中心動脈壓與血管功能

1、中心動脈壓與血管功能,,1、中心動脈壓機制與方法評價2、中心動脈壓的意義3、血管功能指標和意義4、血管功能指標臨床研究,內(nèi) 容,1、中心動脈壓機制與方法評價2、中心動脈壓的意義3、血管功能指標和意義4、血管功能指標臨床研究,內(nèi) 容,動脈壓相關因素,心搏量末梢阻力血管壁硬度反射波,中心動脈壓,主動脈順應性（大血管硬度）反射波 時間 幅度,London and Guerin. Am Hear

2、t J 1999;138:220-224,Normal,Decreased aortic compliance,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Systole,Diastole,40%,60%,60%,50%,50%,50%,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Aortic compliance and pulse pressure,

3、Systole,Diastole,Windkessel function,大動脈順應性降低，彈性降低，收縮壓力在動脈內(nèi)不能得到緩沖，使收縮壓升高。舒張期大血管彈性回縮減低，使舒張壓降低。結果：脈壓增大,主動脈順應性下降,,Augmentation and reflection wave,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Incident

4、wave,Reflection wave,McDonald’s fourth edition,,Systolic BP,,AugmentationIndex,,,Diastolic BP,,,,,Arrival of reflection wave,Arterial pressure waveform and reflection wave,反射波機制對中心動脈壓的影響,脈搏波傳導速度(PWV) --反射波速度 阻力微、小動脈—反射

5、位點 動脈彈性--反射波幅度? 心率--反射波在收縮期疊加的幅度,AI與主動脈壓、脈壓的測量,1、中心動脈壓機制與方法評價2、中心動脈壓的意義3、血管功能指標和意義4、血管功能指標臨床研究,內(nèi) 容,Attenuation of peripheral augmentation effect by arterial stiffnessPeripheral BP and central BP,Nichols WW et al.

6、 1993,,,,,,,,,,,,,,,,,,68 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,E

7、stimated aortic blood pressure,Kohara K et al. J Am Geriatr Soc, 1999,Incident component,,Aortic diastolic BP,,Age and central blood pressure,,,,,Radial BP was matched as 150 mmHg in all age groups,Systolic hypertension

8、Wide pulse pressure,Central hypertension,augmentation by reflection pressure wave,Arterial stiffness,Reduced complianceImpaired Windkessel function,,,,,The Great Hemodynamic Divide,,,Mean Pressure,Anatomy Heart, s

9、mall arteries Aorta,Physiology ↑ Cardiac output ↑ Stiffiness ↑ Peripheral resistance,BP ↑ SBP ,↑ DBP ↑ SBP ↓ DBPEvent ↑Risk

10、 ↑↑↑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

11、 Sept. 2005,The Strong Heart Study: Cox regression analyses(校正年齡、性別、體重指數(shù)、吸煙、LDL-C、DM),主動脈SBP和PP與CVD發(fā)生率獨立相關，RR/10mmHg分別為1.07與1.10, p分別為0.043與0.009。進一步校正頸動脈粥樣硬化病變，主動脈PP仍然與CVD顯著獨立相關。,Reflection of pressure wave as risk f

12、actorESRD patients,Blacher et al. Circulation, 1999,1.0,0.75,0.50,0.25,0,0,35,70,105,140,Survival rate for cardiovascular death,Time (month),,,,PWV<9.4m/s,9.4≦PWV≦12.0m/s,12.0m/s <PWV,,,,,,,,,,,1.0,0.75,0.50,0.25,

13、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,中心動脈壓和脈壓升高對心

14、血管系統(tǒng)影響,左室后負荷增加，左室重構 冠狀動脈灌注下降，儲備功能下降， 心肌缺血 內(nèi)皮損傷和功能紊亂，動脈硬化性疾病 進展,Circulation 2004;109:184-189,NO lesions,,,,,,,,,,1211109876543,Augmented pressure mmHg,Onevessel,Twovessels,Three vessels,,,,,,,AI and c

15、oronary heart diseaseAssociation between aortic AI and coronary arteriogram,,,,,,,,,,,,,,160,140,120,100,80,60,Smulyan H et al. Ann Intern Med 2000,,,,,,,,160,120,80,160,120,160,120,80,Adolescence,Middle age,Elderly,,,,

16、,,,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,McDonald’s fourth edition,,,Blood pressure (mmHg),吸煙對中心動脈壓和周圍動脈壓的影響,,,,,,,,,,,

17、,,,50,60,70,80,90,100,110,120,130,140,,,,,,,,,,,,,,,,,,-8,-7,-6,-5,-4,-3,-2,-1,0,1,2,Aortic AI (%),*,,,,Brachial BP,Aortic BP,*,* p<0.05,,,Non-smoker (n=116)Smokers (n=41),Hypertension. 2003;41:183-187,,,J Am Coll Ca

18、rdiol 2002;39:1005,,,,,,,,,,,,,160150140130120110100908070,,Control subjects(n=68),Hyperlipidemia(n=68),0.01,,*,Blood pressure (mmHg),,,Peripheral BPCentral BP,,,,,Hyperlipidemia and central BP,Hypertension

19、43:176–181, 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,

20、 ml/mmHg),Transmission time from carotid artery to femoral artery (msec),Augmentation index (%),*,*,*,*,,,,ControlImpaired glucose toleranceType 2 DM,Change in HR (bpm),,,,,,,-10,-8,-6,-4,-2,0,,,Change in AI (%),,,,,

21、,,,,,-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,,,*,**,Mean±SD. *p<0.05, ** p<0.001 vs atenolol.,Effect of antihypert

22、ensive drugs on 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 17:118–123, 2004,,,,,,,,,,,,,,,,,,,,,,,70,80,90,100,110,

23、120,130,140,150,160,170,,Placebo,*,*,*,*,*,*,*,,,,,,*,*,*,*,*,Blood pressure (mmHg),,,peripheralcentral,32 elderly hypertensive patients (age 65-80) were treated for 4 weeks each drugs in double blind and cross-over fa

24、shion.,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 BPdiuretics↓→↓b-bloc

25、ker↑→↓→ACE inhibitor/ARB↓↓↓Ca channel blocker↓↓↓,,,,CAFÉ: 肱動脈和中心動脈收縮壓,CAFÉ: 血壓對終點事件的影響（未校正的多因素分析）,（經(jīng)校正的多因素分析）,GREAT DEBATES IN HYPERTENSION:2007ACC,Antihypertensive Therapy Should be Tailored to Mea

26、sures of Arterial Stiffness Still not enough data to make this assertion. However, there is need to develop such data.,1、中心動脈壓機制與方法評價2、中心動脈壓的意義3、血管功能指標和意義4、血管功能指標臨床研究,內(nèi) 容,動脈血管功能改變,中、大動脈順應性下降舒縮功能下降小動脈阻力增加,順應

27、性下降儲備能力下降動脈血管痙攣,Methods for Detecting Vessel Disease,Pulse contour analysis (C1，C2)Pulse Wave Velocity (PWV)Aortic pressure augmentation (reflected waves), Pulse pressureFlow-mediated vasodilationFlow reserveBio

28、psyUrinary protein excretion,,乙酰膽堿試驗,在基線期無嚴重的梗阻性缺損,給予乙酰膽堿后出現(xiàn)反常的血管收縮反應,,血流介導的血管擴張（FMD）測量,血管舒張,,,,,非內(nèi)皮依賴性舒張功能 (endothelium-independentdilatation, EID),內(nèi)皮依賴性舒張功能(endothelium-dependent dilation, EDD),,藥物:乙酰膽堿,生理性刺激:反應

29、性充血,FMD,硝普鈉、硝酸甘油等,內(nèi)皮由來NO,外源NO,動脈血管舒張功能,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Survival without ischemic heart disease in hypertensive patients with MA or normoalbuminuria (MONICA study),0,1,2,3,

30、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 (%),P<0.003,>30mg/24h,<30mg/24h,,1、中心動脈壓機制與方法評價2、中心動脈壓的意義3、血管功能指標和意義4、血管功能指標臨床研究

31、 —— 我們的工作,內(nèi) 容,24小時動態(tài)血壓與動脈內(nèi)皮功能相關性的研究,“非杓型”原發(fā)性高血壓患者靶器官的損傷遠較 “杓型”患者嚴重，心腦血管事件的發(fā)生率更高。動脈內(nèi)皮功能的變化？ 原發(fā)性高血壓患者46名，“杓型”31名，“非杓型”15名 測定FMD(Flow mediated-dilation),,,,,,,,,,,,,,,,0,2,4,6,8,10,12,“非杓型”組,“杓型”組,FMD（%）,注：“

32、杓型”和“非杓型”兩組FMD比較，p<0.001,“杓型”和“非杓型”兩組FMD比較,,,FMD與24hSBP的相關性,r=-0.438,FMD,,,FMD與年齡的相關性,r=-0.409,FMD,阿托伐他汀對血脂正常高血壓患者血管內(nèi)皮功能的影響,,高血壓病患者早期即有血管內(nèi)皮功能失調(diào)。他汀類藥物對血脂正常高血壓患者是否改善血管內(nèi)皮功能？與劑量的關系？,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

33、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,5,10,15,20,25,30,ator10mg,ator20mg,normal,FMD/EID(%),,,0周FMD,,,4周后FMD,,,0周EID,,4周后EID,阿托伐他汀對血脂正常高血壓患者FMD/ EID影響,,結 論,高血壓病患者內(nèi)皮功能失調(diào)表現(xiàn)為以內(nèi)皮依賴性血管舒張反應減弱為特征。阿托伐他汀能改善血脂正常高血壓患者

34、血管內(nèi)皮功能，可能具有劑量依賴性。,小 結,中心動脈壓與脈壓相關密切；與心血管事件相關性好；不同降壓藥對周圍血壓和中心動脈壓降低不同，對評價不同降壓藥物作用有一定意義。動脈功能評價方法多，不同側面反映血管功能。有一定臨床應用價值。,謝 謝,,血管的重要性——VHP概念,Vascular diseaseHypertensionPrevention 將血管疾病(Vascular disease)、高血壓(Hyp

35、ertension)和預防(Prevention)三者 作為一個整體來對待,討論,高血壓病患者表現(xiàn)為以內(nèi)皮依賴性血管舒張反應減弱為特征的內(nèi)皮功能失調(diào) 阿托伐他汀對內(nèi)皮的保護功能非常明顯，而且發(fā)生的非常早，獨立于患者的脂質(zhì)水平而存在，且可能劑量越大，患者的獲益越大,結 論,,“非杓型”原發(fā)性高血壓患者較“杓型”的動脈 內(nèi)皮功能損傷重;年齡、血清總膽固醇、 24小時平均收縮壓是 影響動脈內(nèi)皮功能變化的獨立危

36、險因素。,Center for Research Translation,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,RCEUniversity,NIH, MilitaryD.H.SWHOForeign,Assess,GrantsContracts,CorporatePrivateVC,$$$$,Business,,,,Products Services R.O.I. Jobs Techno

37、logy Base,ContractsMeet National Needs,Newco,Joint Ventures,Newco,Partnerships,Leads,Leads,Funds,Funds,Seek,,,Example: UTMB, AptaMed, Ciphergen, DowPharma and GE Healthcare,,,Discovery,“Concept”IPThioaptamersIn biode

38、fense,,,,Development,Pre-Clinical,Manufacture,“Confirm”PlanLicenseAptaMed,GLP studies Method Dev.DiagnosticsTherapeutics,Make cGMP PurifyPackageRegulatory,INDtest,,NationalStockpile,UTMB Research Team,CTD/ORT

39、,UTMB, AptaMed, Ciphergen, GE Healthcare,,,Government (DARPA/NIH…),$$$,,,Partnership: UTMB, AptaMed, and Ciphergen,Joint $6.3M NIAID Biodefense Proteomics Collaboratory funding Start-up AptaMed in Galveston In

40、cubator 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

41、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