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ResistantHypertension:Diagnosis,Evaluation,andTreatmentJENNY(AScientificStatementFromtheAmericanHeartAssociationProfessionalEducationCommitteeoftheCouncilforHighBloodPressureResearch)Objective

Expandingourunderstandingofthecausesofresistanthypertensionandtherebypotentiallyallowingformoreeffectivepreventionand/ortreatmentwillbeessentialtoimprovethelong-termclinicalmanagementofthisdisorder.1Contents23DiagnosisEvaluationTreatmentDefinition

bloodpressureremainsabovegoalthreeanti-hypertensiveagentsofdifferentclassesoneofthe3agentsshouldbeadiureticallagentsshouldbeprescribedatoptimaldoseamounts.ResistanthypertensionPrevalence1NHANES53%FraminghamHeartStudy48%ALLHAT250%PatientCharacteristicsPatientCharacteristicsAssociatedWithResistantHypertensionOlderageHighbaselinebloodpressureObesityExcessivedietarysaltingestionChronickidneydiseaseDiabetesLeftventricularhypertrophyBlackraceFemalesexResidenceinsoutheasternUnitedStatesPseudoresistancePoorBloodPressureTechniquePoorAdherenceLifestyleFactorsWhite-CoatEffectSecondaryCausesmeasuringthebloodpressurebeforelettingthepatientsitquietlyuseoftoosmallacuffPoorBloodPressureTechniqueamajorcauseoflackofbloodpressurecontrolPoorAdherencelessthan40%ofpatients40%ofpatientsthefirstyearoftreatment45to10yearsoffollow-up3White-CoatEffectStudiesindicatethatasignificantwhite-coateffect(whenclinicbloodpressuresarepersistentlyelevatedwhileout-of-officevaluesarenormalorsignificantlylower)isascommoninpatientswithresistanthypertensionasinthemoregeneralhypertensivepopulation,withaprevalenceintherangeof20%to30%.5LifestyleFactorsObesityisacommonfeatureofpatientswithresistanthypertension.ExcessivedietarysodiumintakeHeavyalcoholintakeisassociatedwithbothanincreasedriskofhypertension,aswellastreatment-resistanthypertension.Non-narcoticanalgesicsNon-steroidalanti-inflammatoryagents,includingaspirin,selectiveCOX-2inhibitors

Sympathomimeticagents(decongestants,dietpills,cocaine)Stimulants(methylphenidate,dexmethylphenidate,

dextroamphetamine,amphetamine,methamphetamine,

modafinil)AlcoholOralcontraceptivesCyclosporineEPONaturallicoriceHerbalcompounds(ephedraormahuang)Drug-RelatedCausesRenalartery

stenosisPrimaryaldosteronismRenalparenchymal

diseaseHyperparathyroidismCushing’sdiseasePheochromocytomaSecondaryCausesObstructiveSleepApneaAorticcoarctationEvaluationMedicalHistory:

duration,severity,progressionofthehypertension;treatmentadherence;responsetopriormedicationsAssessmentofAdherenceBloodPressureMeasurementsitquietlycorrectcuffsize;supportthearmatheartleveltheaverageof2readingssupineanduprightbloodpressuresPhysicalExaminationAmeanambulatorydaytimebloodpressureof<135/85mmHgisconsideredelevated.EvaluationAmbulatoryBloodPressureMonitoringBiochemicalEvaluationAroutinemetabolicprofileUrinalysisApaired,morningplasmaaldosterone

PlasmareninactivityNoninvasiveImagingTreatmentMaximizeAdherence

theuseofalong-actingcombinationofproducts

2.NonpharmacologicalRecommendationsWeightLossDietarySaltRestriction

ModerationofAlcoholIntakeIncreasedPhysicalActivityIngestionofaHigh-Fiber,Low-FatDiet3.TreatmentofSecondaryCausesofHypertension4.PharmacologicalTreatmentAliskirenEffectsofaliskirenandvalsartanonplasmaANGIandIIlevels.Aliskirenaloneorincombinationwithvalsartanwastestedin120mildlysodiumdepleted,Nor-motensiveadults(age,18to35years)inadouble-dummy,doubleblind,randomized,placebo-controlled,4-periodcrossoverstudy.Subjectsreceivedsingledosesofaliskiren300mgalone,aliskiren150mgincombinationwithvalsartan80mg,valsartan160mgalone,andplaceboseparatedby2-weekwashoutperiods

Thereisnodoubtthataliskirenisaneffectiveantihypertensiveagentandthatateffectivedosesitiswelltolerated.Itappearstobesafe,butthisstatementismadewiththeobviousqualificationforanynoveldrugorclassthatrareorlong-termadverseeventsmaytaketimetobecomeapparent.7AliskirenDOSE:75mg-300mgqd

p.oDarusentan

Darusentanprovidesadditionalreductioninbloodpressureinpatientswhohavenotattainedtheirtreatmentgoalswiththreeormoreantihypertensivedrugs.Aswithothervasodilatordrugs,fluidmanagementwitheffectivediuretictherapymightbeneeded.aVaccineAgainstHypertensionTargetingAngiotensinII,ReducesEarly-MorningandDay-TimeBloodPressureCYT006-AngQb

avirus-like-particlebasedconjugatevaccinetargeting(AngII)72mild-to-moderatehypertensivepatients.thevaccinewithanoptimizeddoseregimeninjectionsofeither100or300μg

CYT006-AngQbreducedbloodpressureinsituationswheretherenin-angiotensin-aldosteronesystem

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