降脂与动脉粥样硬化斑块的逆转

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,*,降脂与动脉粥样硬化斑块的逆转,来自辛伐他汀的研究证据,泡沫,细胞,脂质,条纹,中间阶,段损伤,动脉粥样化,纤维,斑块,复合病变破裂,从十几岁开始,从,30,岁开始,从,40,岁开始,主要为脂肪积聚,平滑肌细胞和胶原,栓塞,出血,内皮功能不全,Modified from Pepine,CJ,Am J Card,1998,动脉粥样硬化,慢性进展性的疾病,稳定心绞痛心肌梗死,缺血性中风,/TIA,间歇性跛行,CV,死亡,Atherosclerosis,稳定性心绞痛,/,间歇性跛行,动脉粥样硬化,慢性进展性的疾病,血栓形成,Adapted from,Libby P.,Circulation.,2001;104:365-372.,冠状动脉内粥样斑块,“,稳定”斑块,“,易损”斑块,心肌缺血,劳力性心绞痛，,CHF,等,堵塞管腔,斑块破裂,管腔急性狭窄,或闭塞,ACS,(SCD,AMI,UAP),不稳定性斑块与稳定性斑块,薄的纤维帽,炎性细胞,少的平滑,肌细胞,内皮细胞不完整,巨噬细胞,较厚的纤维帽,没有炎性细胞,泡沫细胞,完整的内,皮细胞,较多平滑,肌细胞,Libby P.,Circulation,.1995;91:2844-2850.,不稳定,稳定,斑块狭窄程度与冠脉事件的危险性,None,5-49%50-80%81-95%,%Occlusion at 5 Years,Stenosis,Severity at Baseline,0,5,10,15,20,25,Angio,2.0-2.9,(n=17),3.0-3.9,(n=36),4.0-4.9,(n=55),5,(n=193),Minimum Luminal CSA mm),Any Cardiac Event(%),IVUS,多数心肌梗死由轻度狭窄斑块引起,Pooled data from 4 studies:Ambrose et al,1988;Little et al,1988;Nobuyoshi et al,1991;and Giroud et al,1992.(Adapted from Falk et al.),Falk E et al,Circulation,1995.,Angiographic and,angioscopic,images of a 58-year-old man with anterior myocardial infarction,Multiple“vulnerable”,plaques detected in,nonculprit,segments 10-12,Culprit lesion(#8),detected with,thrombus(red),Multiple“vulnerable”,plaques detected in,nonculprit,segments 1-7,多数急性冠脉综合症存在多发性不稳定斑块,Reprinted with permission from,Asakura,M,et al.,J Am,Coll,Cardiol,.,2001;37:1284-1288.,ACS:,冰山之角,Adapted from,Goldstein JA.,J Am,Coll,Cardiol,.,2002;39,:,1464-1467.,Presence of Multiple,Coronary Plaques,多个病变,Vascular,Inflammation,血管炎症,Persistent,Hyperreactive,Platelets,持续的血小板过度反应,Clinical,Subclinical,Acute Plaque Rupture ACS(UA/NSTEMI/STEMI),动脉粥样硬化斑块的发生和发展,细胞黏附分子表达增加,炎性细胞进入内皮下,泡沫细胞形成,内皮损伤,巨噬细胞吞噬氧化,LDL,脂纹，脂质斑块形成,单核细胞和,T,淋巴细胞趋化,他汀,*,LDL-C,下降,乳糜微粒和,VLDL,残余,IDL,LDL-C,的下降,恢复内皮功能,维护平滑肌细胞,抗炎作用,减少血栓形成,内腔,脂质核心,巨噬细胞,平滑肌细胞,ACS,患者他汀治疗获益的原理,相对危险性下降,RIKS-HIA-Cox,回归分析他汀及,/,或,14,天内进行血管再通术比较,心梗后的死亡率,(14-365,天，,n=19,305),400,400,300,300,200,200,100,100,0,0,Cumulative probability of death,Cumulative probability of death,.05,.05,.04,.04,.03,.03,.02,.02,.01,.01,0.00,0.00,None(12,313),只有他汀治疗*,(4,707),14天内进行血管再通术,(1,525),14,天内进行血管再通术+,他汀治疗*(,760),34%,(p0.001),46%,(p0.001),64%,(p 190(5.0),LDL 115(3.0),冠脉病变,50%,44,男性,辛伐他汀,40 mg,治疗,12,个月,(2,例未达标增至,80mg/d),，,LDL-C,降低近,46.3%,主要终点,:,冠脉内超声检测斑块体积的变化,12,个月,Jensen LO,et al.Circulation,2004;110:265-270,饮食,3,个月,辛伐他汀治疗逆转冠状动脉粥样硬化,-IVUS,研究,辛伐他汀减少动脉粥样硬化斑块体积（,IVUS,测定）,冠脉,斑块,体积,(mm,3,),辛伐他汀,40 mg,12,个月,基线,饮食,3,个月,50,40,30,6.3,*,p100 mg/,dL,LDL-C,100 mg/,dL,LDL-C,100 mg/,dL,LDL-C,100 mg/,dL,n=19,n=34,n=24,n=11,p=0.027,p=0.36,Aorta,Carotid,%Change in Vessel Wall Area,Corti,et al.,JACC 46:106-12,2005,MRI,粥样硬化病变治疗策略,血管重建,+,他汀,他汀,严重狭窄病变,无严重狭窄病变,4S,研究的重大贡献,第一个他汀治疗冠心病的大型临床研究,首次证实辛伐他汀,20-40mg/,天降低,LDL-C,达,35%,，降低冠心病的总死亡率达,30%,与以前的临床研究不同，HPS 是一个同时包括一级及二级预防的大型的、长期的前瞻性研究,急性冠脉事件,4,S,3,4,个月,没有,CAD,病史,不稳定,CAD,3,个月,t=0,6,个月,Randomization:6 mo,一级预防,二级预防,心脏保护研究,4,心脏保护研究,(HPS)-,稳定,CAD,MIRACL,AFCAPS/TexCAPS/WOSCOPS,Duration of follow-up:,1,5.0 years;,2,6.1 years;,3,5.4 years;,4,XXyears,.,Randomization:2496 h,CARE,1,/LIPID,2,Randomization:CARE-320 moLIPID-336 mo,20,536,名高危患者,摘自,Heart Protection Study Collaborative Group,Lancet,2002,;360:7-22,;,MRC/BHF Heart Protection Study Collaborative Group,Eur,Heart J,1999;20:725-741;HPS Group communication.,心脏保护研究,(HPS),高危人群分布,冠心病,7,414,糖尿病,2,912,其它血管疾病,3,168,1,981,1,070,3,991,周围血管疾病,=6,748,中风=3,280,治疗中的,高血压患者,=8,457,DM=5,963,CHD=13,386,HPS,入组病人更接近临床病人,*包括冠脉及非冠脉血管再通手术.,摘自,Heart Protection Study Collaborative Group,Lancet,2002;360:7-22.,HPS：,舒,降之,40mg,对 不同血管事件的作用,患者百分比,%,0,15,5,10,安慰剂,(,n=10,267),舒降之,(,n=10,269),相对危险性,=,27%,p0.0001,主要冠脉事件,11.8%,8.7%,中风,5.7%,4.3%,血管再通手术*,11.7%,9.1%,相对危险性,=,25%,p0.0001,相对危险性,=,24%,p0.0001,发生事件,患者数,1212,898,585,444,1205,939,HPS,研究：心梗与血管再通术,0.4,0.6,0.8,1.0,1.2,1.4,Nonfatal MI,Coronary death,Subtotal:MCE,Coronary,Noncoronary,Subtotal:any RV,Any MVE,Coronary events,Revascularizations,Type of Major,Vascular Event,Statin,-,Allocated,(n=10269),Placebo-,Allocated,(n=10267,),357(3,.5%),574(5,.6%),587(5,.7%),707(6,.9%),898(8,.7%),1212(11,.8%),513(5,.0%),725(7,.1%),450(4,.4%),532(5,.2%),939(9,.1%),1205(11,.7%),2033(19,.8%),2585(25,.2%),0.73(0.67,0.79),P,0.0001,0.76(0.70,0.83),P,0.0001,0,.76(0.72,0.81),P,0.0001,Statin,Better,Placebo Better,Heart Protection Study Collaborative Group,.Lancet.,2002;360:7,22.,冠脉血管再通术需求下降,30%,非冠脉血管再通术需求下降,16%,*根据(,NCEP)ATP III,指南，,LDL-C 100 mg/dl,是理想的治疗目标水平。另外两个血脂水平在随机分组前巳根据,NCEM,指南所界定。,摘自,MRC/BHF Heart Protection Study Final Results.Presented at the European Atherosclerosis Society.Salzburg,Austria,July 2002 (,www.ctsu.ox.ac.uk,).,LDL-C,基线水平(,mg/,dL,)*,100,(n=3421),100 130,(n=7068),130,(n=10,047),21.0%,16.4%,24.7%,18.9%,26.9%,21.6%,0,10,20,30,患者百分比,%,安慰剂,(n=10,267),舒降之,(n=10,269),HPS:不同,LDL,基线水平患者的5年主要血管事件,舒降之,40mg,的益处不受基线血脂水平影响,SE=standard error of the mean,摘自,Heart Protection Study Collaborative Group,Lancet,2002,;360:7-22,.,舒,降之,40mg:,持续使用 带来更大临床益处,安慰剂,舒降之,随访年期,患者百分比,%,0,1,2,3,4,5,6,10,20,30,0,每1000名分布舒降之,治疗患者所获得的益处,(平均,SE),5 3,20 4,35 5,46 5,5,4,7,60 18,危险性下降,24%,(,p0.0001),HPS研究中舒降之40mg