课件：血脂调整与脑卒中的预防.pptVIP

血脂调整与脑卒中的预防,复旦大学上海医学院中山医院神经内科 汪 昕,脑卒中在中国,MONICA 研究：我国患病率低于日本，芬兰等高发区， 而高于大多数工业化和发展中国家，位于前列。 我国脑卒中的患病率、死亡率在疾病谱中一直处于前三位。 全国脑卒中年发病率约为110180/10万； 年死亡率约为 80120/10万 (城市人口患病率约为600700/10万；农村人口患病率约为300/10万） 脑卒中是死亡的主要原因之一，超过70% 的幸存者伴不同 程度的功能障碍(残疾)。,医疗卫生人员心血管病防治知识 陶寿淇，武阳丰主编,研究背景,脑卒中的年龄性别死亡率(1999),来源：中国卫生统计提要 1999,研究背景,北京25-74岁人群急性脑卒中标化发病率,王文化，等，中华流行病学杂志 2001(4)：269-271,研究背景,卒中危险性下降,随访时间（年）,发生事件患者的比例,安慰剂,药物治疗*,危险性下降28% (95%的可信限 17-38%) P0.0001,Reference: Lancet 2001; 358: 1033-41,0.20 0.15 0.10 0.05 0.00,1,2,3,4,研究背景,显著降低中风事件,S.Yusuf, et al NEJM 2000;342:145-153,研究背景,CURE: Clopidogrel in Patients with a Previous Stroke1,1. Data on file, 2002, p87 internal CSR-EFC 3307.,*Number of events prevented/1,000 patients treated On top of standard therapy (including ASA),上海市城市综合干预中风发病情况(1991-2000),研究背景,Relationship between lipids and stroke risk,Mixed results in trying to identify an association between cholesterol and stroke Most studies measured total cholesterol Did not look at LDL cholesterol Did not distinguish among stroke subtypes Early meta-analyses suggested no relationship More recent studies show an effect for athero-thrombotic strokes,他汀类 与,脑卒中 一二级预防,他汀类药物一二级预防历史,有冠心病或心梗 伴高胆固醇患者,冠心病/心梗高危的中等胆固醇升高患者,冠心病/心梗但胆固醇正常患者,非冠心病/心梗的高胆固醇患者,没有冠心病史/心梗，一般TC及LDL-C水平，但伴低HDL-C水平患者,4S,PLAC I/II, KAPS, REGRESS,CARE,WOSCOP,AFCAPS/TexCAPS,HPS,他汀类药物临床研究 二级预防 4S CARE LIPID 一级预防 WOSCOPS AFCAPS / TexCAPS 同时包括一、二级预防 HPS,缺血性中风,安慰剂 治疗组 降低 一级预防 Woscops 51 46 10% 二级预防 CARE 78 54 31% 4S 98 70 30%,Hebert et al JAMA 1997; 278: 313 - 21,他汀类药物临床试验：中风的减少,Pravastatin Pooling Project Results: Total Stroke,Event Rates/ 1000/year,10 5 0,Byington et al. Circulation. 2001;103:387-392.,CARE/LIPID N=13,173 (Events=501),22% (P=0.01),All Trials N=19,768 (Events=598),20% (P=0.01),Fatal and Nonfatal Stroke,Placebo,Pravastatin,心 脏 保 护 研 究 Heart Protection Study,HPS亚组数据：卒中,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,4S3,4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,稳定 CAD,MIRACL,AFCAPS / TexCAPS/ WOSCOPS,Duration of follow-up: 15.0 years; 26.1 years; 35.4 years; 4 XXyears.,Randomization: 2496 h,CARE1/LIPID2,Randomization: CARE - 320 mo LIPID - 336 mo,HPS设计,5年 N=20,536例患者(3,280例有脑血管疾病，17,256例患者有其他阻塞性动脉疾病或不合并脑血管疾病的糖尿病) 舒降之 40 mg，或相匹配的安慰剂治疗 LDL胆固醇水平平均相差1.0 mmol/L (39 mg/dL),参加HPS病人的基线特点,基线血脂 (mmol/L) 和载脂蛋白 (g/L),治疗安排,结 果,(10269),(10267),辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,类型,290,409,缺血性,51,53,出血性,103,134,不明,严重性,96,119,致死性,42,51,严重,107,155,中度,138,189,轻度,61,71,不明,(4.3%),(5.7%),25% SE 5,减少,444,585,(2P0.00001),所有卒中,0.4,0.6,0.8,1.0,1.2,1.4,HPS: 卒中发病率,结果1,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基础,特征,(10269),(10267),年龄 (岁), 65,164,195,(3.3%),(4.0%),65 70,110,154,(4.5%),(6.3%), 70,170,236,(5.8%),(8.2%),性别,男,331,453,(4.3%),(5.9%),女,113,132,(4.4%),(5.2%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按年龄、性别的卒中发病率,结果2,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基础,特点,(10269),(10267),既往 冠心病,是,265,347,(4.0%),(5.2%),否,179,238,(5.0%),(6.7%),既往脑血管病,是,169,170,(10.3%),(10.4%),否,275,415,(3.2%),(4.8%),既往糖尿病,是,149,193,(5.0%),(6.5%),否,295,392,(4.0%),(5.4%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按既往疾病的卒中发病率,结果3,2019/8/7,25,可编辑,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基线,特征,(10269),(10267),既往冠心病,是,175,237,(2.6%),(3.5%),否,115,172,(3.2%),(4.8%),既往脑血管病,是,100,122,(6.1%),(7.5%),否,190,287,(2.2%),(3.3%),既往糖尿病,是,102,140,(3.4%),(4.7%),否,188,269,(2.6%),(3.7%),所有病人,290,409,(2.8%),(4.0%),30% SE 6,减少,(2P0.00001w4),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按既往疾病的 缺血性卒中,结果4,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基线,特点,(10269),(10267),既往冠心病,是,1459,1841,(21.8%),(27.5%),否,574,744,(16.1%),(20.8%),既往脑血管病,是,406,488,(24.7%),(29.8%),否,1627,2097,(18.9%),(24.3%),既往糖尿病,是,601,748,(20.2%),(25.1%),否,1432,1837,(19.6%),(25.2%),所有病人,2033,2585,(19.8%),(25.2%),24% SE 3,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按既往疾病的主要血管事件,结果5,主要血管事件的绝对效果以及按既往脑血管病的卒中,S,S,P,P,Yes No 既往脑血管病,主要血管事件 (%),20% (6) 58 (18) p=0.001,25% (3) 60 (7) p0.0001,其他事件,卒中,结果6,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基线,特点,(10269),(10267),LDL 胆固醇 (mmol/L), 3.0,137,194,(4.0%),(5.7%), 3.0 3.5,108,155,(4.2%),(6.2%), 3.5,199,236,(4.6%),(5.4%),HDL 胆固醇 (mmol/L), 0.9,170,199,(4.7%),(5.6%),0.9 1.1,115,166,(4.1%),(5.8%), 1.1,159,220,(4.1%),(5.7%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按基线血脂的卒中发病率,结果7,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基线,特点,(10269),(10267),舒张压 (mmHg), 80,176,239,(3.9%),(5.2%),80 90,131,185,(4.0%),(5.8%),90,137,160,(5.6%),(6.5%),收缩压 (mmHg), 140,162,189,(3.6%),(4.2%),140 160,121,169,(3.9%),(5.3%),160,161,226,(6.1%),(8.8%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按基线血压的卒中发病率,结果8,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,基线,特点,(10269),(10267),高血压治疗,是,223,274,(5.3%),(6.5%),否,221,311,(3.6%),(5.2%),阿斯匹林,是,286,378,(4.4%),(5.8%),否,158,207,(4.2%),(5.5%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS: 按高血压治疗和使用阿斯匹林卒中 发病率,结果9,辛伐他汀,安慰剂,RR & 95% CI,他汀更好,安慰剂更好,随访年,(10269),(10267),1,87,106,(0.8%),(1.0%),2,81,132,(0.8%),(1.3%),3,82,111,(0.8%),(1.2%),4,81,111,(0.9%),(1.2%),5+,113,125,(1.2%),(1.4%),所有病人,444,585,(4.3%),(5.7%),25% SE 5,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,HPS : 按年卒中的发病率,结果10,随访年限,安慰剂,辛伐他汀,效益/1000(SE),2(1),7(2),10(2),13(3),14(4),15(10),Logrank p0.0001,0,1,2,3,4,5,6,0,1,2,3,4,5,6,7,卒中比例,HPS: 按年卒中,结果11,HPS: Adverse Events,结果12,他汀,安慰剂,RR & 95% CI,STATIN better,PLACEBO better,研究,GREACE,9,17,(1.1%),(2.1%),AFCAPS/TexcAPS,14,17,(0.4%),(0.5%),Post-CABG,18,16,(2.7%),(2.4%),GISSI,20,19,(0.9%),(0.9%),WOSCOPS,46,51,(1.4%),(1.5%),CARE,52,76,(2.5%),(3.7%),SSSS,56,76,(2.5%),(3.4%),ASCOT,89,121,(1.7%),(2.4%),PROSPER,135,131,(4.7%),(4.5%),LIPID,169,204,(3.7%),(4.5%),ALLHAT,209,231,(4.0%),(4.5%),HPS,444,585,(4.3%),(5.7%),所有病人,1261,1544,(3.0%),(3.6%),21% SE 4,减少,(2P0.00001),0.4,0.6,0.8,1.0,1.2,1.4,主要他汀试验的卒中影响,Mechanisms of Action,Lipid lowering is not the entire answer Benefits seen in patients with relatively normal levels Plaque stabilization Anticoagulant effects (fibrinogen, PAI-1) Reduces C-reactive protein Improves cerebral vasomotor reactivity Modulates brain