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1、中心动脉压与血管功能,1、中心动脉压机制与方法评价2、中心动脉压的意义3、血管功能指标和意义4、血管功能指标临床研究,内 容,1、中心动脉压机制与方法评价2、中心动脉压的意义3、血管功能指标和意义4、血管功能指标临床研究,内 容,动脉压相关因素,心搏量末梢阻力血管壁硬度反射波,中心动脉压,主动脉顺应性（大血管硬度）反射波 时间 幅度,London and Guerin.Am Heart J 1999;138:220-224,Normal,Decreased aortic compliance,Systole,Diastole,40%,60%,60%,50%,50%,50%,Aortic com
2、pliance and pulse pressure,Systole,Diastole,Windkessel function,大动脉顺应性降低，弹性降低，收缩压力在动脉内不能得到缓冲，使收缩压升高。舒张期大血管弹性回缩减低，使舒张压降低。结果：脉压增大,主动脉顺应性下降,Augmentation and reflection wave,Incident wave,Reflection wave,McDonalds fourth edition,Systolic BP,AugmentationIndex,Diastolic BP,Arrival of reflection wave,Arter
3、ial pressure waveform and reflection wave,反射波机制对中心动脉压的影响,脉搏波传导速度(PWV)-反射波速度 阻力微、小动脉反射位点 动脉弹性-反射波幅度 心率-反射波在收缩期叠加的幅度,AI与主动脉压、脉压的测量,1、中心动脉压机制与方法评价2、中心动脉压的意义3、血管功能指标和意义4、血管功能指标临床研究,内 容,Attenuation of peripheral augmentation effect by arterial stiffnessPeripheral BP and central BP,Nichols WW et al.1993,6
4、8 years old,24 years old,50,100,150,(mmHg),50,100,150,(mmHg),0,20,40,60,80,100,120,140,160,-49,50-59,60-69,70-,31,49,32,31,(mmHg),Reflection component,Age,Estimated aortic blood pressure,Kohara K et al.J Am Geriatr Soc,1999,Incident component,Aortic diastolic BP,Age and central blood pressure,Radial
5、 BP was matched as 150 mmHg in all age groups,Systolic hypertensionWide pulse pressure,Central hypertension,augmentation by reflection pressure wave,Arterial stiffness,Reduced complianceImpaired Windkessel function,The Great Hemodynamic Divide,Mean Pressure,Anatomy Heart,small arteries Aorta,Physiol
6、ogy Cardiac output Stiffiness Peripheral resistance,BP SBP,DBP SBP DBPEvent Risk Risk,Pulse Pressure,The Strong Heart Study,Central Blood Pressure Better predicts Cardiovascular Events than Does Peripheral Blood Pressure2662 patients,63yrs,follow-up 3.4y,Roman MJ,et al.AHA Sept.2005,The Strong Heart
7、 Study:Cox regression analyses(校正年龄、性别、体重指数、吸烟、LDL-C、DM),主动脉SBP和PP与CVD发生率独立相关，RR/10mmHg分别为1.07与1.10,p分别为0.043与0.009。进一步校正颈动脉粥样硬化病变，主动脉PP仍然与CVD显著独立相关。,Reflection of pressure wave as risk factorESRD patients,Blacher et al.Circulation,1999,1.0,0.75,0.50,0.25,0,0,35,70,105,140,Survival rate for cardiova
8、scular death,Time(month),PWV9.4m/s,9.4PWV12.0m/s,12.0m/s PWV,1.0,0.75,0.50,0.25,0,0,35,70,105,140,Even free rate for cardiovascular accidents,Time(month),Augmentation index 1 群,Augmentation index 2 群,Augmentation index 3 群,Augmentation index 4 群,London GM et al.Hypertension,2001,中心动脉压和脉压升高对心血管系统影响,左
9、室后负荷增加，左室重构 冠状动脉灌注下降，储备功能下降，心肌缺血 内皮损伤和功能紊乱，动脉硬化性疾病 进展,Circulation 2004;109:184-189,NO lesions,1211109876543,Augmented pressure mmHg,Onevessel,Twovessels,Three vessels,AI and coronary heart diseaseAssociation between aortic AI and coronary arteriogram,160,140,120,100,80,60,Smulyan H et al.Ann Intern
10、Med 2000,160,120,80,160,120,160,120,80,Adolescence,Middle age,Elderly,500,500,500,0,0,0,0,150,0,150,0,150,Ascending Aortic BP(mmHg),Ascending Aortic blood flow(ml/s),Coronary blood flow(ml/min),80,McDonalds fourth edition,Blood pressure(mmHg),吸烟对中心动脉压和周围动脉压的影响,50,60,70,80,90,100,110,120,130,140,-8,-
11、7,-6,-5,-4,-3,-2,-1,0,1,2,Aortic AI(%),*,Brachial BP,Aortic BP,*,*p0.05,Non-smoker(n=116)Smokers(n=41),Hypertension.2003;41:183-187,J Am Coll Cardiol 2002;39:1005,160150140130120110100908070,Control subjects(n=68),Hyperlipidemia(n=68),0.01,*,Blood pressure(mmHg),Peripheral BPCentral BP,Hyperlipidemi
12、a and central BP,Hypertension 43:176181,2004,Glucose intolerance and arterial stiffnessThe Hoorn Study,1.21.00.80.6,243,129,256,6055504540,120,74,125,3433323130,261,170,188,Total arterial compliance(SV/carotid PP,ml/mmHg),Transmission time from carotid artery to femoral artery(msec),Augmentation ind
13、ex(%),*,*,*,*,ControlImpaired glucose toleranceType 2 DM,Change in HR(bpm),-10,-8,-6,-4,-2,0,Change in AI(%),-1.2,-1,-0.8,-0.6,-0.4,-0.2,0,Change in PWV(m/sec),-5,-4,-3,-2,-1,0,1,2,3,4,Asmar RG,et al.Hypertension.2001;38:922,*,*,MeanSD.*p0.05,*p0.001 vs atenolol.,Effect of antihypertensive drugs on
14、brachial BP and central BP,Diastolic BP on brachial artery was matched for 1 year,Perindopril/indapamide(n=204),atenolol(n=202),Am J Hypertens 17:118123,2004,70,80,90,100,110,120,130,140,150,160,170,Placebo,*,*,*,*,*,*,*,*,*,*,*,*,Blood pressure(mmHg),peripheralcentral,32 elderly hypertensive patien
15、ts(age 65-80)were treated for 4 weeks each drugs in double blind and cross-over fashion.,Effect of antihypertensive drugsdouble blind and cross-over study,ACE inhibitor,b-blocker,Ca channelblocker,diuretics,Effect of antihypertensive drugs on AI and central BP,AICentral BPdiureticsb-blockerACE inhib
16、itor/ARBCa channel blocker,CAF:肱动脉和中心动脉收缩压,CAF:血压对终点事件的影响（未校正的多因素分析）,（经校正的多因素分析）,GREAT DEBATES IN HYPERTENSION:2007ACC,Antihypertensive Therapy Should be Tailored to Measures of Arterial Stiffness Still not enough data to make this assertion.However,there is need to develop such data.,1、中心动脉压机制与方法评价
17、2、中心动脉压的意义3、血管功能指标和意义4、血管功能指标临床研究,内 容,动脉血管功能改变,中、大动脉顺应性下降舒缩功能下降小动脉阻力增加,顺应性下降储备能力下降动脉血管痉挛,Methods for Detecting Vessel Disease,Pulse contour analysis(C1，C2)Pulse Wave Velocity(PWV)Aortic pressure augmentation(reflected waves),Pulse pressureFlow-mediated vasodilationFlow reserveBiopsyUrinary protein e
18、xcretion,乙酰胆碱试验,在基线期无严重的梗阻性缺损,给予乙酰胆碱后出现反常的血管收缩反应,血流介导的血管扩张（FMD）测量,血管舒张,非内皮依赖性舒张功能(endothelium-independentdilatation,EID),内皮依赖性舒张功能(endothelium-dependent dilation,EDD),药物:乙酰胆碱,生理性刺激:反应性充血,FMD,硝普钠、硝酸甘油等,内皮由来NO,外源NO,动脉血管舒张功能,Survival without ischemic heart disease in hypertensive patients with MA or no
19、rmoalbuminuria(MONICA study),0,1,2,3,4,5,6,7,8,9,10,years,(Jensen et al:Hypertension,2000),75,80,85,90,95,100,70,Proportion without ischemic heart disease(%),P0.003,30mg/24h,30mg/24h,1、中心动脉压机制与方法评价2、中心动脉压的意义3、血管功能指标和意义4、血管功能指标临床研究 我们的工作,内 容,24小时动态血压与动脉内皮功能相关性的研究,“非杓型”原发性高血压患者靶器官的损伤远较“杓型”患者严重，心脑血管事件的
20、发生率更高。动脉内皮功能的变化？原发性高血压患者46名，“杓型”31名，“非杓型”15名 测定FMD(Flow mediated-dilation),0,2,4,6,8,10,12,“非杓型”组,“杓型”组,FMD（%）,注：“杓型”和“非杓型”两组FMD比较，p0.001,“杓型”和“非杓型”两组FMD比较,FMD与24hSBP的相关性,r=-0.438,FMD,FMD与年龄的相关性,r=-0.409,FMD,阿托伐他汀对血脂正常高血压患者血管内皮功能的影响,高血压病患者早期即有血管内皮功能失调。他汀类药物对血脂正常高血压患者是否改善血管内皮功能？与剂量的关系？,0,5,10,15,20,2
21、5,30,ator10mg,ator20mg,normal,FMD/EID(%),0周FMD,4周后FMD,0周EID,4周后EID,阿托伐他汀对血脂正常高血压患者FMD/EID影响,结 论,高血压病患者内皮功能失调表现为以内皮依赖性血管舒张反应减弱为特征。阿托伐他汀能改善血脂正常高血压患者血管内皮功能，可能具有剂量依赖性。,小 结,中心动脉压与脉压相关密切；与心血管事件相关性好；不同降压药对周围血压和中心动脉压降低不同，对评价不同降压药物作用有一定意义。动脉功能评价方法多，不同侧面反映血管功能。有一定临床应用价值。,谢 谢,血管的重要性VHP概念,Vascular diseaseHypert
22、ensionPrevention 将血管疾病(Vascular disease)、高血压(Hypertension)和预防(Prevention)三者 作为一个整体来对待,讨论,高血压病患者表现为以内皮依赖性血管舒张反应减弱为特征的内皮功能失调 阿托伐他汀对内皮的保护功能非常明显，而且发生的非常早，独立于患者的脂质水平而存在，且可能剂量越大，患者的获益越大,结 论,“非杓型”原发性高血压患者较“杓型”的动脉 内皮功能损伤重;年龄、血清总胆固醇、24小时平均收缩压是 影响动脉内皮功能变化的独立危险因素。,Center for Research Translation,RCEUniversity,
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24、hioaptamersIn biodefense,Development,Pre-Clinical,Manufacture,“Confirm”PlanLicenseAptaMed,GLP studies Method Dev.DiagnosticsTherapeutics,Make cGMP PurifyPackageRegulatory,INDtest,NationalStockpile,UTMB Research Team,CTD/ORT,UTMB,AptaMed,Ciphergen,GE Healthcare,Government(DARPA/NIH),$,Partnership:UTM
25、B,AptaMed,and Ciphergen,Joint$6.3M NIAID Biodefense Proteomics Collaboratory funding Start-up AptaMed in Galveston Incubator New Ciphergen Diagnostics Division in Austin to serve RegionNew Ciphergen Satellite Facility in Galveston Incubator,Conclusions,The bioterrorism threat is realThe time for action is nowPreparedness can serve as a deterrentUTMB and the Gulf Coast are at the forefront of anti-bioterrorism and emerging diseases researchVision:new biodefense industry is developing-we can lead this effortCatalyst for biotechnology industry and jobs,谢谢！,
