内科学教学课件：23 Hypertension-prevention and treatment

Hypertension

clinicalmanagementupdate思考题Antihypertensivemanagementmeanspharmaceuticaltherapies?抗高血压治疗就是药物治疗？ThebenefitsofantihypertensivedrugsdependonthereductionofBP?

降压幅度是抗高血压治疗临床获益的主要来源？Sources:WHOWorldHealthReport2000,CVDinfobase

18,000,000fromhigh-incomecountries

42,000,000fromlow-incomecountriesImportanceofHypertensionandCVD60,000,000HTNpatientshavetherisktodeveloptoMI,stroke,andheartfailureWorldHeartFederationEpidemiologyofHypertensionHypertensionEpidemiologySinglelargestcontributortodeathworldwideEvery20/10mmHgincreaseinBPcorrelateswithadoublingof10-yearcardiovascularmortalityDramaticallyincreasesriskofstroke,heartattack,heartfailure,&kidneyfailureOnlyhalfofalltreatedhypertensivesarecontrolledtoestablishedBPtargetsHighprevalence:Affects1in3adults1Bpeopleworldwide

1.6Bby202535%

Treated&

Controlled30%

Untreated35%

TreatedbutUncontrolledChobanianetal.Hypertension.

2003;42(6):1206–1252.4PrevelenceofHTNinUSAJNC-VI.ArchInternMed.1997;157:2413-2446.NHANESIIIBP

140/90mmHgorontherapiesPercenthypertensive18-2930-3940-4950-5960-6970-7980+Age3%9%18%38%51%66%72%020406080PrevelenceofHTNinChinaGuDF,etal.Hypertension.2002;40:920-927010203040506030354045505560657075男性女性1991Nationalsurvey:prevelence=11.26%2000－2001InterASIA

study：prevelenceinage35-74=27.2%，about13,000,000patientsPrevelence%age2000－2001InterASIAstudyGuDF,etal.Hypertension.2002;40:920-927PrevelenceofHTNinChina中国高血压的现状：各年龄组的患病率都在增加(%)PrevalenceRateReportonCardiovascularDiseaseinChina(2008-2009)■1979■1991

200294%97%105%170%184%173%143%130%114%93%77%60%47%2010年中国成年人（18岁以上）高血压患病情况。收缩压为(130.8±21.3)mmHg舒张压为(80.4±11.7)mmHg中国成年人高血压患病率为33.5％，(95％CI：31.6％-35.4％)。

男性：35.1%，95％CI：33.1％-37.1％，女性：31.8％，95％CI：29.8％～33.9％3.3亿成年人高血压患者BPControlRatesTrendsinawareness,treatment,andcontrolofhigh

bloodpressureinadultsages18–74NationalHealthandNutritionExaminationSurvey,PercentII1976–80II(Phase1)1988–91II(Phase2)1991–941999–2000Awareness51736870Treatment31555459Control10292734Sources:Unpublisheddatafor1999–2000computedbyM.Wolz,NationalHeart,Lung,andBloodInstitute;JNC6.中国高血压治疗现状知晓率治疗率控制率200230.2%24.7%6.1%199126.6%12.2%2.9%2004年发布的《中国居民营养与健康现状》调查结果显示：ChinJhypervol12No.6487-489我国高血压流行病学现状26.612.22.930.224.76.10102030405060708090100知晓率治疗率控制率19912002百分比

(%)!中国居民营养与健康现状调查--中华人民共和国卫生部、中华人民共和国科学技术部、中华人民共和国国家统计局2004年10月12日LSLiu,etal.AmJHypertens2014,April3online42.69.334.120142012年我国高血压

患病率，知晓率，治疗率和控制率国家卫计委疾病预防控制局，中国居民营养与慢性病状况报告(2015年)，人民卫生出版社25.2%2012年中国18岁及以上居民高血压患病率为25.2%2014最新调查数据：

中国35-74岁人群的高血压患病率达32.5%JAMAInternMed.doi:10.1001/jamainternmed.2016.0190PublishedonlineMarch14,2016Age-andSex-SpecificAssociationofHypertensionWithMortalityDuetoCVDJAMAInternMed.doi:10.1001/jamainternmed.2016.0190PublishedonlineMarch14,2016ChinJhypervol12No.6487-489患病率患病人数高血压18.8%>1.6亿糖尿病2.6%>2000万糖耐量异常1.90%2000万超重22.80%2亿肥胖7.10%>6000万高TC(>5.72mmol/L)2.90%1.6亿人次高TG(>1.7mmol/L)11.90%低HDL(<0.91mmol/L)7.40%中国高血压治疗现状Riskofhypertension(%)Residuallifetimeriskofdevelopinghypertensionamongpeoplewithbloodpressure<140/90mmHgYearsLifetimeRiskofDevelopingHypertensionBeginningatAge55MenWomenVasanRS,etal.JAMA.2002;287:1003-1010.CVMortalityRiskDoubleswith

Each20/10mmHgBPIncrement**Individualsaged40-69years,startingatBP115/75mmHg.CV,cardiovascular;SBP,systolicbloodpressure;DBP,diastolicbloodpressureLewingtonS,etal.Lancet.2002;60:1903-1913.TheJNC7Report.JAMA.2003;289:2560-2572.CV

mortality

riskSBP/DBP(mmHg)012345678115/75135/85155/95175/105MortalityAccordingtoBloodPressure

inMenAge50to69SocietyofActuaries.BloodPressureStudy,1993.Ratio(%)ofactualtoexpectedmortalitySystolicbloodpressure(mmHg)Diastolicbloodpressure(mmHg)SBP(mmHg)DBP(mmHg)SBP,DBPandCADevents(MRFIT)TherelativeriskofstrokeandCADinHTN4.002.001.000.500.254.002.001.000.500.257prospectivestudies，843eventsStrokeBaselineDBP通常DBP123 4576 84 91 98105mmHg9prosprectivestudies，4856eventsCAD通常DBP123 4576 84 91 98105mmHgCumulativeincidenceofCHFandHTNstatusmen，age60–69women，age60–69Stage2Stage1normotension(year)(year)Cumulativeincidence(%)Levy(1996)0051015202505101520250246810121416246810121416Stage2Stage1normotension临床实践Age，bloodpressureandstrokeAge,bloodpressureandCADProspectiveStudiesCollaboration。Age-specificrelevanceofusualbloodpressuretovascularmortality:ameta-analysisofindividualdataforonemillionadultsin61prospectivestudies。Lancet2002;360:1903–1324亚洲澳洲人数500,81998,790%女性33.745.7年龄(岁)-平均45.053.2-标准差9.514.4-范围20-10720-104APCSC人口统计状况25StudiescurrentlyinAPCSC26SBPandFatalorNon-FatalStroke(Ischemic)Pforheterogeneity=0.001澳洲亚洲+10mmHg:1.24(1.15-1.35)+10mmHg:1.53(1.48-1.59)

HazardratioMeanusualSBP(mmHgl)

110120130140150160170

1101201301401501601700.51.02.04.08.00.51.02.04.08.027Pforheterogeneity=0.0002澳洲亚洲Hazardratio+10mmHg:1.20(1.04-1.35)+10mmHg:1.70(1.64-1.76)MeanusualSBP(mmHgl)SBPandFatalorNon-fatalStroke(Hemorreagic)28Pforheterogeneity=0.002澳洲亚洲Hazardratio+10mmHg:1.22(1.18-1.26)+10mmHg:1.31(1.26-1.35)MeanusualSBP(mmHgl)SBPandFatalCoronaryDiseasePathologyandPathophisiologyRiskFactorsforHypertensionDyslipidemiaRace

GeneticDiabetesLackofexerciseAlcohol

Stress(?)obeseACEReninAngiotensinogenAngiotensinI(10aa)AngiotensinII(8aa)StimulusAngiotensinReceptorLowsaltintakeLowbloodvolumeLowbloodpressureSodiumretentionVasoconstrictionTheRenin-AngiotensinSystemPathwayIncidence(%)PlasmaReninActivityBrunnerHRetal.NEnglJMed.1972;286:441-449.IncidenceofCVComplicationsAsaFunctionofPlasmaReninActivityinHypertensionClassificationofBloodPressureforAdults2010年中国高血压防治指南一、血压的定义与分类血压水平的定义和分类（mmHg）

类别收缩压（mmHg）舒张压（mmHg）正常血压正常高值高血压１级高血压（“轻度”）２级高血压（“中度”）３级高血压（“重度”）单纯收缩期高血压＜１２０１２０～１３９≧１４０１４０～１５９１６０～１７９≧１８０≧１４０＜８０８０～８９≧９０９０～９９１００～１０９≧１１０＜９０ChinJhypervol12No.6483-486BloodPressureMeasurementPatientsshouldbeseatedwithbacksupportedandarmbaredandsupported.Patientsshouldrefrainfromsmokingoringestingcaffeinefor30minutespriortomeasurement.Measurementshouldbeginafteratleast5minutesofrest.Appropriatecuffsizeandcalibratedequipmentshouldbeused.BothSBPandDBPshouldberecorded.Twoormorereadingsshouldbeaveraged.AdvantagesofSelf-MeasurementIdentifies“white-coathypertension”AssessesresponsetomedicationImprovesadherencetotreatmentPotentiallyreducescostsUsuallyprovideslowerreadingsthanthoserecordedinclinic(hypertensionisdefinedasSBP>135orDBP>85mmHg)AmbulatoryMeasurementAmbulatorymonitoringcanprovide:readingsthroughoutdayduringusualactivitiesreadingsduringsleeptoassessnocturnalchangesmeasuresofSBPandDBPloadAmbulatoryreadingsareusuallylowerthaninclinic(hypertensionisdefinedasSBP>135orDBP>85mmHg)RecommendationsforFollowupBasedonInitialMeasurementsEvaluationObjectivesToidentifyknowncausesToassesspresenceorabsenceoftargetorgandamageandcardiovasculardiseaseToidentifyotherriskfactorsordisordersthatmayguidetreatmentEvaluationComponentsMedicalhistoryPhysicalexaminationRoutinelaboratorytestsOptionaltestsMedicalHistoryDurationandclassificationofhypertensionPatienthistoryofcardiovasculardiseaseFamilyhistorySymptomssuggestingcausesofhypertensionLifestylefactorsCurrentandpreviousmedicationsPhysicalExaminationBloodpressurereadings(2ormore)VerificationincontralateralarmHeight,weight,andwaistcircumferenceFunduscopicexaminationExaminationoftheneck,heart,lungs,abdomen,andextremitiesNeurologicalassessmentLaboratoryTestsandOtherDiagnosticProceduresDeterminepresenceoftargetorgandamageandotherriskfactorsSeekspecificcausesofhypertensionLaboratoryTestsRecommendedBeforeInitiatingTherapyUrinalysisCompletebloodcountBloodchemistry(potassium,sodium,creatinine,andfastingglucose)Lipidprofile(totalcholesterolandHDLcholesterol)12-leadelectrocardiogramOptionalTestsandProceduresCreatinineclearanceMicroalbuminuria24-hoururinaryproteinSerumcalciumSerumuricacidFastingtriglyceridesLDLcholesterolGlycosolatedhemoglobinThyroid-stimulatinghormonePlasmareninactivity/urinarysodiumdeterminationLimitedechocardiographyUltrasonographyMeasurementofankle/armindexExamplesofIdentifiable

CausesofHypertensionRenovasculardiseaseRenalparenchymaldiseasePolycystickidneysAorticcoarctationPheochromocytomaPrimaryaldosteronismCushingsyndromeHyperparathyroidismExogenouscausesComponentsofCardiovascularRiskinPatientsWithHypertensionMajorRiskFactors:

SmokingDyslipidemiaDiabetesmellitusAgeolderthan60yearsSex(menorpostmenopausalwomen)FamilyhistoryofcardiovasculardiseaseCVDRiskHTNprevalence~50millionpeopleintheUnitedStates.TheBPrelationshiptoriskofCVDiscontinuous,consistent,andindependentofotherriskfactors.Eachincrementof20/10mmHgdoublestheriskofCVDacrosstheentireBPrangestartingfrom115/75mmHg.PrehypertensionsignalstheneedforincreasededucationtoreduceBPinordertopreventhypertension.ClinicalRiskFactorsfor

StratificationofPatientsWithHypertensionHeartdiseasesStrokeortransientischemicattackNephropathyPeripheralarterialdiseaseRetinopathyRiskStratificationRiskStratificationTreatmentStrategiesand

RiskStratificationPrimaryPreventionPrimarypreventionoffersanopportunitytointerruptthecostlycycleofmanaginghypertension.Apopulation-wideapproachcanreducemorbidity

andmortality.Mostpatientswithhypertensiondonotsufficientlychangetheirlifestyleoradheretodrugtherapyenoughtoachievecontrol.Bloodpressurerisewithageisnotinevitable.Lifestylemodificationshavebeenshowntolowerbloodpressure.GoalofHypertension

PreventionandManagementToreducemorbidityandmortalitybytheleastintrusivemeanspossible.Thismaybeaccomplishedbyachievingandmaintaining:SBP<140mmHgDBP<90mmHgcontrollingothercardiovascularriskfactors

CHDIncidenceRate/

1000PersonYearsHistoricalLessonsAboutHypertensionCumulativeFatal&NonfatalEndpointsTHEFRAMINGHAMSTUDYTHEVET.ADM.STUDYIIAnnInternMed.1961;55:33-50JAMA.1970;213:1143-1152HypertensionIncreases

MorbidityandMortalityTreatmentDecreasesMorbidityandMortality

GoalsofTherapyforHTN

ReduceCVDandrenalmorbidityandmortality.TreattoBP<140/90mmHgorBP<130/80mmHginpatientswithdiabetesorchronickidneydisease.AchieveSBPgoalespeciallyinpersons>50yearsofage.BenefitsofLoweringBP

AveragePercentReduction Strokeincidence 35–40%

Myocardialinfarction 20–25% Heartfailure 50%单纯收缩压升高(%)0−10−20−30−40−500−10−20−30−40−50(%)脑卒中冠心病总死亡心血管死亡非心血管死亡致死和致残事件死亡率收缩压和舒张压均升高脑卒中冠心病总死亡心血管死亡非心血管死亡致死和致残事件死亡率降压治疗的临床获益ESH-ESCHypertensionGuidelines.JHypertens.2003.<0.01<0.01<0.001NS<0.001<0.0010.020.01NS<0.001血压控制目标值高血压患者

<140/90mmHg糖尿病患者

<130/80mmHg肾功受损：蛋白尿<1g/日 <130/80mmHg肾功受损：蛋白尿>1g/日

<125/75mmHg老年人：SBP<150mmHg2004年中国高血压防治指南LifestyleModificationsForPreventionandManagementLoseweightifoverweight.Limitalcoholintake.Increaseaerobicphysicalactivity.Reducesodiumintake.Maintainadequateintakeofpotassium.ForOverallandCardiovascularHealthMaintainadequateintakeofcalciumandmagnesium.Stopsmoking.Reducedietarysaturatedfatandcholesterol.LifestyleModificationModificationApproximateSBPreduction

(range)Weightreduction5–20

mmHg/10kgweightlossAdoptDASHeatingplan8–14mmHgDietarysodiumreduction2–8mmHgPhysicalactivity4–9mmHgModerationofalcoholconsumption2–4mmHgPharmacologicTreatmentDecreasescardiovascularmorbidityandmortalitybasedonrandomizedcontrolledtrials.Protectsagainststroke,coronaryevents,heartfailure,progressionofrenaldisease,progressiontomoreseverehypertension,andall-causemortality.SpecialConsiderations

inSelectingDrugTherapyDemographicsCoexistingdiseasesandtherapiesQualityoflifePhysiologicalandbiochemicalmeasurementsDruginteractionsEconomicconsiderationsDrugTherapyAlowdoseofinitialdrugshouldbeused,slowlytitratingupward.Optimalformulationshouldprovide24-hourefficacywithonce-dailydosewithatleast50%ofpeakeffectremainingatendof24hours.Combinationtherapiesmayprovideadditionalefficacywithfeweradverseeffects.Classesof

AntihypertensiveDrugsACEinhibitorsAdrenergicinhibitorsAngiotensinIIreceptorblockersCalciumantagonistsDirectvasodilatorsDiureticsInitialDrugChoicesAlgorithmforTreatmentofHypertension(continued)NotatGoalBloodPressure(<140/90mmHg)

lowergoalsforpatientswithdiabetesorrenaldiseaseBeginorContinueLifestyleModificationsNotatGoalBloodPressureInitialDrugChoicesUncomplicatedCompellingIndicationsNotatGoalBloodPressureAlgorithmforTreatmentof

Hypertension

(continued)

Startatlowdoseandtitrateupward.Low-dosecombinationsmaybeappropriate.SpecificIndicationsInitialDrugChoices*UncomplicatedDiuretics

-blockersAlgorithmforTreatmentof

Hypertension(continued)*Basedonrandomizedcontrolledtrials.InitialDrugChoices*AlgorithmforTreatmentof

Hypertension

(continued)CompellingIndications

HeartfailureACEinhibitorsDiureticsMyocardialinfarction

-blockers(non-ISA)ACEinhibitors(withsystolicdysfunction)Diabetesmellitus(type1)withproteinuriaACEinhibitorsIsolatedsystolichypertension(olderpersons)DiureticspreferredLong-actingdihydropyridinecalciumantagonists*Basedonrandomizedcontrolledtrials.InitialDrugChoicesSpecificindicationsforthefollowingdrugs:AlgorithmforTreatmentof

Hypertension

(continued)

ACEinhibitorsAngiotensinIIreceptorblockers

-blockers

-

-blockers

-blockersCalciumantagonistsDiureticsSpecificDrugIndicationsAngina

-blockersCalciumantagonistsAtrialtachycardiaandfibrillation

-blockersNondihydropyridine calciumantagonistsSomeantihypertensivedrugsmayhavefavorableeffectsoncomorbidconditions:HeartfailureCarvedilolLosartanMyocardialinfarctionDiltiazemVerapamilSpecificIndications(continued)Cyclosporine-inducedhypertensionCalciumantagonistsDiabetesmellitus(1and2)withproteinuriaACEinhibitors(preferred)CalciumantagonistsDiabetesmellitus(type2)Low-dosediureticsDyslipidemia

-blockersProstatism(benignprostatichyperplasia)

-blockersRenalinsufficiency(cautioninrenovascularhypertensionandcreatinine

3mg/dL [

265.2

mol/L])ACEinhibitorsSomeantihypertensivedrugsmayhavefavorableeffectsoncomorbidconditions:SpecificIndications

(continued)EssentialtremorNoncardioselective

-blockersHyperthyroidism

-blockersMigraine

Noncardioselective

-blockersNondihydropyridinecalcium antagonistsOsteoporosis

ThiazidesPerioperativehypertension

-blockersSomeantihypertensivedrugsmayhavefavorableeffectsoncomorbidconditions:NotatGoalBloodPressure(<140/90mmHg)NoresponseortroublesomesideeffectsInadequateresponsebutwelltoleratedSubstituteanotherdrugfromdifferentclassAddsecondagentfromdifferentclass(diureticifnotalreadyused)NotatGoalBloodPressure(<140/90mmHg)InitialDrugChoicesAlgorithmforTreatmentof

Hypertension

(continued)NotatGoalBloodPressure(<140/90mmHg)Continueaddingagentsfromotherclasses.Considerreferraltoahypertensionspecialist.SubstitutedrugfromdifferentclassAddsecondagentfromdifferentclassAlgorithmforTreatmentofHypertension(continued)血压)维持血压的主要机制DirectAdrenergicSaltHormones体液/激素机制(血管紧张素II、去甲肾上腺素、内皮素)直接机制(自动调节)肾上腺素能机制(，)盐机制(氯化钠)CombinationTherapies

-adrenergicblockersanddiureticsACEinhibitorsanddiureticsAngiotensinIIreceptorantagonistsanddiureticsCalciumantagonistsandACEinhibitorsOthercombinationsCombinationTherapiesAHA《心脏疾病和卒中年统计数据》2013版报告：

美国心血管死亡近10年下降32.7%Circulation.2013;

127:

e6-e245心血管死亡脑卒中死亡在1999-2009年间，美国心血管死亡卒中导致的死亡大幅降低美国血压控制率的最新数据——

NHANES2001-2010调查结果公布Circulation.2012;126:2105-2114.美国国家健康与营养调查NHANES2001-2010调查研究9320例年龄大于18岁的高血压患者高血压患者的血压控制率从研究初始（2001-2002年）的28.7%大幅上升至结束时（2009-2010年）的47.2%！NHANESstudypopulation:9,320hypertensiveadults(≥18yrs)randomlyselectedfromU.S.populationSurveyedannually,reportedevery2yearsInterviews,physicalexaminationsandprescriptiondruguserecordedTrendsinAnti-HTNMedicationuseandBPControlamongU.S.AdultswithHTNGuG,etal.Circulation.126:2105-2114,2012.DrugClassesandTherapy2001–2002%2009–2010%PtrendDiuretics30.035.80.01    Monotherapy2.73.30.46    Polytherapy27.332.50.02

Thiazidediuretics22.427.60.02    Monotherapy1.6*2.50.09    Polytherapy20.825.10.04β-blockers20.331.9<0.01    Monotherapy4.65.90.28    Polytherapy15.725.9<0.01

CCBs19.220.90.65    Monotherapy5.53.70.05    Polytherapy13.717.20.14

ACEIs25.533.3<0.01    Monotherapy9.711.20.33    Polytherapy15.822.2<0.01

ARBs10.522.2<0.01    Monotherapy3.04.9<0.01    Polytherapy7.616.1<0.01*Estimateisunstable:therelativestandarderroris>30%.Antihypertensivemedicationuseincreased

63.5%→77.3%(Ptrend<0.01)Useofmultipleagentsincreased

36.8%→47.7%(Ptrend<0.01)Hypertensioncontrolratesincreased

Overall28.7%→47.2%(Ptrend<0.01)

Ontreatment44.6%→60.3%(Ptrend<0.01)

Single-pillcombination44.2%→68.8%(Ptrend<0.001)

Multiple-pillcombination44.9%→59.3%(Ptrend<0.001)BPgoalachievement <130/80 <140/90

Nocomorbidities --- 69.5% WithCKD 43.7% 61.7% WithDiabetes 44.6% 67.0%TRENDSINANTI-HTNMEDICATIONUSEANDBPCONTROL2001-2010GuG,etal.Circulation.126:2105-2114,2012.Antihypertensivemedicationuseincreased

63.5%→77.3%(Ptrend<0.01)Useofmultipleagentsincreased

36.8%→47.7%(Ptrend<0.01)Hypertensioncontrolratesincreased

Overall28.7%→47.2%(Ptrend<0.01)

Ontreatment44.6%→60.3%(Ptrend<0.01)

Single-pillcombination44.2%→68.8%(Ptrend<0.001)

Multiple-pillcombination44.9%→59.3%(Ptrend<0.001)BPgoalachievement <130/80 <140/90

Nocomorbidities --- 69.5% WithCKD 43.7% 61.7% WithDiabetes 44.6% 67.0%TRENDSINANTI-HTNMEDICATIONUSEANDBPCONTROL2001-2010GuG,etal.Circulation.126:2105-2114,2012.78.3%的服药者血压控制达标Diuretics(particularlythiazides)arethemostcommonlyuseddrugclass,primarilyincombinations.ACEIsarethesecondmostcommonlyuseddrugclass.ACEIandARBusehasincreasedsignificantlyoverthelastdecade,bothoverallandincombinations.β-blockerusehasincreasedby65%overthelastdecade,primarilyincombinations.CCBusehasremainedconstantoverthelastdecade.SUMMARYGuG,etal.Circulation.126:2105-2114,2012.ToachieveBPgoals，Patientsoncombinationtherapyweremorelikelythanthoseonmonotherapy.+55%forsingle-pillcombinations;+26%formultiple-pillcombinations)SUMMARY(Continued)GuG,etal.Circulation.126:2105-2114,2012.血压水平与心血管死亡的绝对危险Age-adjustedannual

incidenceofCVdeathper10001642-50%-75%基线控制率37.237.9ACCOMPLISH:降压达标率ACEI/HCTZN=5733控制率(%)ACEI/CCBN=571310203040506070809078.581.7P<0.001（30个月随访时）

控制定义为血压<140/90mmHgACCOMPLISH：主要心血管终点累积事件率HR(95%CI):0.80(0.72,0.90)20%第一个CV事件/死亡出现的时间(天)p=0.0002ACEI/HCTZACEI/CCB6505262008年3月初步结果临床实践中，起始联合治疗比例逐年升高JamesB.Byrd,etal.AmHeartJ.Aug1,2011;162(2):340–346.一项回顾性研究，数据源自美国国家心脏、肺和血液研究所(NHLBI)赞助的心血管研究网络，共纳入2002-2007年间的161,585例新诊断为高血压，且起始接受治疗的患者，评估起始联合治疗的比例接受起始联合治疗的患者比例(%)年份1期高血压2期高血压我国高血压流行病学现状26.612.22.930.224.76.10102030405060708090100知晓率治疗率控制率19912002百分比

(%)!中国居民营养与健康现状调查--中华人民共和国卫生部、中华人民共和国科学技术部、中华人民共和国国家统计局2004年10月12日LSLiu,etal.AmJHypertens2014,April3online42.69.334.1201427.3%的服药者血压控制达标RenalSympatheticActivation:EfferentNerves

KidneyasRecipientofSympatheticSignalsRenalEfferentNerves↑ReninReleaseRAASactivation↑SodiumRetention↓RenalBloodFlow110HypertrophyArrhythmiaOxygenConsumptionVasoconstrictionAtherosclerosisInsulinResistanceRenalSympatheticActivation:AfferentNerves

KidneyasOriginofCentralSympatheticDriveRenalAfferentNerves

↑ReninReleaseRAASactivation↑SodiumRetention↓RenalBloodFlowSleepDisturbances111NervesarisefromT10-L2ThenervesarborizearoundthearteryandprimarilyliewithintheadventitiaRenalNerveAnatomy

VesselLumenMediaAdventitiaRenalNerves112112RenalNerveAnatomyAllowsa

Catheter-BasedApproach113Renalarteryaccessviastandardinterventionaltechnique4-6two-minutetreatmentsperarteryProprietaryRFgeneratorAutomatedLowpowerBuilt-insafetyalgorithmsSpacingofe.g.5mm.SymplicityHTN-2TrialInclusionCriteria:OfficeSBP≥160mmHg(≥150mmHgwithtypeIIdiabetesmellitus)Stabledrugregimenof3+moreanti-HTNmedicationsAge18-85yearsExclusionCriteria:HemodynamicallyoranatomicallysignificantrenalarteryabnormalitiesorpriorrenalarteryinterventioneGFR<45mL/min/1.73m2(MDRDformula)Type1diabetesmellitusContraindicationtoMRIStenoticvalvularheartdiseaseforwhichreductionofBPwouldbehazardousMI,unstableangina,orCVAintheprior6monthsSymplicityHTN-2Investigators.Lancet.2010;376:1903-1909.Treatment-resistant

HTNpopulationBLOBP178/97mmHg49RDN,51ControlAge58yearsBMI31kg/m²40%withDiabeteseGFR77*Avg#meds5.2RDNandControlgroups

generallywell-matched*MDRD,ml/min/1.73m2AssessedforEligibility(n=190)ExcludedDuringScreening,PriortoRandomisation(n=84)BP<160atBaselineVisit(after2-weeksofmedicationcomplianceconfirmation)(n=36;19%)Ineligibleanatomy(n=30;16%)Declinedparticipation(n=10;5%)Otherexclusioncriteriadiscoveredafterconsent(n=8;4%)Randomised(n=106)AllocatedtoRDNn=52Treatedn=49Analysable6-monthPrimaryEnd-PointScreeningAllocatedtoControln=54Controln=51Analysable12-monthPost-Randomisation12-monthpost-RDNn=47Perprotocol,6-moPost-RDN(Crossover)n=35Not-per-protocol*,6-moPost-RDN(Crossover)n=9*Crossed-overwithineligibleBP(<160mmHg)SymplicityHTN-2:PatientdispositionCrossovern=462LTFURDNandControlPopulationsWell-matched,SevereTreatmentResistantHypertensives

RDN(n=52)Control

(n=54)p-ValueBaselinesystolicBP(mmHg)178±18178±160.97BaselinediastolicBP(mmHg)97±1698±170.80Numberanti-HTNmedications5.2±1.55.3±1.80.75Age58±1258±120.97Gender(female)(%)35%50%0.12Race(Caucasian)(%)98%96%>0.99BMI(kg/m2)31±531±50.77Type2diabetes40%28%0.22Coronaryarterydisease19%7%0.09Hypercholesterolemia52%52%>0.99eGFR(MDRD,ml/min/1.73m2)77±1986±200.013Serumcreatinine(mg/dL)1.0±0.30.9±0.20.003Urinealb/creatratio(mg/g)*128±363109±2540.64CystatinC(mg/L)†0.9±0.20.8±0.20.16Heartrate(bpm)75±1571±150.23*n=42forRDNandn=43forControl.Wilcoxonrank-sumtestfortwoindependentsamplesusedforbetween-groupcomparisonsofUACR.†n=39forRDNandn=42forControl.

ExpandedresultspresentedattheAmericanCollegeofCardiologyAnnualMeeting2012(Esler,M.)SymplicityHTN-2:PrimaryEndpointandLatestFollow-up∆fromBaselineto6Months(mmHg)PrimaryEndpoint:84%ofRDNpatientshad≥10mmHgreductioninSBP10%ofRDNpatientshadnoreductioninSBPSystolicDiastolicSystolicDiastolicExpandedresultspresentedattheAmericanCollegeofCardiologyAnnualMeeting2012(Esler,M.)RDN(n=47)∆fromBaselineto12Months(mmHg)SystolicDiastolicPrimaryEndpoint(6MpostRandomisation)LatestFollow-up(12MpostRandomisation)LatestFollow-up:Controlcrossover(n=35):-24/-8mmHg(AnalysisonpatientswithSBP≥160mmHgat6M)p<0.01for

frombaselinep<0.01fordifferencebetweenRDNandControlSymplicityHTN-2:MedicationChangesat6and12MonthsPost-RenalDenervationRDN(n=47)6month12monthsDecrease(#MedsorDose)20.9%(9/43)27.9%(12/43)Increase(#MedsorDose)11.6%(5/43)18.6%(8/43)Crossover(n=35)6monthspost-RDNDecrease(#MedsorDose)18.2%(6/33)Increase(#MedsorDose)15.2%(5/33)PhysicianswereallowedtomakechangestomedicationsOncethe6monthprimaryendpointwasreached**FurtheranalysisofMedicationsisongoing抗高血压药物改善心血管预后共识：血压从115/75mmHg起，每升高20/10mmHg，心血管终点事件发生率翻倍降压治疗的主要目的：降低因心血管原因致死和致残降压治疗的临床获益主要（90%）来自于血压降低降压治疗的目标血压水平：<140/90mmHg>70%的高血压患者须联合降压药物治疗降压达标的同时控制其它危险因素未明：越低越好？<120/80mmHg越早越好？一级预防：高危？中高危？中危？EffectsofBPReductiononCVDeventsLancet2014;384:591–98血压水平与心血管死亡的绝对危险Age-adjustedannual

incidenceofCVdeathper10001642-50%-75%2015-11-0963rdAHACongress

Orlando，FLDemographicandBaselineCharacteristicsBPChangesinthe2Groups

overtheCourseoftheTrialSPRINT:强化降压