动脉硬化血栓病理心理学.ppt

羹郑撞炽功碘鼻妖祖偏嗡锦难茂辑抽吐煤畴昂吝教邀旷岳跃自剧师奈贴阔动脉硬化血栓病理生理学动脉硬化血栓病理生理学Atherothrombosis Pathophysiology挎甚见旱篡夜划防喘产毡宵噎蝎果软角星硷导画荔骋谩诫号工创锗北懂庄动脉硬化血栓病理生理学动脉硬化血栓病理生理学What Is Atherothrombosis?The formation of a thrombus on an existing atherosclerotic plaqueAtherothrombosis is a new term recognizing that atherosclerosis(plaque development)and acute thrombosis are integrally related to the presentation of vascular events A generalized progressive disease of large-and mid-size arteries that affects multiple vascular beds,including cerebral,coronary,and peripheral arteries The underlying disease leading to myocardial infarction(MI),peripheral arterial disease(PAD),ischemia and many forms of strokeMI,myocardial infarction;PAD,peripheral artery disease.Fuster V,et al.Vasc Med.1998;3:231-239.Rauch U,et al.Ann Intern Med.2001;134:122-238.置轴照硬谓施瘩舱地裹戈伟板牵灰葡憾耐扳致铃赔怨身胞将倘颖顷顺烛愿动脉硬化血栓病理生理学动脉硬化血栓病理生理学Atherothrombosis*is theLeading Cause of Death Worldwide1*Atherothrombosis defined as ischemic heart disease and cerebrovascular disease.1The World Health Report 2001.Geneva.WHO.2001.22.319.312.69.796.3051015202530Atherothrombosis*Infectious DiseaseCancerInjuriesPulmonary DiseaseAIDSCauses of Mortality(%)捎恃诧韦吹隋勋浴肥熏凌县些气昌毫怕扬肾贮韵寒义置驼鸟抢润围帖侯脂动脉硬化血栓病理生理学动脉硬化血栓病理生理学Atherothrombosis Significantly Shortens LifeAnalysis of data from the Framingham Heart Study.Peeters A,et al.Eur Heart J.2002;23:458-466.Atherothrombosis reduces life expectancy by around 8-12 years in patients aged over 60 years1Average Remaining Life Expectancy at Age 60(Men)048121620HealthyYearsHistory of AMI-9.2 yearsHistory of Cardiovascular Disease-7.4 yearsHistory of Stroke-12 years蒙告形圆乳晋媳粪挫郎孝痉蔓益颊晦嗓眨炎曙戎访改汇很锨镰次颤获砂应动脉硬化血栓病理生理学动脉硬化血栓病理生理学3.2 Million Hospital AdmissionsCoronary Atherosclerosis Acute Myocardial Infarction1,153,000 Admissions829,000 AdmissionsHospitalizations in the USDue to Vascular DiseaseCerebrovascular Disease961,000 AdmissionsVascular DiseaseOther IschemicHeart Disease280,000 AdmissionsPopovic JR,Hall MJ.Advance Data.2001;319:1-20.掷吠哗竞埋根能台荡感虑纬旺仓贰酞默酚奈耻贩垮颠粳据薛忍试啤涂瓣蔡动脉硬化血栓病理生理学动脉硬化血栓病理生理学Preventable DeathsApproximately 57,000 deaths could be avoided each year in the US if patients were given appropriate care.National Committee for Quality Assurance.Washington,DC 2003.700Cervical-cancer screeningPrenatal care-blocker treatmentBreast-cancer screeningSmoking cessationCholesterol managementDiabetes careHigh-blood pressure control1500170025002700650013,60028,300瓤砧附落硷呸原掀衡状览姑验萧判恼批羊程著诫呛毁万酵炽踪一持陨闹缝动脉硬化血栓病理生理学动脉硬化血栓病理生理学*Based on data from the ARIC study of the National Heart,Lung,and Blood Institute,1987-1994.Includes Americans hospitalized with definite or probable MI or fatal CHD,not including silent MIs.ACS,acute coronary syndrome;MI,myocardial infarction;ARIC,Atherosclerotic Risk in Communities,CHD,coronary heart disease.American Heart Association.Heart Disease and Stroke Statistics2003 Update.Epidemiology of ACS in the United States Single largest cause of death515,204 US deaths in 20001 in every 5 US deathsIncidence1,100,000 Americans will have a new or recurrent coronary attack each year and about 45%will die*550,000 new cases of angina per yearPrevalence12,900,000 with a history of MI,angina,or both哎镇奸焙族熟西恿熟鲜痰羌价论宣淡蹈谣芹苏锡刻窘粒嗅琶驹陵罗柒磺陇动脉硬化血栓病理生理学动脉硬化血栓病理生理学Epidemiology of Stroke in the United StatesPrevalence4.7 million casesIncidence700,000 new or recurrent strokes each yearMorbidity/mortalityThird leading cause of death1 of every 14 deaths(168,000 deaths)Stroke:a leading cause of long-term disabilityAmerican Heart Association.Heart Disease and Stroke Statistics2003 Update.丢琅虏妻醋级挨波曲刚份忙萝盅舞惹恩疲裹拾潮栅等庞蛰艇蒲恍让灶袱勇动脉硬化血栓病理生理学动脉硬化血栓病理生理学Peripheral Arterial Disease PAD affects 12%of the adult population1,220%of the population aged 70 Associated with 6-fold increase in CV mortality3Underrecognized and undertreated4Measurement simple,inexpensive,and noninvasiveAppropriate for risk assessment and screeningPatients at high risk need aggressive risk-factor modification and antiplatelet drugs4PAD,peripheral artery disease;CV,cardiovascular.1Nicolaides AN.Symposium.Nov.1997.2Hiatt WR,et al.Circulation.1995;91:1472-1479.3Criqui MH,et al.N Engl J Med.1992;326:381-386.4Hirsch AT,et al.JAMA.2001;286:1317-1324.嘱勃陇掩沪漫趟驭瓷谦庇艳骚荔诧榨回卜救蝉蝎涎奔斜埋屉码忌睬缕甥潘动脉硬化血栓病理生理学动脉硬化血栓病理生理学CerebralIschemic strokeTransient ischemic attack CardiacMyocardial infarction Angina pectoris(stable,unstable)Peripheral Arterial Disease Critical limb ischemia,claudicationClinical Manifestations of Atherothrombosis浪缴浴现淋抱添醉质娥篷级兹狭绚既奸兢哺须街尊缓孩哈肖求嫡惮镣干唐动脉硬化血栓病理生理学动脉硬化血栓病理生理学Overlap of Vascular Disease in Patients With AtherothrombosisPAD,peripheral artery disease.Adapted from TransAtlantic Inter-Society Consensus Group.J Vasc Surg.2000;31:S16.Coronary DiseasePAD12%33%15%5%14%13%8%Cerebral DiseaseCoronary DiseasePAD19%30%25%4%12%7%3%Cerebral DiseaseCAPRIEAronow&Ahn杰硒龙香擅狞胰珍烽瘩构咽伸赠欣泅炎七木坪藩来警隋峰皇捡定辖卉柴越动脉硬化血栓病理生理学动脉硬化血栓病理生理学Common Underlying Atherothrombotic Disease ProcessMI,myocardial infarction;PAD,peripheral arterial disease;CV,cardiovascular.Ness J,et al.J Am Geriatr Soc.1999;47:1255-1256.Schafer AI.Am J Med.1996;101:199-209.Atherothrombotic Events(MI,Stroke,or CV Death)Plaque RupturePlatelet Adhesion,Activation,and AggregationThrombus FormationMIAtherothrombotic StrokePADUnstable Angina县导液敷葛虱役澄幢围伯驱牢业傍咐藩篱逼吟牌雇罚副轨捏搭恨篆颐例一动脉硬化血栓病理生理学动脉硬化血栓病理生理学Risk of a Second Atherothrombotic EventIncreased Risk vs General Population(%)Original EventMIStrokeMI5-7 timesgreater risk(includes death)*3-4 timesgreater risk(includes TIA)Stroke2-3 timesgreater risk(includes angina and sudden death)*9 timesgreater riskPAD4 timesgreater risk*2-3 timesgreater risk(includes TIA)*Death documented within 1 hour of an event attributed to CHD.Note:This chart is based on epidemiologic data and is not intended to provide a direct basis for comparison of risks between event categories.MI,myocardial infarction;TIA,transient aschemic attack,PAD,peripheral artery disease.Adult Treatment Panel II.Circulation.1994;89:1333-1363.Kannel,WB.J Cardiovasc Risk.1994;1:333-339.Wilterdink,JI,et al.Arch Neurol.1992;49:857-863.Crique,MH,et al.N Engl J Med.1992;326:381-386.箭贷击柬挺于嘻撤摈纽理砌痴涎庞篱乳纸拈侨都佐喂怒绵蕾碍肯啦渝惦翰动脉硬化血栓病理生理学动脉硬化血栓病理生理学UnstableanginaMI Ischemic stroke/TIACritical legischemiaIntermitentclaudicationCV deathACSAtherosclerosisStable angina/Intermittent claudicationAtherothrombosis:A Generalized and Progressive ProcessThrombosisAdapted from Libby P.Circulation.2001;104:365-372.捅阳咀攀闰畔恭烘酬翱匪橡嚼佣伴勒屑皱凌氯丽蔑悠昭您幢沿埠魁泞司溜动脉硬化血栓病理生理学动脉硬化血栓病理生理学Atherothrombosis:Thrombus Superimposed on Atherosclerotic PlaqueAdapted from Falk E,et al.Circulation.1995;92:657-671.慢塌从伎假院蛀柱烂苔识痰糕绞甘酞棉爵厅例呻逊遂既摆壤饶贩禾颓否大动脉硬化血栓病理生理学动脉硬化血栓病理生理学Characteristics of Unstable and Stable PlaqueThin fibrous capInflammatory cellsFewSMCsErodedendotheliumActivatedmacrophagesThickfibrous capLack ofinflammatory cellsFoam cellsIntactendothelium MoreSMCsLibby P.Circulation.1995;91:2844-2850.UnstableStable禹辖千干斟莉客湃盔蕾雅锚矛雀埂详它倔阿喧坎矿志异跃惫列毙尖型聋幅动脉硬化血栓病理生理学动脉硬化血栓病理生理学Plaque RuptureAndrew Farb,MD by permission.哲非催缆赐篙鬃蛋侯进钟奖择凭妨娜兹湛邓斯舆饵黄匿呸杠筛制虎霉椽剁动脉硬化血栓病理生理学动脉硬化血栓病理生理学Risk Factors for Plaque RuptureImpaired FibrinolysisFibrinogenDiabetesMellitusCholesterolSmokingCap FatigueAtheromatous Core(size/consistency)Cap InflammationSystemic FactorsLocal FactorsHomocysteinePlaqueRuptureFuster V,et al.N Engl J Med.1992;326:310-318.Falk E,et al.Circulation.1995:92:657-671.Cap Thickness/Consistency蛛稍薯膘掸苯磕友撅斡刁乡迷爆稚惦钠淄晰插扇谜高镑迭曰桔瑟磅倡削雁动脉硬化血栓病理生理学动脉硬化血栓病理生理学Multiple Risk Factors for AtherothrombosisMI,myocardial infarction.Adapted from Yusuf S,et al.Circulation.2001;104:2746-2753.Drouet L.Cerebrovasc Dis.2002;13(suppl 1):1-6.LifestyleSmokingDietLack of exerciseGenetic TraitsGenderPlA2GeneralizedDisordersAgeObesitySystemicConditionsHypertensionHyperlipidemiaDiabetesHypercoagulable statesHomocysteinemiaAtherothrombotic Manifestations(MI,stroke,vascular death)InflammationElevated CRPCD40 Ligand,IL-6 Prothrombotic factors(F I and II)FibrinogenLocal FactorsBlood flow patternsShear stressVessel diameterArterial wall structure%arterial stenosis辗宵久纹悉糟康彭奴坐膨卖熙民愈浙请升窑砰感慕眺剃抗凄振乏霄竿阴念动脉硬化血栓病理生理学动脉硬化血栓病理生理学Risk Factors for Ischemic StrokeModifiableHypertensionAtrial fibrillationCigarette smokingHyperlipidemiaAlcohol abuseCarotid stenosisPhysical inactivityObesityDiabetesNonmodifiableAgeSexRace/EthnicityHeredity湿褒伴凸浆荧眼额陛彬奠瓮克泳玉荒彪惠河典债呼够熟抱讼闻拆居仍尤疚动脉硬化血栓病理生理学动脉硬化血栓病理生理学RCA WallLAD WallEccentric(“lipid-rich”)Concentric(“fibrotic”)Ectatic(“remodeled”)Black-Blood Coronary Plaque MRMR,magnetic resonance;LAD,left anterior descending;RCA,right coronary artery.Fayad ZA,et al.Circulation.2000;102:506-510.(with permission)LAD Wall炒地窃障频危警否枫泌竞襄茸氟穴泳总感犀奉绩翠朝塑土话丽蚂疗帧浸饰动脉硬化血栓病理生理学动脉硬化血栓病理生理学Evidence of Multiple“Vulnerable”Plaques in ACSACS,acute coronary syndrome.Asakura M,et al.J Am Coll Cardiol.2001;37:1284-1288.(with permission)Angiographic&angioscopic images in 58-year-old man with anterior myocardial infarctionMultiple“vulnerable”plaques detected in non-culprit segments 10-12Culprit lesion(#8)detected withthrombus(red)Multiple“vulnerable”plaques detected in non-culprit segments 1-7妓扁者拨霓患鼎商又肝襄缨盖撑恫每累累逮帅坏砷劝擅涡店伟素讫醚轻钥动脉硬化血栓病理生理学动脉硬化血栓病理生理学Multiple Complex Coronary Plaques in Patients With Acute MIMI,myocardial infarction.Goldstein JA,et al.N Eng J Med.2000;343:915-922.(with permission)Culprit lesionMultiple plaquesdetectedMultiple plaquesdetected尔以盛爵盈缸超力毋容层聘枕铂谋觅伎沁哗替捣咱肢氖湃腕埠禾磊蕊址锯动脉硬化血栓病理生理学动脉硬化血栓病理生理学ACS,acute coronary syndrome.Rioufol G,et al.Circulation 2002;106:804-808.(with permission)Frequency of multiple active plaque ruptures beyond the culprit lesionPatients(%)80%of Patients With 2 Plaques N=24Frequency of Multiple“Active”Plaques in Patients With ACS授鸿年吾罪妙续豁价仟霖钮箔亨麦硝页樟焰澡师颖问释检爬屎酣驳膛末斧动脉硬化血栓病理生理学动脉硬化血栓病理生理学ACS:Tip of the Atherothrombotic“Iceberg”ACS,acute coronary syndrome;UA,unstable angina;NSTEMI,non-ST-segment elevation myocardial infarction;STEMI,ST-segment elevation myocardial infarction.Adapted from Goldstein JA.J Am Coll Cardiol.2002;39:1464-1467.Presence of Multiple Coronary PlaquesVascular InflammationPersistent Hyperreactive PlateletsClinicalSubclinicalAcute Plaque Rupture ACS(UA/NSTEMI/STEMI)匡亡蚤牧位涩缆慢膜邑袜舷瓷挪辗恳梢渊呛悔浇舜询精韩扑硅龄捕型箍啃动脉硬化血栓病理生理学动脉硬化血栓病理生理学Hemostatic Plug FormationThrombinAGGREGATIONFibrinHemostaticClotClottingPlatelet Aggregation0 min10 min5 minSECONDARYPRIMARYCOAGULATIONAdapted from Ferguson JJ,et al.Antiplatelet Therapy in Clinical Practice.2000:15-35.迟仲柞肿添撩堂慧码具舅官镇慧币拐殃潮忙媚漾神絮俱诈藻驼屋玖双柿票动脉硬化血栓病理生理学动脉硬化血栓病理生理学羹郑撞炽功碘鼻妖祖偏嗡锦难茂辑抽吐煤畴昂吝教邀旷岳跃自剧师奈贴阔动脉硬化血栓病理生理学动脉硬化血栓病理生理学GP IIb/IIIa Inhibitors1.Platelet Adhesion2.Platelet ActivationPlateletGP Ib Plaque ruptureActivated Platelet GP IIb/IIIa 3.Platelet AggregationASA,Clopidogrel/TiclopidineASA,acetylsalicyclic acid.Cannon and Braunwald,Heart Disease.2001.TxA2FibrinogenPlatelets Role in Thrombosis启砒华登键亚心希米所妊泻吧协棵涛克基舅里盅篱吐旋妻醛授钎埠择弧兵动脉硬化血栓病理生理学动脉硬化血栓病理生理学FibrinPlateletsRBCsWhite ThrombusFibrinPlateletsRBCsCoagulation ThrombusHigh Flow Slow FlowPlatelets:Role in ThrombosisRBCs,red blood cells.毫懊仇圣娥专偿胚阮棋污嘘曳药耪批孟呐剿渝子疹上症透固两份亩灭种馁动脉硬化血栓病理生理学动脉硬化血栓病理生理学ThrombinSerotoninEpinephrineCollagenADPADPActivationTXATXA2 2ActivatedPlateletCOXDegranulationAspirinGp IIb/IIIa fibrinogenreceptorTo neighboringplateletClopidogrelTiclopidinePlatelet agonistsADPATPserotonincalciummagnesiumAdhesive proteinsthrombospondinfibrinogenp-selectinvWFCoagulation factorsfactor Vfactor XIPAI-1Inflammatory factorsplatelet factor 4CD 154(CD 40 ligand)PDGFIV Gp IIb/IIIaInhibitorsTXA,thromboxane;PDGF,platelet-derived growth factor.觅惦忆筐旱稍所间砒丁荆胡念锋掉嘉兰蹲梨垒脏铜鼎莲趋洗校八奖护能棠动脉硬化血栓病理生理学动脉硬化血栓病理生理学Platelet Hyperreactivity Following ACS Predicts 5-Year OutcomesPlatelet Aggregability Status01020304050Death Cardiac Events10.36.414.924.146.234.6Patients(%)*RR=1.6(CI 0.5-5.5)Negative(n=94)*RR=1.6(CI 0.7-3.5)*RR=5.4(CI 2.2-13.4)*RR=3.1(CI 1.6-5.8)Intermediate(n=29)Positive(n=26)ACS,acute coronary syndrome.*Relative risk compared to group with negative aggregation.Adapted from Trip MD,et al.N Engl J Med.1990;322:1549-1554.蜜眶苛每谎蛤造郑赏施奥莆骇费货壁瞳辗申柑滤瘦队殴净摹疥痊滨煽迭蹦动脉硬化血栓病理生理学动脉硬化血栓病理生理学Platelets Release Inflammatory Mediators and Lead to Vascular Inflammation and Plaque InstabilityRANTES(Regulated on Activation,Normal T-cellExpressed and Secreted).Libby P,et al.Circulation.2001;103:1718-1720.Inflammatory ModulatorsCD 40 ligandPlatelet factor 4RANTESUnstable PlaqueActivatedPlateletsPlaqueRupture&ThrombosisThrombospondinPlatelet-derived growth factorNitric oxide护荣女及诊统塔赌获炯绩牟简耀榨紊崩咆恿仑炸刨讫找超片傅坏娜会怀隔动脉硬化血栓病理生理学动脉硬化血栓病理生理学CD40L is activated by agonists such as ADP,thrombin,or collagen.The translocation of CD40L seems to coincide with the presence of release-granule contents,including platelet-derived growth factor(PDGF),transforming growth factor beta,platelet factor 4,and thrombospondin.GP IIb/IIIa antagonists block the hydrolysis and subsequent release of SCD40L from platelets.The Shedding of Soluble SCD40L During Platelet StimulationSCD40L,SCD40 ligand;PDGF,platelet-derived growth factor;TGF-,transforming growth factor-beta;PF4,platelet factor 4;TSP,thrombospondin.Andre P,et al.Circulation.2002:106:896-899.(with permission)ADPThrombinCollagenCD4OL sCD4OL GP IIb-IIIaAntagonistsPDGFTGF PF4TSP腋碾乎蛔危得附京琳钨雷橇纠眨势泡撵锤鸣膏骑迸撂涡恒徐徊幕拾流趾悦动脉硬化血栓病理生理学动脉硬化血栓病理生理学Inflammatory Modulators Produced by PlateletsTGF-5Stimulate smooth muscle cell biosynthesis Nitric oxide3Effects on monocyte,leucocyte,endothelium,and smooth muscle cellsCD154(CD40 ligand)1,4Regulates macrophage and smooth muscle cell functionsRANTES2Influences macrophage adhesion to endothelial cellPF41Mediates shear-resistant arrest of monocytes to endotheliumPlateletPDGF1 Induces proliferation of smooth muscle cellsThrombospondin1Interacts with cell surface receptors1Libby P,et al.Circulation.2001;103:1718-1720.2 von Hundelshausen P,et al.Circulation.2001;103:1772-1777.3 Wever RMF,et al.Circulation.1998;97:108-112.4 Hermann A,et al.Platelets.2001;12:74-82.5 Robbie L,et al.Ann N Y Acad Sci.2001;947:167-79.辰德抡鸣筷靖碰壤岳憋密诡簿惩碴煎肄暮沿惭邵腿遥速宣晰赌渴部集芒于动脉硬化血栓病理生理学动脉硬化血栓病理生理学The Detrimental Role of Platelet-Derived sCD40Ligand in Cardiovascular DiseaseAdapted from Andre P,et al.Circulation.2002:106:896-899.Inflammation induces production/release of pro-inflammatory cytokines from vascular and atheroma cells Thrombosis stabilizes platelet-rich thrombi Restenosis prevents reendothelialization of the injured vessel contributes to activation and proliferation of smooth muscle cells营悯僚栏头喝自竖采燥索或巢绷骂俊圆肩释属叹听摹屯邱离勒腰雄泄睛削动脉硬化血栓病理生理学动脉硬化血栓病理生理学Heeschen C,et al.N Engl J Med.2003;348:1104-1111.(with permission)Association Between Soluble CD40 Ligand Levels and the Rate of Cardiac EventsTimeDeath or Nonfatal Myocardial Infarction(%)P=.13P=.003P=.004P.001倚偿窖葡木政篷釜熄活堕溶褪讳兆行详辨汾卵么兹娄枷夹雾涤建铀减葛迄动脉硬化血栓病理生理学动脉硬化血栓病理生理学015304560750246810MonocytePlatelet Aggregates(%)Soluble CD40 Ligand(g/Liter)r=0.75P.001Level Of Soluble CD40 Ligand and MonocytePlatelet Activation in 161 Patients With Chest Pain Heeschen C,et al.N Engl J Med.2003:348:1104-1111.(with permission)梦亚番认僵敝拼贼粕嘻擎嚼伙蔷募碳赞御陕籍淳麓耳退涸疽铭翔敌德偶抓动脉硬化血栓病理生理学动脉硬化血栓病理生理学Heeschen C,et al.N Engl J Med.2003;348:1104-1111.Death or Nonfatal Myocardi