1、大连医科大学附属一院心内科大连医科大学附属一院心内科姜一农姜一农内内 容容内内 容容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中心动脉压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 pressureSystoleDiastol
2、eWindkessel 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 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
3、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 动脉动脉弹性弹性-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、脉压的测量内内 容容Attenuation of peripheral augmentation effect by arterial stiffnessPeripheral BP and central BPNichols WW et al. 199368 years old24 years ol
4、d50100150(mmHg)50100150(mmHg)020406080100120140160-4950-5960-6970-31493231(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
5、 hypertensionWide pulse pressureCentral hypertensionaugmentation by reflection pressure waveArterial stiffnessReduced complianceImpaired Windkessel functionMean PressurePulse PressureThe Strong Heart StudyCentral Blood Pressure Better predicts Cardiovascular Events than Does Peripheral Blood Pressur
6、e2662 patients, 63yrs, follow-up 3.4yRoman MJ, et al. AHA Sept. 2005Reflection of pressure wave as risk factorESRD patientsBlacher et al. Circulation, 19991.00.750.500.25003570105140Survival rate for cardiovascular deathTime (month)PWV9.4m/s9.4PWV12.0m/s12.0m/s PWV1.00.750.500.25003570105140Even fre
7、e 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，储备功能下降，冠状动脉灌注下降，储备功能下降， 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
8、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 coronary arteriogram1601401201008060Smulyan H et al. Ann Intern Med 20001601208016012016012080AdolescenceMiddle ag
9、eElderly500500500000015001500150Ascending 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=
10、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 BPCentral BPHyperlipidemia and central BPHypertension 43:176181, 2004Glucose intolerance and arterial stiffnessThe Ho
11、orn Study1.21.00.80.62431292566055504540120741253433323130261170188Total arterial compliance (SV/carotid PP, ml/mmHg)Transmission time from carotid artery to femoral artery (msec)Augmentation index (%)*ControlImpaired glucose toleranceType 2 DMChange in HR (bpm)-10-8-6-4-20Change in AI (%)-1.2-1-0.8
12、-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 BPDiastolic BP on brachial artery was matched for 1 yearPerindopril / indapamide (n=204)atenolol (n=202)Am J Hy
13、pertens 17:118123, 2004708090100110120130140150160170Placebo*Blood pressure (mmHg)peripheralcentral32 elderly hypertensive patients (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 studyACE inhibitorb-b
14、lockerCa channelblockerdiureticsEffect of antihypertensive drugs on AI and central BPAICentral BPdiureticsb-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
15、 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 88 248 329 369 475 406 508 278 390 126 101 1042（经校正的多因素分析）（经校正的多因素分析）内内 容容动脉血管功能改变动脉血管功能改变n中、大动脉顺应性下降n舒缩功能下降n小动脉阻力增加,顺应性下降n储备能力下降n动脉血管痉挛Metho
16、ds for Detecting Vessel DiseasenPulse contour analysis (C1，C2)nPulse Wave Velocity (PWV)nAortic pressure augmentation (reflected waves), Pulse pressurenFlow-mediated vasodilationnFlow reservenBiopsynUrinary 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应给予乙酰胆碱后出现反常的血管收缩反应血流
17、介导的血流介导的血管血管扩张扩张（FMD）测量测量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/24h内内 容容FMD(Flow mediated-dilation) 0246810
18、12“非杓型”组“杓型”组FMD（%）注：“杓型”和“非杓型”两组FMD比较，p0.001“杓型杓型”和和“非杓型非杓型”两组两组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=-0.409FMD051015202530ator10mgator20mgnormalFMD/EID(%)0周FMD4周后FMD0周EID4周后EIDp0.05p0.01血管的重要性血管的重要性VHP概念概念 将血管疾病(Vascular disease)、高血压(Hypertension)和预防(Prevention)三者
19、 作为一个整体来对待RCEUniversityNIH, MilitaryD.H.SWHOForeignAssessGrantsContractsCorporatePrivateVC$BusinessProducts Services R.O.I. Jobs Technology BaseContractsMeet National NeedsNewcoJoint VenturesNewcoPartnershipsLeadsLeadsFundsFundsSeekDiscovery“Concept”IPThioaptamersIn biodefenseDevelopmentPre-Clinical
20、Manufacture“Confirm”PlanLicenseAptaMedGLP studies Method Dev.DiagnosticsTherapeutics Make cGMP PurifyPackageRegulatoryINDtestNationalStockpileUTMB Research TeamCTD/ORTUTMB, AptaMed, Ciphergen, GE HealthcareGovernment (DARPA/NIH) $nJoint $6.3M NIAID Biodefense Proteomics Collaboratory funding nStart-up AptaMed in Galveston IncubatornNew Ciphergen Diagnostics Division in Austin to serve RegionnNew Ciphergen Satellite Facility in Galveston Incubator
