高脂血症治疗目标：密度脂蛋白

1、slide sourcelipidsoslide sourcelipidso1001602200.01.02.03.0risk of chdhdl-c(mg/dl)ldl-c (mg/dl)25gordon t et al. am j med 1977;62:707-714.456585slide sourcelipidsoexpert panel on detection, evaluation, and treatment of high b

2、lood 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/dlslide sourcelipidsonsmokenare sedentarynare obesenare insulin resistant or di

3、abeticnhave hypertriglyceridemianhave chronic inflammatory disorderslow hdl-c levels are commonly found in patients who:slide sourcelipidsoslide sourcelipidsonreduced initiation and progression of atherosclerosis in transgenic mice and rabbitsnregres

4、sion of pre-existing atherosclerosis in animalsslide sourcelipidsonincrease apo a-i productionnpromote reverse cholesterol transportndelay catabolism of hdlslide sourcelipidsonsmall 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 sourcelipidsonincrease apo a-i productionnpromote reverse cholesterol

6、transportndelay catabolism of hdlslide sourcelipidsoa-icefcfcfcslide sourcelipidsofcfcoxysterolsabca1a-islide sourcelipidsolxr/rxrnew agentsa-ifcabca1slide sourcelipidsonincrease apo a-i productionnpr

7、omote reverse cholesterol transportndelay catabolism of hdlslide sourcelipidsonantioxidant effectsninhibition of adhesion molecule expressionninhibition of platelet activationnprostacyclin stabilizationnpromotion of no productionslide sourcelipidsoce

8、fca-islide sourcelipidsoslide sourcelipidsocefca-ifccetgslide sourcelipidsocefca-icetgxslide sourcelipidso05101520253035okamoto h et al. nature 2000;406:203-207.% aortic lesion controlsimvastatinjtt-7

9、05slide sourcelipidsocefca-ifccetgxslide sourcelipidsonweight reduction 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

10、 panel on detection, evaluation, and treatment of high blood cholesterol in adults. jama 2001;285:2486-2497.slide sourcelipidsontherapeutic lifestyle changesnsmoking cessationnregular aerobic exercisenweight lossnalcohol use?slide sourcelipidsonthera

11、peutic lifestyle changesnpharmacologic therapynstatinsslide sourcelipidso05101520253035patients with events (%)scandinavian simvastatin survival study group. lancet 1995;345:1274-1275.hdl-c (mg/dl)placebosimvastatin383944455253rr=0.67rr=0.71rr=0.57rr=0.70slide sourcelipidson

12、024681012141618patients 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 sourcelipidso01020304050607080events (%)downs jr et al. jama 1998;279:1615-1622.hdl-c levels

13、placebolovastatin40 mg/dl404135slide sourcelipidsontherapeutic lifestyle changesnpharmacologic therapynstatinsnfibratesslide sourcelipidso0510152025cumulative incidence (%)0rubins hb et al. n engl j med 1999;341:410-418.copyright 1999, massachusetts

14、medical society. all rights reserved.123456yearplacebogemfibrozil22% reductionp = 0.006slide sourcelipidso050100150200050100150200303132333435050100150200tc (mg/dl)012345yearldl-c (mg/dl)year012345hdl-c (mg/dl)yeartg (mg/dl)year012345placebogemfibrozil4%, p0.001no changegemf

15、ibrozil & 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 sourcelipidsovariable (change)risk factor (95% ci)pduring treatmenthdl

16、-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 sourcelipidsontherapeutic lifestyle changesnpharmacologic therapynstatinsn

17、fibratesnniacinslide sourcelipidso-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 sourcelipidsonlinew

18、nlifestyle changes and secondary causesnpharmacologic therapynif ldl-c elevated: statinnif tg elevated: fibratenif isolated low hdl-c: niacinncombination therapyslide sourcelipidso-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 sourcelipidsocv 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/dll