大动脉僵硬研究进展课件

UpdateonArterialStiffness大动脉僵硬研究进展 中国医学科学院阜外心血管病医院高血压诊治中心蒋雄京 DefinitionofBloodPressure Inclinicalpractice bloodpressureisdefinedintermsofsystolicanddiastolicbloodpressure whichrepresenttheextremesofthebloodpressureoscillationaroundameanvalue theMBP Infact thebloodpressurecurvemaybeconsideredasthesummationofasteadycomponent MBP andapulsatilecomponent thepulsepressure PP From O Rourke PULSEWAVE PrinciplesLeftventricleejection whichtakingbloodintotheaorta generatesapressurewavethatispropagatedtootherarteriesthroughoutthebody Propagationoccursalongthearterialwall Systole L V Blood incompressiblefluidArtery elasticconduit Radialwaveform Ascendingaorticwaveform Female18years Female48years Female97years O Rourke Nichols McDonald sBloodFlowinArteries Arnold London2005 20 BSP 300 APP 4x 0 5s 80 40 80 40 mmHg mmHg Thepulsatilecomponent PP Determinants 1 patternofleftventricularejection2 cushioningcapacityofaorta3 thetimingandintensityofwavereflections arterialstiffness PP insubjects 50yearsofage ventricularejectiontendstobereduced sothatarterialstiffnessandamplitudeandtimingofwavereflectionsbecomethemaindeterminantsofincreasedSBPandPP Question Isarterialstiffnessamarkerofcardiovasculardiseaseandmortalityintheelderly PWV ALL CAUSEMORTALITYIN1980HYPERTENSIVES 0 70 0 80 0 90 1 00 0 5 10 15 20 Follow up years Survival LowPWVtertile MediumPWVtertile HighPWVtertile Kaplan MeierP 0 0001 Laurentetal Hypertension2001 PWV PROBABILITIESOFOVERALLANDEVENT FREESURVIVALINHEMODIALYSISPATIENTS 03570105140 1 0 75 0 50 0 25 0 DurationofFollow up month 03570105140 1 0 75 0 50 0 25 0 DurationofFollow up month PWV 9 4m s PWV 12 0m s PWV 9 4m s PWV 12 0m s Probabilityofoverallsurvival Probabilityofevent freesurvival cardiovascularevents Blacheretal Circulation1999 99 2434 9 4 PWV 12 0m s 9 4 PWV 12 0m s 2 年轻人在生理条件下脉搏波速度 PWV 较慢 反射波落在升主动脉压力波的舒张期 上图 由于衰老动脉硬度不断增加 PWV加快 反射波提前产生 落在中心动脉压力波的收缩期而而主动脉舒张期压力下降 下图 DeterminantsofArterialStiffness 1 Arterialpressure2 Arterialwallstructure vascularsmoothmuscle VSM cells collagenfibers andgroundsubstance Collagengreatlymodifiesarterialrigidityandthetransitofwavereflections Neurohumoralfactors RASsystems maymodulatecollagenaccumulation Chemicalmodificationsofcollagen suchasbreakdown cross linking orglycation resultinmarkedchangesinstiffness 3 ThefunctionofendotheliumChangesinVSMtonearemodulatedbynitricoxide NO andvasoconstrictive norepinephrine angiotensin endothelin compounds whichmainlydependonthefunctionofendothelium AmplitudeofEarlierWaveReflectionsmainlybasedonthegeometry number structure andfunctionofsmallermusculararteriesandarterioleswhichserveasmajorreflectionsites 1 hypertrophyorremodelingofsmallarteriesandarterioles2 numberandbranchinganglesofarterioles3 modificationsofthemicroenvironment inparticularsodiumandothercations 4 reducedendothelium mediatedvasodilation 5 changesinmatrixcompositionofsmallarteriesandarterioles 6 geneticallymediatedalterationsofvasomotortone arisingfromsmoothmuscleorendothelialcells 动脉硬度与心血管危险 动脉硬度 反射波强度 提前 主动脉的缓冲能力 收缩压 冠状动脉灌注 左室后负荷 左室肥厚 冠状动脉缺血 心力衰竭 舒张压 脉压 搏动性压力和流量 脑与肾的微循环损害 0 0 动脉硬化如何改变大脑与肾的循环 脑 肾 其它器官 引自O RourkeMF SafarME Hypertension2005 46 200 204 血流 血流 Evaluationofarterialstiffness SurrogateMeasuresofarterialstiffness PulseWaveVelocity PulseWaveAnalysis Asimplemethodtoassessarterialstiffnessanddistensibility Widelyused Noninvasiveandreproducible Simultaneousassessmentshowsmodestcorrelation r 0 29 YasminBrownMJ QJM 1999 92 595 600 Arterialpulseandpulsewavevelocity PWV PWV Distance Pulsetransittime AugmentationIndex AI p ppAIisatimedomainestimaterofthecontributionofthereflectionsrelativetothepulsepressure ApplanationtonometryPressureRecording PulsewavefromSphygmoCorCentralaorticpressurewaveformscanbecalculatedfromtheradialarterypressurewaveformusingageneralizedtransferfunction OtherSurrogateMeasuresofstiffness AmbulatoryArterialStiffnessIndex AASI CarotidorAorticP DrelationshipAorticcharacteristicimpedanceRemaintoinvestigatefurther Othermethodsformeasuringarterialstiffness 1 Ultrasoundtechnique2 MRI3 CatheterizationWhicharecomplexandexpensive Question SBP PP PWVandAI whichisthebestandpracticalpredictorforCVrisk Somekeyquestionstoaskbeforeusingbiomarkers Circulation2006 113 2335 62 ReductioninLVmasswiththerapyin2years Numberofsubjectsrequiredwith two sided 0 05 HashimotoJ O RourkeMFetal PresentedatAHAHBPRCouncil2006 SanAntonio TX Effectsofphysiologicalphenomenaonthearterialstiffness Aging thedominantprocessalteringvascularstiffness wavereflections andPPPhysicalfitnessHeartrateBloodpressureGeneticbackground apotentialfactorofimportance NicholsWW O RourkeMF McDonald sBloodFlowinArteries 5thed London ArnoldHodder2005 PWVwithageReproducedfromAvalio etal Changeincontourandamplitudeofpressurewavesrecordedintheradialarteryandcarotidinnormalsubjectsbetweenthefirstandeighthdecadeoflife Disorderswithgreateffectsonarterialstiffness HypertensionArteriosclerosis generalizeddegenerationofmedialelementsinelasticarteriesAtherosclerosisDiabetesmellitusPrematureaorticdegenerationObesityAllthesedisordersresultinarterystiffening However tosomeextent theincreasedarterialstiffnessarereversiblebytreatment Pressure diameterrelationshipsshowschematicallyforanelasticarteryofanormalsubject left andanage matchedpatientwithhypertension right ARTERIALSTIFFNESS BODYMASSINDEXPWVisrelatedtoBMI AdaptedfromToto Moukouoetal 1986 19212325272931333537 Body massindex kg cm x10 4 21 19 17 15 13 11 9 7 Pulse wavevelocity m s Non obese Obese r 0 85 p 0 001 BMI PWVinobeseandnon obesehypertensivepatients PWVisrelatedtoglucoseintoleranceanddiabetes AdaptedfromAmaretal 0 2 4 6 8 10 Controls Glucoseintolerants Diabetics Carotid femoralPWV m s 13 14 15 No Unilateral Bilateral 13 14 15 1 2 3 4 5 PWVisrelatedtoATHEROSCLEROSISIndicators Quintilesofcarotidwallthickness Plaquesincarotidartery Carotid femoralPWV m s Carotid femoralPWV m s p 0 001 p 0 001 Valuesareadjustedforage sex meanBPandpulserate ARTERIALSTIFFNESS THERAPY TherapyforArterialStiffness Anyantihypertensivedrugthatreducesmeanarterialpressureresultsinpassivedecreaseinarterialstiffness 从病理生理上已经注意到动脉僵硬是心血管事件重要的中心环节 那么动脉僵硬度的降低是否比血压降低更重要 能独立预测心血管危险的降低 ThegoaloftreatmentforaselectiveincreaseinPP SBP TodecreaseSBPwithmaintenanceoforevenincreaseinDBP thetargetmechanismsarethedecreaseinventricularejection theactivedecreaseinarterialstiffness andthechangeinwavereflections Drugswithpotentialdirecteffectsonarterialstiffnessorwavereflection Nitroglycerin nitratederivativesNOdonors enhancersofNOproductionand orreleaseCCBACEI ARBDiureticsSpironolactoneAgentsactingoncollagencross linkingVasopeptidaseinhibitors Theeffectofnitroglycerinonwavereflection FromO Rourkeetal Quantificationofglyceryltrinitrateeffectthroughanalysisofthesynthesisedascendingaorticpressurewaveform XJJiang1 MFO Rourke3 WQJin2 LSLiu1 CWLi2 PCTai2 XCZhang2andSZLiu21HypertensionDivision FuWaiHospital ChineseAcademyofMedicalSciences PekingUnionMedicalCollege PRChina2RenMingHospital Weifang Samdong PRChina3StVincent sClinic UniversityofNewSouthWales Sydney AustraliaHeart2002 88 143 148 方法 46名志愿者 禁食 卧床 随机给予安慰剂或不同剂量的缓释GTN贴剂 0 104毫克 小时 0 208毫克 小时 0 416毫克 小时及0 625毫克 小时 记录桡动脉脉搏波并与传统的袖带血压计测量结果对照 中心动脉脉搏波通过已验证的转换函数从桡动脉脉搏波实时生成 一 用药前后传统观察指标的变化 二 用药前后中心动脉脉搏波指标变化 ChangeofCarotiddistensibilityafter6monthsoftreatment diureticsVs ACEI UnequaleffectondistensibilityforthesameBPreduction HCTZ amiloride 15 10 5 P 0 05 perindopril 20 Improvement 0 KoolMetal Jhypertes 1995 16 improvement P 0 05versusbaseline 通过脉搏波分析比较咪达普利对中心和外周动脉压的影响中国循环杂志2004 19 2 120 122 蒋雄京1张宇清1王茹2张承宗2段兵1刘力生11 中国协和医科大学中国医学科学院阜外心血管病医院高血压诊治中心 2 天津医科大学第二附属医院心内科 咪达普利治疗6周后肱动脉血压变化与中心动脉血压变化的比较 结论 咪达普利降低外周动脉压和中心动脉压均有效 且降低收缩压和脉压在中心动脉比外周动脉显著 其差异可能系波反射降低所致 SUPERIOREFFECTOFANANGIOTENSINCONVERTINGENZYMEINHIBITOROVERADIURETICFORREDUCINGAORTICSYSTOLICPRESSUREJHypertens 2007May 25 5 1095 9 Xiong JingJiang MichaelF O Rourke Yu QingZhang Xin YeHe Li ShengLiua DivisionofHypertension FuWaiHospital ChineseAcademyofMedicalSciences PekingUnionMedicalCollege Beijing100037 China b MedicalProfessorialUnit St Vincent sHospital NewSouthWalesUniversity NSW2010 Australia ChangefrombaselinetotheendoftreatmentinImdapamide n 51 andEnalapril n 50 group NODIFFERENTIALEFFECTOFFELODIPINEONCENTRALAORTICc f BRACHIALSYSTOLICPRESSUREINTONOMETERSUBSTUDYOFFEVERTRIAL XJJiang MFO Rourke LSLiu YQZhang XYHe QCCheng HLou DivisionofHypertension FuwaiHospital StVi