脂代谢与动脉粥样硬化

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1、脂代谢与动脉粥样硬化抗动脉粥样硬化新途径－－双重抑制胆固醇的吸收与合成华中科技大学协和医院心内科廖玉华ElevatedCholesterolIsaRiskFactorforCVDElevatedserumcholesterolisassociatedwithincreasedriskofCHDReinfarctionCVDmortalityAll-causeCHDStrokeCVD=cardiovasculardisease*Crudedeathrate(per10,000person-years)Adapte

2、dfromKannelWB.AmJCardiol.1995;76:69C–77C;AndersonKM,etal.JAMA.1987;257:2176–2180;KannelWB,etal.AnnInternMed.1971;74:1–12;NeatonJD,etal.ArchInternMed.1992;152:1490–1500.01020304050<160160–199200–239240CVDMortalityRate*MultipleRiskFactorInterventionTrial(N=350,9

3、77)SerumCholesterol,mg/dLRelationshipBetweenLDL-CandCHDRiskinClinicalTrialsHPS=HeartProtectionStudy;CARE=CholesterolAndRecurrentEventsTrial;LIPID=Long-termInterventionwithPravastatininIschaemicDisease;4S=ScandinavianSimvastatinSurvivalStudy;TNT=TreatingtoNewTa

4、rgets*EventratesforHPS,CARE,andLIPIDarefordeathfromCHDandnonfatalmyocardialinfarction(MI).Eventratesfor4SandtheTNTstudyalsoincluderesuscitationaftercardiacarrest.AdaptedfromLaRosaJC,etal.NEnglJMed.2005;352:1425–1435.LDL-C,mg/dLEvent*,%0300110170210252015105130

5、701501904S4SCAREHPSTNT(atorvastatin80mg)90LIPIDStatinPlaceboTNT(atorvastatin10mg)HPSCARELIPID人类胆固醇净平衡肠道合成胆固醇（800mg/天）胆汁胆固醇／胆汁酸粪固醇（1100mg/天）肝外组织肝脏食物胆固醇（300mg/天）乙酰辅酶A胆固醇胆固醇INHIBITIONOFCHOLESTEROLSYNTHESISRESULTSINAHIGHERABSORPTIONRATEOFCHOLESTEROLFROMTHEINTESTIN

6、E*AssmannG,etal.JAmCollCardiol2004;43(5,Suppl.2):A445-A446;GoldbergAC,etal.MayoClinProc.2004May;79(5):620-9.InhibitionofcholesterolsynthesisLDL-C31-46%synthesisabsorption(simvastatin10-80mg)FoodCholesterolexcretedinthefaecesHEPATICBIOSYNTHESISINTESTINALABSORPTI

7、ON30-50%absorption*Measuredastheratioofserumlevelsofcholesterolabsorptionmarker(sitosterol)andtotalcholesterol.STATINS胆固醇合成标志物下降与胆固醇吸收标志物升高相关阿托伐他汀降低了胆固醇的合成，但增加了胆固醇的吸收Lamon-FavaSetal.JLipidRes.2007;48:1746–1753.在一项为期8周交叉研究中，9名高胆固醇血症患者接受阿伐他汀治疗菜油甾醇(胆固醇吸收标志物)(n=9)7

8、-烯胆甾烷醇(胆固醇合成标志物)(n=9)阿伐他汀vs安慰剂的变化%*P<0.005vs安慰剂**4871**-69-76–100–80–60–40–20020406080100阿伐他汀20mg/日阿伐他汀80mg/日THEINHIBITIONOFCHOLESTEROLABSORPTIONRESULTSININCREASEDCHOLESTERO