难治性高血压

Objective

Expandingourunderstandingofthecausesofresistanthypertensionandtherebypotentiallyallowingformoreeffectivepreventionand/ortreatmentwillbeessentialtoimprovethelong-termclinicalmanagementofthisdisorder.难治性高血压第1页1Contents23DiagnosisEvaluationTreatment难治性高血压第2页Definition

bloodpressureremainsabovegoalthreeanti-hypertensiveagentsofdifferentclassesoneofthe3agentsshouldbeadiureticallagentsshouldbeprescribedatoptimaldoseamounts.Resistanthypertension难治性高血压第3页Prevalence1NHANES53%FraminghamHeartStudy48%ALLHAT250%难治性高血压第4页PatientCharacteristicsPatientCharacteristicsAssociatedWithResistantHypertensionOlderageHighbaselinebloodpressureObesityExcessivedietarysaltingestionChronickidneydiseaseDiabetesLeftventricularhypertrophyBlackraceFemalesexResidenceinsoutheasternUnitedStates难治性高血压第5页PseudoresistancePoorBloodPressureTechniquePoorAdherenceLifestyleFactorsWhite-CoatEffectSecondaryCauses难治性高血压第6页measuringthebloodpressurebeforelettingthepatientsitquietlyuseoftoosmallacuffPoorBloodPressureTechnique难治性高血压第7页amajorcauseoflackofbloodpressurecontrolPoorAdherencelessthan40%ofpatients40%ofpatientsthefirstyearoftreatment45to10yearsoffollow-up3难治性高血压第8页White-CoatEffectStudiesindicatethatasignificantwhite-coateffect(whenclinicbloodpressuresarepersistentlyelevatedwhileout-of-officevaluesarenormalorsignificantlylower)isascommoninpatientswithresistanthypertensionasinthemoregeneralhypertensivepopulation,withaprevalenceintherangeof20%to30%.5难治性高血压第9页LifestyleFactorsObesityisacommonfeatureofpatientswithresistanthypertension.ExcessivedietarysodiumintakeHeavyalcoholintakeisassociatedwithbothanincreasedriskofhypertension,aswellastreatment-resistanthypertension.难治性高血压第10页Non-narcoticanalgesicsNon-steroidalanti-inflammatoryagents,includingaspirin,selectiveCOX-2inhibitorsSympathomimeticagents(decongestants,dietpills,cocaine)Stimulants(methylphenidate,dexmethylphenidate,dextroamphetamine,amphetamine,methamphetamine,modafinil)AlcoholOralcontraceptivesCyclosporineEPONaturallicoriceHerbalcompounds(ephedraormahuang)Drug-RelatedCauses难治性高血压第11页RenalarterystenosisPrimaryaldosteronismRenalparenchymaldiseaseHyperparathyroidismCushing’sdiseasePheochromocytomaSecondaryCausesObstructiveSleepApneaAorticcoarctation难治性高血压第12页EvaluationMedicalHistory:

duration,severity,progressionofthehypertension;treatmentadherence;responsetopriormedicationsAssessmentofAdherenceBloodPressureMeasurementsitquietlycorrectcuffsize;supportthearmatheartleveltheaverageof2readingssupineanduprightbloodpressuresPhysicalExamination难治性高血压第13页Ameanambulatorydaytimebloodpressureof<135/85mmHgisconsideredelevated.EvaluationAmbulatoryBloodPressureMonitoringBiochemicalEvaluationAroutinemetabolicprofileUrinalysisApaired,morningplasmaaldosteronePlasmareninactivityNoninvasiveImaging难治性高血压第14页TreatmentMaximizeAdherence

theuseofalong-actingcombinationofproducts

2.NonpharmacologicalRecommendationsWeightLossDietarySaltRestriction

ModerationofAlcoholIntakeIncreasedPhysicalActivityIngestionofaHigh-Fiber,Low-FatDiet3.TreatmentofSecondaryCausesofHypertension4.PharmacologicalTreatment难治性高血压第15页AliskirenEffectsofaliskirenandvalsartanonplasmaANGIandIIlevels.Aliskirenaloneorincombinationwithvalsartanwastestedin120mildlysodiumdepleted,Nor-motensiveadults(age,18to35years)inadouble-dummy,doubleblind,randomized,placebo-controlled,4-periodcrossoverstudy.Subjectsreceivedsingledosesofaliskiren300mgalone,aliskiren150mgincombinationwithvalsartan80mg,valsartan160mgalone,andplaceboseparatedby2-weekwashoutperiods难治性高血压第16页Thereisnodoubtthataliskirenisaneffectiveantihypertensiveagentandthatateffectivedosesitiswelltolerated.Itappearstobesafe,butthisstatementismadewiththeobviousqualificationforanynoveldrugorclassthatrareorlong-termadverseeventsmaytaketimetobecomeapparent.7AliskirenDOSE:75mg-300mgqdp.o难治性高血压第17页Darusentan

Darusentanprovidesadditionalreductioninbloodpressureinpatientswhohavenotattainedtheirtreatmentgoalswiththreeormoreantihypertensivedrugs.Aswithothervasodilatordrugs,fluidmanagementwitheffectivediuretictherapymightbeneeded.难治性高血压第18页aVaccineAgainstHypertensionTargetingAngiotensinII,ReducesEarly-MorningandDay-TimeBloodPressureCYT006-AngQb

avirus-like-particlebasedconjugatevaccinetargeting(AngII)72mild-to-moderatehypertensivepatients.thevaccinewithanoptimizeddoseregimeninjectionsofeither100or300µg难治性高血压第19页CYT006-AngQbreducedbloodpressureinsituationswheretherenin-angiotensin-aldosteronesystemisstimul