高脂血癥治療目標(biāo)高密度脂蛋白課件

1、Slide SourceLipidsOnlineSlide SourceLipidsOnline1001602200.01.02.03.0Risk of CHDHDL-C(mg/dL)LDL-C (mg/dL)25Gordon T et al. Am J Med 1977;62:707-714.456585Slide SourceLipidsOnlineExpert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.Low HDL-

2、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/dLSlide SourceLipidsOnlinenSmokenAre sedentarynAre obesenAre insulin resistant or diabeticnHave hypertriglyceridemianHave chronic inflammatory disordersLow HDL-C le

3、vels are commonly found in patients who:Slide SourceLipidsOnlineSlide SourceLipidsOnlinenReduced initiation and progression of atherosclerosis in transgenic mice and rabbitsnRegression of pre-existing atherosclerosis in animalsSlide SourceLipidsOnlinenIncrease apo A-I productionnPromote reverse chol

4、esterol transportnDelay catabolism of HDLSlide SourceLipidsOnlinenSmall molecule upregulation of apo A-I gene transcriptionnIntravenous infusion 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,

5、 intestine, muscle, hematopoetic cells)Slide SourceLipidsOnlinenIncrease apo A-I productionnPromote reverse cholesterol transportnDelay catabolism of HDLSlide SourceLipidsOnlineA-ICEFCFCFCSlide SourceLipidsOnlineFCFCoxysterolsABCA1A-ISlide SourceLipidsOnlineLXR/RXRNew agentsA-IFCABCA1Slide SourceLip

6、idsOnlinenIncrease apo A-I productionnPromote reverse cholesterol transportnDelay catabolism of HDLSlide SourceLipidsOnlinenAntioxidant effectsnInhibition of adhesion molecule expressionnInhibition of platelet activationnProstacyclin stabilizationnPromotion of NO productionSlide SourceLipidsOnlineCE

7、FCA-ISlide SourceLipidsOnlineSlide SourceLipidsOnlineCEFCA-IFCCETGSlide SourceLipidsOnlineCEFCA-ICETGXSlide SourceLipidsOnline05101520253035Okamoto H et al. Nature 2000;406:203-207.% Aortic Lesion ControlSimvastatinJTT-705Slide SourceLipidsOnlineCEFCA-IFCCETGXSlide SourceLipidsOnlinenWeight reductio

8、n and increased physical activitynLDL-C is primary target of therapynNon-HDL-C is secondary target of therapy (if triglycerides 200 mg/dL)nConsider nicotinic acid or fibratesExpert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.Slide Source

9、LipidsOnlinenTherapeutic lifestyle changesnSmoking cessationnRegular aerobic exercisenWeight lossnAlcohol use?Slide SourceLipidsOnlinenTherapeutic lifestyle changesnPharmacologic therapynStatinsSlide SourceLipidsOnline05101520253035Patients with Events (%)Scandinavian Simvastatin Survival Study Grou

10、p. Lancet 1995;345:1274-1275.HDL-C (mg/dL)PlaceboSimvastatin383944455253RR=0.67RR=0.71RR=0.57RR=0.70Slide SourceLipidsOnline024681012141618Patients with Events (%)LIPID Study Group. N Engl J Med 1998;339:1349-1357.HDL-CPlaceboPravastatin39 mg/dL37 mg/dL37 mg/dLP = 0.008P 0.001Slide SourceLipidsOnlin

11、e01020304050607080Events (%)Downs JR et al. JAMA 1998;279:1615-1622.HDL-C LevelsPlaceboLovastatin40 mg/dl404135Slide SourceLipidsOnlinenTherapeutic lifestyle changesnPharmacologic therapynStatinsnFibratesSlide SourceLipidsOnline0510152025Cumulative Incidence (%)0Rubins HB et al. N Engl J Med 1999;34

12、1:410-418.Copyright 1999, Massachusetts Medical Society. All rights reserved.123456YearPlaceboGemfibrozil22% reductionP = 0.006Slide SourceLipidsOnline050100150200050100150200303132333435050100150200TC (mg/dL)012345YearLDL-C (mg/dL)Year012345HDL-C (mg/dL)YearTG (mg/dL)Year012345PlaceboGemfibrozil4%,

13、 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 SourceLipidsOnlineVariable (Change)Risk Factor (95% CI)PDuring treatmentHDL

14、-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 SourceLipidsOnlinenTherapeutic lifestyle changesnPharmacologic therapynStatinsnFibratesnNiacinSlide

15、 SourceLipidsOnline-50-40-30-20-100102030Change 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 SourceLipidsOnlinenLifestyle changes and secondary causesnP

16、harmacologic therapynIf LDL-C elevated: statinnIf TG elevated: fibratenIf isolated low HDL-C: niacinnCombination therapySlide SourceLipidsOnline-30-20-100102030Change (%)Wolfe ML et al. Am J Cardiol 2001;87:476-479.Copyright 2001, Excerpta Medica Inc. Reprinted with permission.TCLDL-CHDL-CTGSlide So

17、urceLipidsOnlineCV Events0510152025Event 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 mg/dLTriple Therapy (n=75)19.818.81.3* p0.055.3*Slide SourceLipidsOnlinenLDL-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 leve