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1、中心动脉压与血管功能中心动脉压与血管功能动脉压动脉压相关因素相关因素心搏量心搏量末梢阻力末梢阻力血管壁硬度血管壁硬度反射波反射波中心动脉压中心动脉压主动脉顺应性大血管硬度主动脉顺应性大血管硬度反射波反射波 时间时间 幅度幅度London and Guerin. Am Heart J 1999;138:220-224NormalDecreased aortic complianceSystoleDiastole40%60%60%50%50%50%Aortic compliance and pulse pressureSystoleDiastoleWindkessel function大动脉顺应性
2、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 waveIncident waveReflection waveMcDonalds fourth editionSystolic BPAugmentationIndex Diastolic BPArrival of reflection waveArterial pressure waveform and reflection wave反射波机制对中心动脉压的影响反射波机制对中心动脉压的影响 脉搏波传导速度脉搏
3、波传导速度(PWV) -(PWV) -反射波速度反射波速度 阻力微、小动脉阻力微、小动脉反射位点反射位点 动脉弹性动脉弹性-反射波幅度反射波幅度 心率心率-反射波在收缩期叠加的幅度反射波在收缩期叠加的幅度 AI与主动脉压、脉压的测量与主动脉压、脉压的测量Attenuation of peripheral augmentation effect by arterial stiffnessPeripheral BP and central BPNichols WW et al. 199368 years old24 years old50100150(mmHg)50100150(mmHg)0204
4、06080100120140160-4950-5960-6970-31493231(mmHg)Reflection component AgeEstimated aortic blood pressureKohara K et al. J Am Geriatr Soc, 1999Incident component Aortic diastolic BPAge and central blood pressureRadial BP was matched as 150 mmHg in all age groupsSystolic hypertensionWide pulse pressureC
5、entral hypertensionaugmentation by reflection pressure waveArterial stiffnessReduced complianceImpaired Windkessel functionThe Great Hemodynamic DivideMean PressureAnatomy Heart, small arteries AortaPhysiology Cardiac output Stiffiness Peripheral resistanceBP SBP , DBP SBP DBPEvent Risk RiskPulse Pr
6、essureThe Strong Heart StudyCentral Blood Pressure Better predicts Cardiovascular Events than Does Peripheral Blood Pressure2662 patients, 63yrs, follow-up 3.4yRoman MJ, et al. AHA Sept. 2005The Strong Heart Study: Cox regression analyses(校正年龄、性别、体重指数、吸烟、校正年龄、性别、体重指数、吸烟、LDL-CLDL-C、DMDM) )n n主动脉主动脉SB
7、PSBP和和PPPP与与CVDCVD发生率独立相关，发生率独立相关，RR/10mmHgRR/10mmHg分别为分别为1.071.07与与1.10, p1.10, p分别为分别为0.0430.043与与0.0090.009。n n进一步校正颈动脉粥样硬化病变，主动脉进一步校正颈动脉粥样硬化病变，主动脉PPPP仍然与仍然与CVDCVD显著独立相关。显著独立相关。Reflection of pressure wave as risk factorESRD patientsBlacher et al. Circulation, 19991.00.750.500.25003570105140Surviv
8、al rate for cardiovascular deathTime (month)PWV9.4m/s9.4PWV12.0m/s12.0m/s PWV1.00.750.500.25003570105140Even free rate for cardiovascular accidentsTime (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中心动
9、脉压和脉压升高对心血管系统影响心血管系统影响 左室后负荷增加，左室重构左室后负荷增加，左室重构 冠状动脉灌注下降，储藏功能下降，冠状动脉灌注下降，储藏功能下降， 心肌缺血心肌缺血 内皮损伤和功能紊乱，动脉硬化性疾病内皮损伤和功能紊乱，动脉硬化性疾病 进展进展Circulation 2004;109:184-189NO lesions1211109876543Augmented pressure mmHgOnevesselTwovesselsThree vesselsAI and coronary heart diseaseAssociation between aortic AI and co
10、ronary arteriogram1601401201008060Smulyan H et al. Ann Intern Med 20001601208016012016012080AdolescenceMiddle ageElderly500500500000015001500150Ascending Aortic BP (mmHg)Ascending Aortic blood flow (ml/s)Coronary blood flow (ml/min)80McDonalds fourth editionBlood pressure (mmHg)吸烟对中心动脉压和周围动脉压的影响吸烟对中
11、心动脉压和周围动脉压的影响5060708090100110120130140-8-7-6-5-4-3-2-1012Aortic AI (%)*Brachial BPAortic BP* p0.05Non-smoker (n=116)Smokers (n=41)Hypertension. 2003;41:183-187J Am Coll Cardiol 2002;39:1005160150140130120110100908070Control subjects(n=68)Hyperlipidemia(n=68)0.01*Blood pressure (mmHg)Peripheral BPCen
12、tral BPHyperlipidemia and central BPHypertension 43:176181, 2004Glucose intolerance and arterial stiffnessThe Hoorn Study1.21.00.80.62431292566055504540120741253433323130261170188Total arterial compliance (SV/carotid PP, ml/mmHg)Transmission time from carotid artery to femoral artery (msec)Augmentat
13、ion index (%)*ControlImpaired glucose toleranceType 2 DMChange in HR (bpm)-10-8-6-4-20Change in AI (%)-1.2-1-0.8-0.6-0.4-0.20Change in PWV (m/sec)-5-4-3-2-101234Asmar RG, et al. Hypertension. 2001;38:922*MeanSD. *p0.05, * p0.001 vs atenolol.Effect of antihypertensive drugs on brachial BP and central
14、 BPDiastolic BP on brachial artery was matched for 1 yearPerindopril / indapamide (n=204)atenolol (n=202)Am J Hypertens 17:118123, 2004708090100110120130140150160170Placebo*Blood pressure (mmHg)peripheralcentral32 elderly hypertensive patients (age 65-80) were treated for 4 weeks each drugs in doubl
15、e blind and cross-over fashion.Effect of antihypertensive drugsdouble blind and cross-over studyACE inhibitorb-blockerCa channelblockerdiureticsEffect of antihypertensive drugs on AI and central BPAICentral BP diureticsb-blockerACE inhibitor/ARBCa channel blockerCAF: 肱动脉和中心动脉肱动脉和中心动脉收缩压收缩压肱动脉收缩压肱动脉收
16、缩压平均差异平均差异(AUC)=0.7mmHg(AUC)=0.7mmHg133.9133.2氨氯地平氨氯地平阿替洛尔阿替洛尔P=.07125.5121.2P.0001 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 AUC115140135130125120mm Hg中心动脉收缩压中心动脉收缩压平均差异平均差异(AUC)=4.3mmHg(AUC)=4.3mmHg时间时间( (年年) )阿替洛尔阿替洛尔 86 243 324 356 445 372 462 270 339 128 85 1031氨氯地平氨氯地平 88 248 329 369 475 406 508 2
17、78 390 126 101 1042CAF: 血压对终点事件的影响血压对终点事件的影响未校正的多因素分析未校正的多因素分析X X X X2 2 2 2P P P P值值值值HRHRHRHRCICICICI肱动脉脉压的肱动脉脉压的肱动脉脉压的肱动脉脉压的差值差值差值差值21.021.021.021.00.00010.00010.00010.00011.211.211.211.211.12-1.301.12-1.301.12-1.301.12-1.30中心动脉脉压中心动脉脉压中心动脉脉压中心动脉脉压的差值的差值的差值的差值17.817.817.817.80.00010.00010.00010.0
18、0011.201.201.201.201.11-1.301.11-1.301.11-1.301.11-1.30中心动脉压中心动脉压中心动脉压中心动脉压增强指数增强指数增强指数增强指数7.107.107.107.100.0080.0080.0080.0081.221.221.221.221.06-1.401.06-1.401.06-1.401.06-1.40P1P1P1P119.019.019.019.00.00010.00010.00010.00011.371.371.371.371.20-1.541.20-1.541.20-1.541.20-1.54 X X X X2 2 2 2 P P P
19、 P值值值值 HR HR HR HRCICICICI 中心动脉脉中心动脉脉中心动脉脉中心动脉脉压压压压 的差值的差值的差值的差值 3.91 3.91 3.91 3.91 0.048 0.048 0.048 0.048 1.11 1.11 1.11 1.111.00-1.211.00-1.211.00-1.211.00-1.21经校正的多因素分析经校正的多因素分析GREAT DEBATES IN HYPERTENSION:2007ACCn nAntihypertensive Therapy Should be Tailored to Measures of Arterial Stiffness
20、Still not enough data to make this assertion. However, there is need to develop such data.动脉血管功能改变动脉血管功能改变n n中、大动脉顺应性下降n n舒缩功能下降n n小动脉阻力增加,顺应性下降n n储藏能力下降n n动脉血管痉挛Methods for Detecting Vessel Diseasen nPulse contour analysis (C1，C2)n nPulse Wave Velocity (PWV)n nAortic pressure augmentation (reflecte
21、d waves), Pulse pressuren nFlow-mediated vasodilationn nFlow reserven nBiopsyn nUrinary protein excretion乙酰胆碱乙酰胆碱试验试验在基线期无严重的梗阻性缺损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响给予乙酰胆碱后出现反常的血管收缩反响血流介导的血管扩张血流介导的血管扩张FMD测量测量血管舒张血管舒张非内皮依赖性舒张功能非内皮依赖性舒张功能非内皮依赖性舒张功能非内皮依赖性舒张功能 ( (endothelium-independentendothelium-independe
22、ntdilatation, EID)dilatation, EID)内皮依赖性舒张功能内皮依赖性舒张功能内皮依赖性舒张功能内皮依赖性舒张功能( (endothelium-endothelium-dependent dependent dilation, EDD)dilation, EDD)药物药物药物药物: : : :乙酰胆碱乙酰胆碱乙酰胆碱乙酰胆碱生理性刺激生理性刺激生理性刺激生理性刺激: : : :反响性充血反响性充血反响性充血反响性充血,FMD,FMD,FMD,FMD硝普钠、硝普钠、硝普钠、硝普钠、硝酸甘油等硝酸甘油等硝酸甘油等硝酸甘油等内皮由来内皮由来内皮由来内皮由来NONONONO外
23、源外源外源外源NONONONO动脉血管舒张功能动脉血管舒张功能Survival without ischemic heart disease in hypertensive patients with MA or normoalbuminuria (MONICA study)012345678910years(Jensen et al: Hypertension, 2000)758085909510070Proportion without ischemic heart disease (%)P30mg/24h30mg/24h24小时动态血压与动脉内皮功能相关性的研究 n n “ “ “ “非
24、杓型原发性高血压患者靶器官的损伤非杓型原发性高血压患者靶器官的损伤非杓型原发性高血压患者靶器官的损伤非杓型原发性高血压患者靶器官的损伤远较远较远较远较 “ “ “ “杓型患者严重，心脑血管事件的发杓型患者严重，心脑血管事件的发杓型患者严重，心脑血管事件的发杓型患者严重，心脑血管事件的发生率更高。动脉内皮功能的变化？生率更高。动脉内皮功能的变化？生率更高。动脉内皮功能的变化？生率更高。动脉内皮功能的变化？n n 原发性高血压患者原发性高血压患者原发性高血压患者原发性高血压患者46464646名，名，名，名，“杓型杓型杓型杓型31313131名，名，名，名，“非杓型非杓型非杓型非杓型1515151
25、5名名名名n n 测定测定测定测定FMD(Flow mediated-dilation)FMD(Flow mediated-dilation)FMD(Flow mediated-dilation)FMD(Flow mediated-dilation) 024681012“非杓型组“杓型组FMD%注：“杓型和“非杓型两组FMD比较，p0.001“杓型和杓型和“非杓型两组非杓型两组FMD比较比较FMD与与24hSBP的相关性的相关性r=-0.438r=-0.438FMDFMD与年龄的相关性与年龄的相关性r=-0.409r=-0.409FMD阿托伐他汀对血脂正常高血压患者血管内皮功能的影响n n高血
26、压病患者早期即有血管内皮功能失调。高血压病患者早期即有血管内皮功能失调。高血压病患者早期即有血管内皮功能失调。高血压病患者早期即有血管内皮功能失调。n n他他他他汀汀汀汀类类类类药药药药物物物物对对对对血血血血脂脂脂脂正正正正常常常常高高高高血血血血压压压压患患患患者者者者是是是是否否否否改改改改善善善善血管内皮功能？与剂量的关系？血管内皮功能？与剂量的关系？血管内皮功能？与剂量的关系？血管内皮功能？与剂量的关系？051015202530ator10mgator20mgnormalFMD/EID(%)0周FMD4周后FMD0周EID4周后EID阿托伐他汀对血脂正常高血压患者FMD/ EID影响
27、p0.05p0.01结 论n n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响减弱为特征。n n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。小小 结结n n中心动脉压与脉压相关密切；与心血管事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心动脉压降低不同，对评价不同降压药物作用有一定意义。作用有一定意义。n n动脉功能评价方法多，不同侧面反映血管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。功能。有一定临床应用价值。谢谢 谢谢血管的重要性血管的重要性
28、VHP概念概念Vascular diseaseHypertensionPrevention 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n n高血压病患者表现为以内皮依赖性血管舒张反响高血压病患者表现为以内皮依赖性血管舒张反响高血压病患者表现为以内皮依赖性血管舒张反响高血压病患者表现为以内皮依赖性血管舒张反响减弱为特征的内皮功能失调减弱为特征的内皮功能失调减弱为特征的内皮功能失调减弱为特征的内皮功能失调 n n阿托伐他汀对内皮的保护功能非常明显，而且发阿托伐他汀对内皮的保护功能非常明显，而且发阿托伐
29、他汀对内皮的保护功能非常明显，而且发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，且生的非常早，独立于患者的脂质水平而存在，且生的非常早，独立于患者的脂质水平而存在，且生的非常早，独立于患者的脂质水平而存在，且可能剂量越大，患者的获益越大可能剂量越大，患者的获益越大可能剂量越大，患者的获益越大可能剂量越大，患者的获益越大 结结 论论q “ “非杓型原发性高血压患者较非杓型原发性高血压患者较非杓型原发性高血压患者较非杓型原发性高血压患者较“ “杓型的动杓型的动杓型的动杓型的动脉脉脉脉q 内皮功能损伤重内皮功能损伤重内皮功能损伤重内皮功能损伤重; ;q年龄、血清
30、总胆固醇、年龄、血清总胆固醇、年龄、血清总胆固醇、年龄、血清总胆固醇、 24 24小时平均收缩压是小时平均收缩压是小时平均收缩压是小时平均收缩压是q 影响动脉内皮功能变化的独立危险因素。影响动脉内皮功能变化的独立危险因素。影响动脉内皮功能变化的独立危险因素。影响动脉内皮功能变化的独立危险因素。Center for Research TranslationRCEUniversityNIH, MilitaryWHOForeignAssessGrantsContractsCorporatePrivateVC$BusinessProducts Services R.O.I. Jobs Technolo
31、gy BaseContractsMeet National NeedsNewcoJoint VenturesNewcoPartnershipsLeadsLeadsFundsFundsSeekExample: UTMB, AptaMed, Ciphergen, DowPharma and GE HealthcareDiscovery“ConceptIPThioaptamersIn biodefenseDevelopmentPre-ClinicalManufacture“ConfirmPlanLicenseAptaMedGLP studies Method Dev.DiagnosticsThera
32、peutics Make cGMP PurifyPackageRegulatoryINDtestNationalStockpileUTMB Research TeamCTD/ORTUTMB, AptaMed, Ciphergen, GE HealthcareGovernment (DARPA/NIH) $Partnership: UTMB, AptaMed, and Ciphergen n nJoint $6.3M NIAID Biodefense Joint $6.3M NIAID Biodefense Proteomics Collaboratory funding Proteomics
33、Collaboratory funding n nStart-up AptaMed in Galveston Start-up AptaMed in Galveston Incubator Incubator n nNew Ciphergen Diagnostics Division New Ciphergen Diagnostics Division in Austin to serve Region in Austin to serve Regionn nNew Ciphergen SatelliteNew Ciphergen Satellite Facility in Galveston
34、 Incubator Facility in Galveston Incubator Conclusionsn nThe bioterrorism threat is realThe bioterrorism threat is realn nThe time for action is nowThe time for action is nown nPreparedness can serve as a deterrentPreparedness can serve as a deterrentn nUTMB and the Gulf Coast are at the forefront o
35、f UTMB and the Gulf Coast are at the forefront of anti-bioterrorism and emerging diseases researchanti-bioterrorism and emerging diseases researchn nVision: new biodefense industry is developing - Vision: new biodefense industry is developing - we can lead this effortwe can lead this effortn nCatalyst for biotechnology industry and jobsCatalyst for biotechnology industry and jobs
