mg/dl Data are number of patients (%) Baseline 15 (6.9%) 55 (73.3%) 72 (50.7%) After statins treatments 142 (65.4%) 45 (60.8%) 57 (40.1%) A B C LDL-C 1 (n=43) 2 (n=43) 3 (n=43) 4 (n=43) 5 (n=45) Mean baseline (mg/dl) Percent fall (%) Absolute fall (mg/dl) Figure 1. LDL cholesterol response to statin treatment. A, the distribution of LDL cholesterol levels at baseline. B, percent change in LDL cholesterol from baseline to follow-up. C, Percent and absolute change in LDL cholesterol when divided into quintiles

- 대한내과학회지 : 제 74 권제 4 호통권제 572 호 2008 - A B C HDL-C 1 (n=43) 2 (n=43) 3 (n=43) 4 (n=43) 5 (n=45) Mean baseline (mg/dl) 34 42 48 53 65 Percent increase (%) 13.0 3.3-3.8-10.6-13.

B, percent change in HDL cholesterol from baseline to follow-up. C, Percent and absolute change in HDL cholesterol when divided into quintiles. Table 3.

4 - 대한내과학회지 : 제 74 권제 4 호통권제 572 호 A B C HDL-C 1 (n=43) 2 (n=43) 3 (n=43) 4 (n=43) 5 (n=45) Mean baseline (mg/dl) Percent increase (%) Absolute increase (mg/dl) Figure 2. HDL cholesterol response to statin treatment. A, the distribution of HDL cholesterol levels at baseline. B, percent change in HDL cholesterol from baseline to follow-up. C, Percent and absolute change in HDL cholesterol when divided into quintiles. Table 3. Correlation between the percent change in HDL cholesterol and other factors after statin treatment Sex (male) Age Body mass index HbA1c Baseline Total cholesterol Baseline Triglyceride Baseline HDL-cholesterol Baseline LDL-cholesterol % change of Total cholesterol % change of Triglyceride % change of LDL-cholesterol r * * * * * p-value 료후 92±26 mg/dl 로 34.1% 감소하였다 ( 표 1). LDL 콜레스테롤수치가 100 mg/dl 이하인사람은치료전 15명 (6.9%) 에서치료후 142명 (65.4%) 으로증가하였다 ( 표 2). 치료전 LDL 콜레스테롤수치에따라 5 분위수로나누어 LDL 콜레스테롤의퍼센트변화를분석하였을때수치가제일낮은첫번째분획에서는 12.6% 의감소를보였고, 나머지네분획에서는 32.1% 에서 43.2% 감소를보였다 ( 그림 1). 4. 스타틴치료에대한 HDL 콜레스테롤의변화 HDL 콜레스테롤은스타틴치료전 48±12 mg/dl 에서치료후 46±10 mg/dl 로평균 2.3% 감소하였다 ( 표 1). 남자 75 명중 HDL 콜레스테롤수치가 40 mg/dl 이상인사람은치료전 55명 (73.3%) 에서치료후에는 45명 (60.8%) 으로감소하였다. 여자 142명중 HDL 콜레스테롤수치가 50 mg/dl 이상인사람은치료전 72명 (50.7%) 에서치료후 57명 (40.1%) 로감소하였다 ( 표 2). 치료전 HDL 콜레스테롤수치에따라 5분위수로나누어 HDL 콜레스테롤의퍼센트변화를분석하였을때수치가상

5 - 박종률외 6 인 : 스타틴치료후 HDL 콜레스테롤수치의변화 - Table 4. Predictors of percent increase in HDL cholesterol after statin treatment β p-value * Baseline HDL-Cholesterol % change of Total cholesterol % change of LDL-cholesterol Baseline Total cholesterol Corrected R square=0.560 p values are calculated by multiple linear regression analysis 대적으로낮은두분획에서는치료후각각 13%, 3.3% 증가하였고, 수치가상대적으로높은세분획에서는각각 3.8%, 10.6%, 13% 감소하였다 ( 그림 2). HDL 콜레스테롤의퍼센트변화는치료전총콜레스테롤, LDL 과 HDL 콜레스테롤수치, 총콜레스테롤과 LDL 콜레스테롤의퍼센트변화와의미있는상관관계를보였으며그중치료전 HDL 콜레스테롤수치가가장강력한음의상관관계를보였다 ( 표 3) (r= , p). 성별, 나이, 체질량지수, 중성지방, 당화혈색소등은 HDL 콜레스테롤의퍼센트변화와의미있는상관관계를보이지않았다 ( 표 3). 치료전 HDL 콜레스테롤수치에따라 5분위수로나누어서체질량지수의변화를분석하였을때, 각각 0.49±2.3, 0.14± 1.28, 0.20±1.08, 0.24±1.68, 0.17±1.10 kg/m 2 로통계적으로의미있는차이는없었다 (p value=0.86). 다중회귀분석에서 HDL 콜레스테롤의퍼센트변화에영향을미치는인자는치료전 HDL 콜레스테롤수치, 총콜레스테롤과 LDL 콜레스테롤의퍼센트변화와치료전총콜레스테롤수치였다 ( 표 4)(corrected R 2 =0.560). 고찰스타틴치료시심혈관질환의일차적, 이차적예방효과는여러가지대규모임상연구와제2형당뇨병환자만을대상으로한연구에서비슷하게증명되었고, 이러한효과는이들약물이 lipid profile, 특히 LDL 콜레스테롤에긍정적인효과를보이기때문으로분석되고있다 3, 4). 본연구에서도제2 형당뇨병환자에서스타틴치료시 LDL 콜레스테롤은평균 34.1% 감소하였고, 당뇨병환자에서의목표인 LDL 콜레스테롤수치 100 mg/dl 이하에도달한사람이치료전 15명 (6.9%) 에서치료후 142명 (65.4%) 으로현저하게증가되었다. 스타틴은일반적으로 HDL 콜레스테롤을중등도로 (5~ 15%) 증가시키는것으로보고되어있으나이에대한기전은확실히알려져있지않다 5). 스타틴이혈중의 Cholesterol Ester Transfer Protein (CETP) 를감소시켜 HDL 콜레스테롤을증가시키거나, HDL 콜레스테롤의주요성분인아포지단백 A-I 의생성을증가시킨다는보고가있어이것이일부기전으로관여하는것으로생각되고있다 9, 10). 그러나제2형당뇨병환자만을대상으로한 the Collaborative Atorvastatin Diabetes Study (CARDS) 와 Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA) 에서연구기간동안 atorvastatin 복용후 HDL 콜레스테롤이각각 53.7 mg/dl 에서 48.6 mg/dl, 47.9 mg/dl에서 47.1 mg/dl로치료전에비해변화가없거나감소하였으며위약군에비해의미있는증가를관찰할수없었다 3, 4). 또한여러스타틴제제를용량별로나누어그효과를비교한연구에서용량이증가하면서 HDL 콜레스테롤증가효과가감소하고스타틴종류에따라서도차이가보임을보고하였다 11). 본연구에서제2 형당뇨병환자에서스타틴치료시 HDL 콜레스테롤은평균 2.3% 감소하였다. 치료전 HDL 콜레스테롤수치에따라 5분위수로나누었을때, 수치가상대적으로낮은두분획에서는치료후각각 13%, 3.3% 증가하였고, 수치가상대적으로높은세분획에서는각각 3.8%, 10.6%, 13% 감소함을보였다. LDL 콜레스테롤의경우에는대조적으로치료전수치에따른분획에관계없이스타틴치료후감소되는퍼센트변화율이비슷하였다. 이렇게치료전 HDL 콜레스테롤농도에따라스타틴치료시변화폭이다르고, 평균치의변화에서기대하는것과달리처음보다그수치가낮아지는대상들이있다는것은다른연구에서도관찰할수있었다. 건강검진으로이상지혈증이발견된 2,880명의환자에서 pravastatin 치료후대략 20% 의환자에서 HDL 콜레스테롤감소가관찰되었고, 기저 HDL 콜레스테롤에따라 5개의분획으로나누었을때기저값이가장낮은군에서는스타틴치료후 HDL 콜레스테롤상승률이 11.9% 였으나기저값이가장높은군에서는 5.1% 로본연구와같이음의상관관계를보였다 12). 스타틴은 apo B를가지고있는지단백들모두

6 - The Korean Journal of Medicine : Vol. 74, No. 4, 에영향을미치기때문에스타틴치료후변하는 HDL 콜레스테롤수치가여러가지대규모연구에서심혈관질환의위험을감소시킨다고알려진스타틴의전체적인효과에어느정도기여하는지는알기어렵다고알려져있어 13) 이에관해향후더많은연구가필요하리라고생각된다. HDL 콜레스테롤은흡연, 알코올, 비만, 운동, 식이, 약제등의다양한환경적인자에영향을받지만 6), 최근연구에의하면 HDL 콜레스테롤수치의개인차의 40% 가유전적인차이에의해결정되는것으로추정하고있다 14-16). 약제에대한반응또한유전적인영향을받으며, 후보유전자로는 CETP 유전자의이형성, apo A1 프로모터의이형성등과의관련성이보고되고있다 17, 18). West of Scotland Coronary Prevention Study (WOSCOPS) 에서 pravastatin 치료후 HDL 콜레스테롤의변화에미치는인자를분석한연구에서치료전 HDL 콜레스테롤수치, 치료전중성지방수치와중성지방의감소정도, 체질량지수에따라 HDL 콜레스테롤의증가에차이를보이는것으로보고하였다 12). 본연구에서제2 형당뇨병환자에서스타틴치료시 HDL 콜레스테롤의퍼센트변화는치료전 HDL 콜레스테롤수치와가장강력한음의상관관계를보였으며체질량지수, 중성지방수치는의미있는상관관계를보이지않았다. 본연구에서는중성지방수치가높은환자들이대상에서제외되어치료전중성지방수치가높지않고치료후유의한변화가관찰되지않았기때문에중성지방수치와의관련성을보이지않은것으로생각된다. 본연구의제한점은첫째, 본원을내원했던환자들만을대상으로하여분석이시행되었으므로이러한결과가모든당뇨병환자를대표할수는없을것이다. 둘째, 후향적연구이므로약제의효과를바르게평가하기는어렵고, 환자들의순응도, HDL 콜레스테롤에영향을줄수있는 β차단제, 메트폴민등의약제및식이나운동, 알코올, 흡연등의생활습관의차이로인한영향을배제하기어렵다. 개개인의약제변화에대해서는연구시점에서일일이분석하기는어려워약제변화에따른지질수치의변화도있을수있으나, 대부분의환자들에서는당뇨치료약제사용에있어서는큰변화가없었고, 크게영향을끼칠수있는 fibrate 나니코틴산, thiazolidinedione을사용하고있는환자는연구대상에서제외하였다. 셋째, 본연구에서이전연구와달리스타틴치료후중성지방은거의감소되지않았는데, 이는환자선택시중성지방이높은환자들은피브린산유도체를병용투여한경우가많아중성지방이높은군을제외시키면서치료전 평균중성지방의수치가높지않았고, 이로인해중성지방의감소로인한 HDL 콜레스테롤의증가를보지못했을가능성이있다. 결론적으로, 제2형당뇨병환자에서스타틴치료시 HDL 콜레스테롤은오히려그수치가감소하는환자들도있었다는것이관찰되었고, 향후이에대한연구가더필요할것으로생각된다. 요 목적 : 스타틴은심혈관계질환의일차및이차예방에효과적인것으로받아들이고있지만 HDL 콜레스테롤을올리는데있어서는개인간에편차가큰것으로알려져있다. 본연구는제 2형당뇨환자에서스타틴치료시 HDL 콜레스테롤의변화를살펴보기위해시행하였다. 방법 : 217명의제 2형당뇨와이상지혈증을가진환자를대상으로스타틴의반응을살펴보았다. 진료기록부를근거로한후향적연구로본연구를시행하였다. 피브린산유도체나니코틴산을병합하여사용하고있는환자나이전에스타틴을사용한환자, 크레아티닌이 1.5 mg/dl 이상, 공복중성지방이 300 mg/dl 이상인경우, 그리고만성간질환이있는경우는연구대상에서제외시켰다. 결과 : HDL 콜레스테롤은평균 2.3% 감소하였다. HDL 콜레스테롤의퍼센트변화에영향을준인자는기저 HDL 콜레스테롤, LDL 콜레스테롤의퍼센트변화, 총콜레스테롤, 기저총콜레스테롤이었다. 그중기저 HDL 콜레스테롤이퍼센트변화에가장강력한인자였다. 기저 HDL 콜레스테롤으로대상을 5분획으로나누어보면기저 HDL 콜레스테롤값이높을수록 HDL 콜레스테롤값은많이감소하였다. 결론 : 제2형당뇨병환자에서스타틴치료시 HDL 콜레스테롤변화는기대했던효과와달리오히려그수치가감소하는환자들도있었다는것이관찰되었고, 향후이에대한전향적인연구가더필요할것으로생각된다. 중심단어 : 스타틴 ; 고밀도콜레스테롤 ; 제 2 형당뇨병 약 REFERENCES 1) Scandanavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet 344: , ) Shepherd J, Ford I, Cobbe SM, Isles CG, Lorimer AR, MacFarlane PW, Mckillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with

7 - Jong-Ryul Park, et al : The effect of statins on HDL-cholesterol level - hypercholesterolaemia. N Engl J Med 333: , ) Sever PS, Poulter NR, Dahlof B, Wedel H, Collins R, Beevers G, Caulfield M, Kjeldsen SE, Kristinsson A, McInners GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes. Diabetes Care 28: , ) Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton- Menys V, Fuller JH. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet 364: , ) 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 285: , ) Gordon T, Castelli WP, Hjortland MC, Kannnel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. Am J Med 62: , ) Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA. High-density lipoprotein cholesterol and cardiovascular disease. Circulation 79:8-15, ) Bruckert E, Baccara-Dinet M, Eschwege E. Low HDLcholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan- European survey. Diabet Med 24: , ) Le Goff W, Guerin M, Chapman MJ. Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia. Pharmacol Ther 101:17-38, ) Schaefer JR, Schweer H, Ikewaki K, Stracke H, Seyberth HJ, Kaffarnik H, Maisch B, Steinmetz A. Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease. Atherosclerosis 144: , ) Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, prava- -statin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 81: , ) Streja L, Packard CJ, Shepherd J, Cobbe S, Ford I. Factors affecting low-density lipoprotein and high-density lipoprotein cholesterol response to pravastatin in the West of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol 90: , ) Chapman MJ. Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. Pharmacol Ther 111: , ) Kajinami K, Brousseau ME, lanon-fava S, Ordovas JM, Schaefer EJ. Gender-specific effects of estrogen receptor alpha gene haplotype on high-density lipoprotein cholesterol response to atrorvastatin: interaction with apolipoprotein AI gene polymorphism. Atherosclerosis 178: , ) Mahaney MC, Blangero J, Rainwater DL, Comuzzie AG, VandeBerg JL, Stern MP, MacCluer JW, Hixson JE. A major locus influencing plasma high-density lipoprotein cholesterol levels in the San Antonio Family Heart Study: segregation and linkage analyses. Arterioscler Thromb Vasc Biol 15: , ) Austin MA, Talmud PJ, Luong LA, Haddad L, Day IN, Newman B, Edwards KL, Krauss RM, Humphries SE. Candidate-gene studies of the atherogenic lipoprotein phenotype: a sib-pair linkage analysis of DZ women twins. Am J Hum Genet 62: , ) Knoblauch H, Bauerfeind A, Toliat MR, Becker C, Luganskaja T, Günther UP, Rohde K, Schuster H, Junghans C, Luft FC, Nürnberg P, Reich JG. Haplotypes and SNPs in 13 lipidrelevant genes explain most of the genetic variance in highdensity lipoprotein and low-density lipoprotein cholesterol. Hum Mol Genet 13: , ) Lahoz C, Pena R, Mostaza JM, Jimenez J, Subirats E, Pinto X, Taboada M, Lopez-Pastor A. Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy. Atherosclerosis 168: ,

Treatment and Role of Hormaonal Replaement Therapy

Treatment and Role of Hormaonal Replaement Therapy Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal