1、Slide SourceLipidsOnlinewww.lipidsonline.org.Slide SourceLipidsOnlinewww.lipidsonline.org1001602200.01.02.03.0Risk of CHDHDL-C(mg/dL)LDL-C(mg/dL)25Gordon T et al.Am J Med 1977;62:707-714.456585.Slide SourceLipidsOnlinewww.lipidsonline.orgExpert Panel on Detection,Evaluation,and Treatment of High Blo
2、od Cholesterol in Adults.JAMA 2001;285:2486-2497.Low HDL-C was redefined as 102 cm(40 in)88 cm(35 in)TG150 mg/dLHDL-C Men Women40 mg/dL50 mg/dLBlood pressure130/85 mm HgFasting glucose110 mg/dL.Slide SourceLipidsOnlinewww.lipidsonline.orgnSmokenAre sedentarynAre obesenAre insulin resistant or diabet
3、icnHave hypertriglyceridemianHave chronic inflammatory disordersLow HDL-C levels are commonly found in patients who:.Slide SourceLipidsOnlinewww.lipidsonline.org.Slide SourceLipidsOnlinewww.lipidsonline.orgnReduced initiation and progression of atherosclerosis in transgenic mice and rabbitsnRegressi
4、on of pre-existing atherosclerosis in animals.Slide SourceLipidsOnlinewww.lipidsonline.orgnIncrease apo A-I productionnPromote reverse cholesterol transportnDelay catabolism of HDL.Slide SourceLipidsOnlinewww.lipidsonline.orgnSmall molecule upregulation of apo A-I gene transcriptionnIntravenous infu
5、sion of recombinant protein(wild-type apo A-I,apo A-IMilano)nAdministration of peptides based on apo A-I sequencenSomatic gene transfer of apo A-I DNA(liver,intestine,muscle,hematopoetic cells).Slide SourceLipidsOnlinewww.lipidsonline.orgnIncrease apo A-I productionnPromote reverse cholesterol trans
6、portnDelay catabolism of HDL.Slide SourceLipidsOnlinewww.lipidsonline.orgA-ICEFCFCFC.Slide SourceLipidsOnlinewww.lipidsonline.orgFCFCoxysterolsABCA1A-I.Slide SourceLipidsOnlinewww.lipidsonline.orgLXR/RXRNew agentsA-IFCABCA1.Slide SourceLipidsOnlinewww.lipidsonline.orgnIncrease apo A-I productionnPro
7、mote reverse cholesterol transportnDelay catabolism of HDL.Slide SourceLipidsOnlinewww.lipidsonline.orgnAntioxidant effectsnInhibition of adhesion molecule expressionnInhibition of platelet activationnProstacyclin stabilizationnPromotion of NO production.Slide SourceLipidsOnlinewww.lipidsonline.orgC
8、EFCA-I05101520253035.Slide SourceLipidsOnlinewww.lipidsonline.org05101520253035.Slide SourceLipidsOnlinewww.lipidsonline.orgCEFCA-IFC05101520253035CETG.Slide SourceLipidsOnlinewww.lipidsonline.orgCEFCA-ICETGX.Slide SourceLipidsOnlinewww.lipidsonline.org024681012141618Okamoto H et al.Nature 2000;406:
9、203-207.%Aortic Lesion ControlSimvastatinJTT-705.Slide SourceLipidsOnlinewww.lipidsonline.orgCEFCA-IFCCETGX.Slide SourceLipidsOnlinewww.lipidsonline.orgnWeight reduction and increased physical activitynLDL-C is primary target of therapynNon-HDL-C is secondary target of therapy(if triglycerides 200 m
10、g/dL)nConsider nicotinic acid or fibratesExpert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.JAMA 2001;285:2486-2497.Slide SourceLipidsOnlinewww.lipidsonline.orgnTherapeutic lifestyle changesnSmoking cessationnRegular aerobic exercisenWeight lossnAlcohol use?.Slide
11、 SourceLipidsOnlinewww.lipidsonline.orgnTherapeutic lifestyle changesnPharmacologic therapynStatins.Slide SourceLipidsOnlinewww.lipidsonline.org051015202530Patients with Events(%)Scandinavian Simvastatin Survival Study Group.Lancet 1995;345:1274-1275.HDL-C(mg/dL)PlaceboSimvastatin383944455253RR=0.67
12、RR=0.71RR=0.57RR=0.70.Slide SourceLipidsOnlinewww.lipidsonline.org01020304050607080Patients with Events(%)LIPID Study Group.N Engl J Med 1998;339:1349-1357.HDL-CPlaceboPravastatin39 mg/dL37 mg/dL37 mg/dLP=0.008P 0.001.Slide SourceLipidsOnlinewww.lipidsonline.org050100150200Events(%)Downs JR et al.JA
13、MA 1998;279:1615-1622.HDL-C LevelsPlaceboLovastatin40 mg/dl404135.Slide SourceLipidsOnlinewww.lipidsonline.orgnTherapeutic lifestyle changesnPharmacologic therapynStatinsnFibrates.Slide SourceLipidsOnlinewww.lipidsonline.org303132333435Cumulative Incidence(%)0Rubins HB et al.N Engl J Med 1999;341:41
14、0-418.Copyright 1999,Massachusetts Medical Society.All rights reserved.123456YearPlaceboGemfibrozil22%reductionP=0.006.Slide SourceLipidsOnlinewww.lipidsonline.org050100150200050100150200-50-40-30-20-100102030-30-20-100102030TC(mg/dL)012345YearLDL-C(mg/dL)Year012345HDL-C(mg/dL)YearTG(mg/dL)Year01234
15、5PlaceboGemfibrozil4%,P0.001No changeGemfibrozil&PlaceboPlaceboGemfibrozil+6%,P0.001012345PlaceboGemfibrozil31%,P0.001Rubins HB et al.N Engl J Med 1999;341:410-418.Copyright 1999,Massachusetts Medical Society.All rights reserved.Slide SourceLipidsOnlinewww.lipidsonline.orgVariable(Change)Risk Factor
16、(95%CI)PDuring treatmentHDL-C(5.0 mg/dL)0.89(0.810.98).02Triglycerides(50 mg/dL)1.03(0.951.11).48LDL-C(25 mg/dL)1.09(0.981.21).13Robins SJ et al.JAMA 2001;285:1585-1591.Copyright 2001,American Medical Association.Slide SourceLipidsOnlinewww.lipidsonline.orgnTherapeutic lifestyle changesnPharmacologi
17、c therapynStatinsnFibratesnNiacin.Slide SourceLipidsOnlinewww.lipidsonline.org0510152025Change from Baseline2500 mg3000 mgGoldberg A et al.Am J Cardiol 2000;85:1100-1105.2000 mg1500 mg1000 mg500mgHDL-CLDL-CLp(a)TG9%14%22%21%17%29.5%30%26%22%15%10%28%35%44%39%11%5%26%3%12%30%24%17%.Slide SourceLipids
18、Onlinewww.lipidsonline.orgnLifestyle changes and secondary causesnPharmacologic therapynIf LDL-C elevated:statinnIf TG elevated:fibratenIf isolated low HDL-C:niacinnCombination therapy.Slide SourceLipidsOnlinewww.lipidsonline.orgNoImageChange(%)Wolfe ML et al.Am J Cardiol 2001;87:476-479.Copyright 2
19、001,Excerpta Medica Inc.Reprinted with permission.TCLDL-CHDL-CTG.Slide SourceLipidsOnlinewww.lipidsonline.orgCV EventsNoImageEvent Rate(%)Brown BG et al.Circulation 1998;98:I-635.Usual Care(n=101)DeathsLDL-C 188166 mg/dL;HDL-C 3840 mg/dL;TG 208220 mg/dLLDL-C 202106 mg/dL;HDL-C 4353 mg/dL;TG 210134 m
20、g/dLTriple Therapy(n=75)19.818.81.3*p0.055.3*.Slide SourceLipidsOnlinewww.lipidsonline.orgnLDL-C remains the primary target of lipid-altering therapiesnHDL-C is an important CHD risk factornEven small increases in HDL-C may confer substantial benefitnIntervention to raise HDL-C levels should be considered in high-risk patients.Slide SourceLipidsOnlinewww.lipidsonline.orgn48-year-old man with metabolic syndrome and CHDnAfter therapeutic lifestyle changes and a starting dose of statin:Cholesterol 179 mg/dL Triglycerides 252 mg/dL LDL-C 97 mg/dL HDL-C 32 mg/dL Glucose 104 mg/dL.
