高甘油三酯血症的治疗目标与措施课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,高甘油三酯血症的治疗目标与措施,（优选）高甘油三酯血症的治疗目标与措施,Overall Risk Reduction for Major Coronary Events by Age:A Meta-analysis,LaRosa JC,et al.,JAMA.,1999;282:2340-2346.,No.of EventsRRR,%ARR/1000,NNT,P,65 y,74053932(23 to 39),44(30 to 58)0.001,4S16812238(19 to 53)98(43 to 154),23,0.001,CARE1116942(20 to 57)65(27 to 103),(17-33),0.001,LIPID34927025(11 to 37)42(17 to 67)0.001,AFCAPS1127832(8 to 49)21(5 to 38)0.01,65 y130295131(24 to 36)32(24 to 40)0.001,4S45430938(27 to 47)83(55 to 110)0.001,CARE16314314(-9 to 32)14(-8 to 37),31,0.21,LIPID36628725(12 to 37)31(13 to 48),(25-41),0.001,WOSCOPS24817431(16 to 44)23(11 to 34)0.001,AFCAPS713847(22 to 63)19(8 to 31)0.001,PI,Statin,(95%CI),(95%CI),(95%CI),Value,他汀类药物显著降低心血管死亡率与全因死亡率,LaRosa JC,et al.,JAMA.,1999;282:2340-2346.,血脂不是动脉粥样硬化性疾病唯一的危险因素,胆固醇不是血脂谱中唯一的有害成分,他汀不是唯一的调脂药物,为全面控制心血管危险，仅仅他汀降胆固醇是不够的,0.0,0.5,1.0,1.5,2.0,2.5,3.0,50,100,150,200,250,300,350,400,Men,Women,RR,TG(mg/dL),Castelli WP.,Can J Cardiol,.1988;4:5A-10A.,Impact of TG Levels on Relative Risk of CHD:Framingham Heart Study,SHEEP:Risk Factors for Nonfatal MI in Men and Women,SHEEP=Stockholm Heart Epidemiology Program.,Reuterwall C et al.,J Intern Med,.1999;246:161-174.,Risk FactorDiabetes,High TC,(,6.5 mmol/L)High TG(6.3 mmol/L)HTN(170/95 mm Hg)Overweight(BMI 30 kg/m)WHR(0.85)Physical inactivitySmokingJob strain,Men,Women,0,1,2,3,4,5,6,7,8,Odds Ratio,Events/,1,000 in 8 yr,Assmann G et al.,Am J Cardiol.,1992;70:733-737.,TG(mg/dL),44,93,132,81,0,50,100,150,220,220,220,TG,123 mg/dL TG,123 mg/dL,Fasting TG and Risk for CHD Death:Paris Prospective Study,最新荟萃分析表明,冠脉事件危险性随甘油三酯水平增高而增高,甘油三酯水平是冠心病独立危险因素,在重点关注胆固醇的同时,亦应关注甘油三酯,甘油三酯水平的分类,甘油三酯分类,ATP III,标准,正常,5.65mmol/L),：其主要治疗目的是尽快降低甘油三酯水平，预防发生急性胰腺炎。可首选贝特类或烟酸类调脂药物。,如何选用合适的降脂药物？,他汀类,贝特类,烟酸类,胆酸螯合剂,胆固醇吸收抑制剂,调脂药物治疗的疗效比较,分类,TC,LDL,C,TG,HDL,C,（,%,）,他 汀类,20-40,20-60,7-30,5-10,贝特类,5,-20,5-20,20-50,10-20,烟酸类,树脂类,5-25,5-25,15-30,20-50,20-30,3-5,贝特类的作用机理,贝特类,胆固醇,逆向转运,LDL,颗粒大小,HDL,合成,炎症,甘油三酯,PPAR a,p,-,值,一级预防,总人群,:,总人群,:,总人群,:,0.26,9.4,13.6,15.0,3,090,BIP,2,5,LDL/HDL,5,甘油三酯值以,mg/dl,为单位（,204 mg/dl,2.3 mmol/L,）,HHS:,TG,和,LDL,HDL,比率高的患者,CHD,事件率下降显著,减少,71,%,p,0.005,严重,CVD,事件率,(%),p,-,值,对照,RRR(%),药物,n,试验,一级预防,总人群,:,总人群,:,总人群,:,0.26,9.4,13.6,15.0,3,090,BIP,2,0.02,34,27.3,41.4,4,081,0.006,21.7,22,17.3,2,531,VA-HIT,3,二级预防,HHS,1,1.Frick MH et al.N Engl J Med 1987;317:123745,2.The BIP Study Group.Circulation 2000;102:217,3.Rubins HB et al.N Engl J Med 1999;341:4108,贝特类试验结果,BIP=,苯扎贝特梗死预防研究；,HHS=,赫尔辛基心脏研究；,RRR=,相对危险降低；,VA-HIT=,美国退伍军人高密度脂蛋白胆固醇干预研究。,0,1,2,3,4,5,6,20,16,12,8,4,0,率(%),甘油三酯 200,mg/dl,甘油三酯,200,mg/dl,安慰剂,苯扎贝特,p,=0.02,基线,LDL-,胆固醇:安慰剂 148,mg/dl(3.8 mmol/L);,苯扎贝特,149 mg/dl,降低,39.5%,BIP:,在甘油三酯基线,200mg/dl,患者中事件率的下降显著,The BIP Study Group.Circulation 2000;102:217,0,1,2,3,4,5,6,20,16,12,8,4,0,安慰剂,苯扎贝特,p,=0.86,时间(年,),率(%),时间(年,),FIELD,研究,Total cholesterol,：,11%reduction,LDL cholesterol:12%reduction,Triglyceride:29%reduction,HDL cholesterol:NS,FIELD,研究结果,结果,相对风险下降*,(95%CI),p-,值,主要终点,(,CHD,事件),未调整,11%(-5到,25),0.16,调整他汀类使用*,19%(4,到 32),0.01,次要终点,(总,CVD,事件),未调整,11%(1,到,20),0.035,调整他汀类使用,*,15%(5,到,24),0.004,*,非诺贝特与安慰剂比较,*,非随机比较调整研究中的他汀类使用,FIELD Study Investigators.Lancet 2005;366(9500):1849-61,需要激光治疗视网膜病变,“,在非诺贝特组这一作用无法用,HbA,1c,的变化或合并用药或血压的轻度降低解释,”,P=0.0003,-30,%,FIELD,研究结果：微血管疾病视网膜病变,FIELD Study Investigators.Lancet 2005;366(9500):1849-61,FIELD,研究结果：,微量蛋白尿的进展,(,基线到研究结束,),缓解,无变化,进展,安慰剂,(n=4900),400,(8.2%),3654,(74.6%),539,(11.0%),非诺贝特,(n=4895),462,(9.4%),3583,(73.2%),466,(9.5%),Mann-Whitney,检验,:,P,=0.002,蛋白尿情况分类,:,正常,:3.5 mg/mmol;,微量蛋白尿,:3.5-,35 mg/mol,“,非诺贝特,组的这一结果无法用,HbA,1c,变化或合并用药或用血压轻度降低解释,”,FIELD Study Investigators.Lancet 2005;366(9500):1849-61,剂量及用法,吉非贝齐每日,0.91.2g,分,23,次服用,非诺贝特一般,0.1g/,次,3/d,有效后,0.1g/,次,2,次,/d,微粒化非诺贝特,0.2/,次,1,次,/d,苯扎贝特,0.2g/,次，2-,3,次,/d,常用调脂药物,贝特类,常用调脂药物,贝特类,不良反应,-,胃部不适、恶心、食欲不振,-,血清转氨酶升高,-,伴血清,CK,增高的肌炎样疼痛（偶有）,烟酸的作用机制,肝脏,循环,HDL,血清,VLDL,使,LDL,分解减少,血清,LDL-C,VLDL,肝脏产生,VLDL,和,apo B,减少,VLDL,分泌,Apo B,肝细胞,全身循环,动员,FFA,TG,合成,VLDL,LDL,CDP,研究结果,ARBITER-2,研究,ARBITER-2,研究,Circulation,，,Volume 110(23),7 December 2004,pp 3512-3517,常用调脂药物,烟酸类,剂量及用法,-,缓释烟酸开始,0.5g/,晚，5-8周增至1.0,g/,晚，,以后根据反应调整剂量至1.52.0,g/,晚。,-,阿西莫司,0.25g/,次，,23,次,/d,，饭后服用,不良反应,常见副反应：,面部潮红、皮肤血管扩张,消化不良、胃肠胀气、腹痛和腹泻等,严重的副反应：,消化性溃疡,糖耐量降低,糖尿病恶化,增高血尿酸，甚至引起痛风,阿西莫司无初效反应，可改善葡萄糖耐受性，不引起尿酸代谢变化,常用调脂药物,烟酸类,食物胆固醇,胆系排泄,INTESTINE,排泄,VLDL,LDL,LDL-R,胆固醇吸收抑制剂依折麦布,Synthesis,IDL,吸收,胆固醇吸收抑制剂,依折麦布,19%,50%,50%,31%,50%,依折麦布（,Ezetimibe),唯一的胆固醇吸收抑制剂,单药治疗,(10mg/d)LDL-C,约降低,18%,与他汀类合用对,LDL-C,HDL-C,和,TG,的作用进,一步增强,未见有临床意义的药物间药代动力学的相互,作用,安全、耐受性良好,Effect of Ezetimibe Monotherapy on Lipids in Patients With Primary Hypercholesterolemia,Dujovne CA et al.,Am J Cardiol.,2002;90:1092-1097.,-1.6,-16.9*,-5.7*,+5.7,+0.4,+1.3*,-20,-15,-10,-5,0,5,10,LDL-C,TG,HDL-C,Placebo(n=226),Ezetimibe 10 mg(n=666),*,P,0.01.,Mean%,D,from baseline,www.lipidhealth.org,联合用药基本概念,目的：减小剂量，降低毒性，增强疗效,（协同作用）,对