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1、脑卒中高危患者的识别和治疗 一级预防的重要策略,Atherothrombosis*is aLeading Cause of Death Worldwide1,1.The World Health Report 2001.Geneva:WHO;2001.,Mortality(%),*Cardiovascular disease,ischemic heart disease and cerebrovascular diseaseWorldwide defined as Member States by WHO Region(African,Americas,Eastern Mediterranea
2、n,European,South-East Asia and Western Pacific),心脑血管的发病率脑卒中与心肌梗死发病率比较(每1000人年),脑卒中 心肌梗死Syst-Eur13.78.0Syst-China20.82.4,高血压患者发生脑卒中较心梗更常见-基于11项大型随机化临床干预试验的荟萃分析,STOP-1 SHEPSTONE*SYST-EURSYST-CHINA*HOTCAPPPSTOP-2NICS+NORDILINSIGHT,7672677067615376706067,162747361632469523941879010985661441410886575,822
3、695212410429434045220355141,53165478162093272934340138,平均年龄(岁),随机患者 人数,脑卒中数,MI数,试验名称,总数 59550 2233 1627,Kjeldsen SE et al.Blood Pressure 2001;10:190-2,*该两项在中国进行+此项在日本进行,脑卒中,冠心病,其它心血管病,中国人群脑卒中和冠心病死亡在总的心血管病死亡中所占比例,Adapted from Reddy KS Circulation 1998,97:596,高血压是脑卒中的 重要危险因素,Consequences of Hypertensi
4、on1-4,Hypertension,BrainHeartKidney,End-stage renal disease,MI,heart failure,sudden death,Stroke,dementia,1.Weir et al.Am J Hypertens 1999;12:205S-213S.2.Beers MH,Berkow R,eds.The Merck Manual of Diagnosis and Therapy.17th ed.1999:1629-1648.3.Francis CK.In:Izzo JL Jr,Black HR,eds.Hypertension Primer
5、:The Essentials of High Blood Pressure.2nd ed.1999:175-176.4.Hershey LA.In:Izzo JL Jr,Black HR,eds.Hypertension Primer:The Essentials of High Blood Pressure.2nd ed.1999:188-189.,7,高血压,增加动脉血管僵硬度,早期脉搏波的反射增加,升高与外周血压相关的中心收缩压,增加左室壁张力=左室肥厚,增加卒中的危险,周围阻力增加,增加脉搏波的速率,JNC 7 特殊高血压治疗中（老年高血压）,1、65岁以上人群三分之二以上患高血压.
6、2、这一人群有最低的血压控制率.3、治疗，包括对单纯收缩期高血压的治疗，同样应遵循一般高血压的治疗原则.4、应小剂量初始用药;为达靶目标可以使用标准剂量及联合用药.,预防卒中应按照 JNC 7中的治疗目标,降低心脑血管疾病和肾病的发生率和死亡率血压达到 140/90 mmHg能减少CVD并发症。SBP及DBP均应达标，在50岁以上的患者，治疗重点要放在SBP的达标上。糖尿病或慢性肾病患者降压目标是 130/80mmHg。SBP应达到目标血压，特别是50岁以上的人群。,1、至少将血压降至 SBP 140mmHg 和 DBP 90mmHg2、对糖尿病患者 SBP 130mmHg 和 DBP 80m
7、mHg3、对老年人 SBP 140mmHg有时甚为困难，仍然强调严格控 制血压,2003 ESC/ESH 降压治疗的目标,SBP,0,5,10,15,ACEI,B阻滞剂,钙拮抗剂,利尿剂,-,-,-,NS,NS,P0.005,Am J Hypentens 2001,14:241,对老年SBP高血压患者的药物交叉试验,Comparable Blood-Pressure Reductions1,1.Dahl?f B et al.Lancet 2002;359:995-1003.,17,AtenololLosartan,Systolic,Diastolic,Mean arterial,Atenolo
8、l 145.4 mmHg*,Atenolol 102.4 mmHg*,Atenolol 80.9 mmHg*,Losartan 144.1 mmHg*,Losartan 102.2 mmHg*,Losartan 81.3 mmHg*,*Mean BP at last visit.,mmHg,180,170,160,140,150,130,110,120,100,90,40,80,60,70,50,Time(months),42,36,24,30,12,18,6,0,48,54,Reduction in the Risk of Stroke1,No significant difference
9、in CV death and MI vs.atenolol.Risk reduction=relative risk vs.atenolol.,Losartan(n)4605 4528 4469 4408 4332 4273 4224 4166 4117 3974 1928 925Atenolol(n)4588 4490 4424 4372 4317 4245 4180 4119 4055 3894 1901 897,Number at risk,16,1.Dahl?f B et al.Lancet 2002;359:995-1003.,Atenolol,Proportion of pati
10、ents with first event(%),6,7,0,2,3,4,5,0,6,42,30,12,18,24,36,48,54,60,66,Time(months),Losartan,1,Adjusted risk reduction 24.9%,p=0.0010Unadjusted risk reduction 25.8%,p=0.0006,Fatal and nonfatal stroke,8,Reduction in Risk of Stroke in Patients with ISH,1.Kjeldsen SE et al.JAMA 2002;288:1491-1498.,At
11、enolol 666 650 630 621 606 593 579 568 562 536 245 99Losartan 660 651 640 628 618 605 595 581 577 551 266 108,Numberat risk,19,8,10,6,4,0,2,Proportion of patients with first event(%),0,6,42,30,12,18,24,36,48,54,60,66,Time(months),Atenolol,Losartan,Adjusted risk reduction 40%,p=0.02,Fatal and nonfata
12、l stroke,No significant difference in MI vs.atenolol.,40%,0,150,145,140,135,130,1,2,3,4,5,6,0,90,85,80,75,70,1,2,3,4,5,6,随访(年),随访(年),平均收缩压,平均舒张压,mmHg,mmHg,氯噻酮,氨氯地平,赖诺谱利,与氯噻酮组相比，氨氯地平组收缩压高0.8mmHg(P=0.03)，赖诺普利组高 2mmHg(P0.001)；氨氯地平组舒张压低 0.8mmHg(P0.001)。赖诺普利在老年人收缩压较氯噻酮组高3mmHg，在黑人高4mmHg。,ALLHAT:预先设定的心血管次要
13、终点,氨氯地平与氯噻酮比较,*CHD,coronary revascularization,or hospitalized angina.CHD,stroke,coronary revascularization,all angina,all congestive heart failure,or peripheral arterial disease.,ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group.Major outcomes in high-risk hypertensive pat
14、ients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic:the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT).JAMA.2002;288:2981-2997.,NORVASC(amlodipine besylate),P=0.20P=0.97P=0.12P=0.20,因 此,治疗高血压，特别在控制SBP的达 标是预防脑卒中的关键,左室
15、肥厚是脑卒中的重要 危险因素,Verdecchia P et al,Circulation 2001;104:2039-2044.,高血压患者脑血管事件危险与24小时动态血压和左室乘积指数的关系,0,10,20,30,40,50,60,No LVH,Borderline LVH,LVH,Men,Women,(%),Incidence of Stroke According to LVH Status,抗高血压治疗逆转左心室肥厚的作用,经治疗时间校正的均值和95%可信限。*p0.01,不同类型药物之间。p0.10,不同类型药物之间。Schmieder RE et al.JAMA.1996;275
16、:1507?513.,左心室重量指数的变化(%),0,-5,-10,-15,-20,-25,利尿剂,b阻滞剂,钙拮抗剂,ACE抑制剂,*,7%,6%,9%,13%,LIFE:科素亚与阿替洛尔在逆转LVH的比较,-18,-16,-14,-12,-10,-8,-6,-4,-2,0,Cornell Product,Sokolow-Lyon,自基线的平均改变(%),p0.0001,Dahlf B et al Lancet 2002;359:995-1003.,10.2%,9.0%,15.3%,4.4%,p0.0001,心房纤颤 是脑卒中的重要危险因素,AF-对脑卒中的流行病学资料,AF卒中发生率-心脏
17、情况相关“孤立”AF(75岁占半数，老年女性致残主要原因HCM AF常伴发，卒中及体循环栓塞 2.4-7.1%/年,(2)危险因素,危险因素相对危险卒中或TIA史2.5高血压史1.6充血心衰1.4高龄(每10年递增)1.4糖尿病1.7冠心病1.5,1.NVAF中缺血卒中和体循环栓塞相对危险,NVAF预防抗血栓,药物 栓塞事件(%年)RR(%)p值华法令1.4(80%)对照 4.5680.00140+%阿斯匹林6.3 21 对照8.1=0.05,结论：预防血栓栓塞事件:华法令-重要地位阿斯匹林-中等效果。,一级临床试验(n=6500+，65-80岁),Reduction in Risk of S
18、troke in Patients with AF1,1.Dalhf B et al.Presented at the European Society of Cardiology Congress;Berlin,Germany;August 31September 4,2002.Poster 2163.,29,Adjusted risk reduction 49%,p=0.018,Proportion of patients with first event(%),0,6,42,30,12,18,24,36,48,54,60,66,Time(months),Atenolol,Losartan
19、,20,25,15,10,5,0,Fatal and nonfatal stroke,无危险因素为何可以接受阿斯匹林 325mg/d,原发事件(缺血卒中，致残，TIA)卒中/栓塞 2.2%/年(95%CI 1.6-3.0%)颅内出血 0.1%/年，非CNS出血 0.6%/年高血压史(46%)有 无年事件率 3.6%1.1%致残卒中 1.4%0.5%,SPAF III 亚组-低危防治血栓(n=892)AF1年内无危险因素，之后6.5%出现危险因素，改药。共随诊 2 年,阵发性AF者，如果症状不严重，可不治疗持久性AF者，控制HR+抗凝治疗持续性AF者心率控制可作为一线治疗如果心律控制不易做到，尽
20、早放弃ACC/AHA/ESC指南认为心律控制应优先选择在治疗持续性AF上心律与心率控制是等效的，因此也可能修改指南，更强调心率控制治疗,AF.新指南的理解,因 此,纠正房颤、积极的抗凝治疗，控制心室率及降压治疗 是预防脑卒中的关键,无症状性颈动脉狭窄,心血管健康研究中65岁者，7%男性和5%女性颈动脉狭窄50%弗明汉队列研究中，66至93岁年龄组，7%女性及9%男性颈动脉狭窄50%,Internal Carotid,Carotid Bulb(lesion prone site),Flow Divider,External Carotid,Common Carotid Artery,Pulsat
21、ile Hemodynamics and Shear Stress,2003 ESC/ESH,抗高血压治疗的获益并非来源于所用的降压药物，而主要是取决于血压降低本身但亦有证据表明，不同类别的抗高血压药物具有特别的临床益处ARB脑卒中利尿剂心力衰竭ACE抑制剂/ARB肾功能恶化ARB左心室肥厚钙拮抗剂颈动脉粥样硬化,0,.,0,5,0,.,0,4,0,.,0,3,0,.,0,2,0,.,0,1,0,.,0,0,-,0,.,0,1,P,=,0,.,0,0,7,0,1,2,2,4,3,6,PREVENT：氨氯地平对B超测定的颈动脉内膜中层厚度（IMT）的作用,内膜中层厚度变化,(mm),Circul
22、ation in Press,安慰剂,氨氯地平,月,Impact on Intima-Media Thickness,Follow-up(years),IMT Change from baseline(mm),0,-0.010,0,0.010,0.020,0.030,0.040,1,2,3,4,HCTZ/Amiloride,Nifedipine GITS,Progression,Regression,Simon et al:Circulation 2001;103:2949-2954,INSIGHT,随机，双盲，218 名高血压患者随 4年，依那普利 10-20 mg/天，洛活喜 5-10 m
23、g/天，依那普利组IMT减少的 0.08 mm,而服用洛活喜的患者IMT减少了的 0.11 mm,P0.05.,洛活喜及依那普利在消除IMT的作用,ESC Congress 2002.?,Total Cholesterol and Stroke,MRFIT 20 year follow-up U-shaped curve TC220mg/dL:ppositive relationship with ischemic stroke,Tirschwel DL StudyComparison of three groups:Ischemic stroke 587 patients Hemorrhag
24、ic stroke 137 patients Healthy control 3743 Results:TC280mg/dL vs TC 230mg/dL ischemic stroke 2:1 TC180mg/dL vs TC 230mg/dL hemorrhagic stroke 2:1 High TC 10-15%ischemic stroke Low TC 7%hemorrhagic stroke Optimal TC level for stroke:200 mg/dL,AHA 1999,Ischaemic Stroke,placebotreated reductionPrimary
25、 preventionWoscops 51 46 10%Secondary preventionCARE 78 54 31%4S 98 70 30%,Hebert et al JAMA 1997;278:313-21,Ischaemic Stroke Reduction in Statin Trials,总体心血管危险的威胁,Kannel WB.In:Genest J,et al,eds.Hypertension:Physiopathology and Treatment.New York,NY:McGraw Hill;1977:888-910.,血脂异常TC 5.4 mmol/L(210 m
26、g/dL)X1.3,高血压SBP 165 mm HgX1.9,糖耐量异常X1.8,X2.6,X4.5,X3.5,X2.3,血脂异常TC 6.1 mmol/L(235 mg/dL)X1.7,高血压SBP 195 mm HgX3.0,吸烟X1.7,X5.3,X8.7,X5.2,X2.9,ASCOT 试验设计,设计,ASCOT 立普妥组和安慰组血压控制一致,收缩压(mm Hg),舒张压(mm Hg),基线164/95治疗后138/80,LLA 结束,LLA 结束,结果,Sever PS,et al,Lancet.2003;361:1149-58,ASCOT:总胆固醇和LDL-C的降低,200,150
27、,150,75,125,100,100,(mg/dL),(mg/dL),总胆固醇(mmol/L),LDL-C(mmol/L),年,1.3 mmol/L,1.1 mmol/L,1.2 mmol/L,1.0 mmol/L,LLA 结束,2,4,6,0,1,2,3,立普妥 10 mg,安慰剂,1,2,3,4,0,1,2,3,结果,Sever PS,et al,Lancet.2003;361:1149-58,降低27%,HR=0.73(0.56-0.96),p=0.0236,立普妥 10 mg事件数 89安慰剂事件数 121,结果,Sever PS,et al,Lancet.2003;361:1149-58,ASCOT:立普妥进一步显著降低27%的脑卒中,立普妥治疗组脑卒中的显著降低也使试验提前结束,脑卒中的一级防治策略,1、重视对心脑血管的危险分层，以筛选出高 危的脑卒中患者。2、积极有效的干预有可能导致脑卒中的心血 管危险因素。,谢 谢,
