1、Parametermg/dLNormal TG 1,000Low HDL-C 35High(protective)HDL-C 60Expert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.JAMA 1993;269:30153023Niacin 1535%Fibrates 1015%Estrogens 1015%Statins 510%Belalcazar LM et al.Progr Cardiovasc Dis 1998;41:151174LiverBBTGCMR/IDLC-
2、IICM/VLDLLPLA-ICECEFCFCLCATA-IABC1MacrophageMature HDLNascent HDLLDLRHLIntestineNIACINNIACIN*Inhibits uptake of apoA-I but not CE*Significant difference(P 0.001)between dosage groups.1.Morgan JM et al.Am J Cardiol 1998;82(12A):29U34U2.Capuzzi DM et al.Am J Cardiol 1998;82(12A):74U81U Copyright 1998,
3、with permission from Excerpta Medica Inc.%change from baselineBaseline(mg/dL):-617-1523-28-2028-40-30-20-10010203040TG(156)LDL-C(197)HDL-C(44)TG(137)LDL-C(206)HDL-C(42)TG(174)LDL-C(195)HDL-C(45)1,000 mg/d*(1)(12 wk;n=35)2,000 mg/d*(1)(12 wk;n=31)3,000 mg/d(2)(96 wk;n=225)-21-28ClCOOCH3CH3CCOOCHCH3CH
4、3ClFenofibrateClofibrateOCCOOC2H5CH3CH3CCOOHCH3CH3CH2OCH2CH2CH2CH3CH3GemfibrozilLiverBBTGCMR/IDLC-IICM/VLDLLPLA-ICECEFCFCLCATA-IABC1MacrophageMature HDLNascent HDLLDLRHLFIBRATES+FIBRATESIntestine*Mean percentage changes,not percentage changes in means.Goldberg AC et al.Clin Ther 1989;11:6983.14.519.
5、6-46.245.022.9-54.5-60-50-40-30-20-1001020304050Group A(TG=350499 mg/dL)Group B(TG=5001,500 mg/dL)%change from baseline*LDL-C(128.4)HDL-C(33.7)LDL-C(103.1)HDL-C(29.6)Mean baseline(mg/dL):Total-TG(432.0)Total-TG(725.6)1.Vega GL,Grundy SM.JAMA 1989;262:314831532.Miller M et al.Am J Med 1993;94:7123.La
6、vie CJ et al.Am J Cardiol 1992;69:108310854.King JM et al.Am J Med 1994;97:3233315.Miller M et al.Arterioscler Thromb Vasc Biol 1995;15:215121569927311205101520253035Vega(1)(n=22)Miller(2)(n=14)Lavie(3)(n=19)King(4)(n=15)Miller(5)(n=39)GemfibrozilNiacinPhenytoin%increase in HDL-CTrial:LiverBBTGCMR/I
7、DLC-IICM/VLDLLPLA-ICECEFCFCLCATA-IABC1MacrophageMature HDLNascent HDLLDLRHLESTROGENS+ESTROGENSIntestineCEE=conjugated equine estrogen;MPA=medroxyprogesterone acetate;cyc=cyclic administration(days 1 through 12 of each month);con=administered daily for 1 month;MP=micronized progesteroneWriting Group
8、for PEPI Trial.JAMA 1995;273:199208-2.9-2.0-3.2-10.39.013.9-12.92.413.5-11.61.911.1-10.96.513.7-20-15-10-505101520LDL-CHDL-CTGPlaceboCEECEE+MPA(cyc)CEE+MPA(con)CEE+MP(cyc)(143.3)(140.6)(137.0)(141.7)(135.7)%change from baseline(61.4)(61.9)(64.8)(62.7)(62.6)(99.0)(98.7)(94.3)(102.7)(97.5)Baseline(mg/
9、dL):OHCH3CH3H3CH3COHOSimvastatinH3CHOOOHCH3HH3CHOOHHOPravastatinCOONaHHH3COOHCH3HH3CH3CHOLovastatinHH3CHNO*Na+CH3CH3FluvastatinCerivastatinNHCNNHCCH3OCH2CH3Naphthalene sub-class(hydronaphthalene ring in common)Fluorophenyl sub-class(fluorophenyl ring in common)*The clinical impact of these differenc
10、es is not known.Lennernas H et al.Clin Pharmacokinet 1997;32:403423.AtorvastatinOCH3CH3OHOHOOOOOOHOHCH3CH3FFOFOHOHOCH3FOHOHO*Na+OCH3CH3NO*Ca+O*NLiverBBTGCMR/IDLC-IICM/VLDLLPLA-ICECEFCFCLCATA-IABC1MacrophageMature HDLNascent HDLLDLRHL+STATINSIntestineSTATINSSTATINS+?nMean age(range):53 y(2170 y)nSex(
11、M/F):68/62(N=130)nBaseline lipids:nLDL-C(mean)156 mg/dLnHDL-C(mean)39 mg/dLnTG(median)389 mg/dLnType-2 diabetes mellitus:n=21(16%)Stein E et al.Am J Cardiol 2000;86:406-411 PlaceboSimvastatin 40 mgSimvastatin 80 mg*Mean;mediann=119121 per treatment groupP 0.05 for between-treatment comparisonsStein
12、E et al.Am J Cardiol 2000;86:406-41123-4-2913-28-3616-33-50-40-30-20-1001020LDL-C*HDL-C*TG%changePlaceboSimvastatin 40 mgSimvastatin 80 mgn=120123 per treatment groupaS40 vs placebo:P 0.001;bS80 vs placebo:P 0.001;cS40 vs S80:P 0.05;dS40 vs placebo:P 0.005 Stein E et al.Am J Cardiol 2000;86:406-4114
13、435-23889-31111211-35-30-25-20-15-10-5051015ApoBa,b,cApoA-Ib,dLpA-Ib,dLpA-I:A-IIb,dMean%changenOpen-label,randomized,parallel,12-week studyn842 patients(42%female)nTreatments:nSimvastatin 40 mg and 80 mgnAtorvastatin 20 mg and 40 mgnLDL-C inclusion criteria:nCHD:130 mg/dLnNo CHD plus 2 risk factors:
14、160 mg/dLnNo CHD plus 2 risk factors:190 mg/dLnTG 350 mg/dLCrouse JR III et al.Am J Cardiol 1999;83:14761477Simvastatin 40 mg(n=202)Atorvastatin 20 mg(n=210)Simvastatin 80 mg(n=215)Atorvastatin 40 mg(n=215)*Mean;medianCrouse JR III et al.Am J Cardiol 1999;83:14761477-60-50-40-30-20-100P=0.04P=0.10NS
15、P 0.01LDL-C*TG%change-42.7-45.0-49.2-51.1-23.0-23.3-25.2-29.6Simvastatin 40 mgAtorvastatin 20 mgSimvastatin 80 mg Atorvastatin 40 mgMean%changeP 0.01 P 0.001NS*N=842;N=113Crouse JR III et al.Am J Cardiol 1999;83:14761477024681012141618HDL-CApoA-IHDL-C 35 mg/dLP 0.001NSP=0.002All patients*Subgroup an
16、alysis6.74.06.63.06.35.05.90Kastelein JJP et al.Am J Cardiol 2000;86:221-223.Copyright 2000,with permission from Excerpta Medica Inc.024681012%Change from BaselineWeeks6126128.57.39.76.45.64.05.71.0*Simvastatin 40 mgAtorvastatin 20 mgSimvastatin 80 mgAtorvastatin 40 mgTG 177 mg/dLTG 177 mg/dL0246810
17、1214Placebon-3 fatty acidsP 0.008NSHarris WS.Lipids 1996;31:243252HDL-C net change(%)from baseline1.Guyton JR,Capuzzi DM.Am J Cardiol 1998;82:82U84U2.Jacobson TA et al.Am J Cardiol 1994;74:149154-3931-36-4028-30-50-40-30-20-10010203040LDL-CHDL-CTGLDL-CHDL-CTGSimvastatin+Niacin(1)Fluvastatin+Niacin(2
18、)Mean%change from baseline1.Wierzbicki AS et al.QJM 1997;90:6316342.Wiklund O et al.Am J Med 1993;94:1320Mean%change from baseline-4120-17-3717-42-50-40-30-20-100102030LDL-CHDL-CTGLDL-CHDL-CTGSimvastatin+Fenofibrate(1)Pravastatin+Gemfibrozil(2)Brown BG et al.Am J Cardiol 1997;80:111115-60.413-32.4-5
19、4.421.7-38.7-5.52.13.6-70-60-50-40-30-20-100102030LDL-C(215)HDL-C(46)TG(191)Baseline(mg/dL):Controlled-release niacin+lovastatin+colestipol(8 mos)Regular niacin+lovastatin+colestipol(8 mos)No therapy(6 wks)Change in lipid levels(%)Prosn Better TG and HDL-Cn May LDL-C more(niacin or fenofibrate)n Lp(
20、a)(niacin)n LDL particle sizen Fibrinogen(fibrates)n Angiographic dataConsn Increased cost and complexityn Increased myositis riskn Increased hepatitis risk(niacin)n Potential for other drug interactionsn Lack of outcome datanPharmacologic agents have different effects on HDL metabolism that lead to
21、 increased HDL-C levels.nTherapy with niacin leads to the greatest increase in HDL-C levels;both efficacy and toxicity are dose related.nStatins can increase HDL-C levels more than previously recognized.nCombination therapy with the addition of niacin or a fibrate to a statin is very effective for improving the lipid pro increases the cost and risk of therapy.谢谢您的聆听与观看THANK YOU FOR YOUR GUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。欢迎下载！汇报人：XXX日期：20XX年XX月XX日
