高血压的择时治疗

高血压的择时给药内容提纲:简介文献分析与评论

结论

123一、简介血压昼夜节律

血压是血管内流动的血液对于单位面积血管壁的侧压力，在生理状态下，机体血压呈昼夜节律性波动。健康机体血压全天呈现双峰一谷、昼高夜低的杓型曲线：张振服,刘启德,杨蕾.血压昼夜节律特征及其分子调控机制[J].现代生物医学进展,2011,11(6):1181-1183.一、简介

但高血压患者、老年人、甚至部分健康人群中，其血压的昼夜节律特征可能有所变化。习惯上，根据夜间血压的下降情况分可将其分为4型：（1）杓型(dippers)：夜间血压较日间下降10～20%；（2）非杓型(non-dippers)：夜间血压下降0～10%；（3）超杓型或深杓型(over-dippers或extreme-dippers)：夜间下降>20%；（4）反杓型(reverse-dippers)：夜间血压水平高于日间者。

大量临床资料研究表明，血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系，是独立于血压水平的重要致病因素。目前高血压治疗重心：保护靶器官和降低心、脑血管疾病的发生率和死亡率。充分控制血压，包括增加药物剂量、改进降压药物以及联合运用具有协同作用的药物等措施。无论是单一药物治疗,还是联合药物治疗,都存在一个共同点,即把降压药在早上一次性服用(白天活动的开始或是在早饭时)。高血压患者中存在较高的非杓形血压发病率大多数降压药不能持续平稳作用24h针对所有高血压患者都使用早上一次性给药的治疗策略是否恰当？问题一、简介

近年来，国内外许多学者提出，全面的高血压治疗策略是在控制血压的同时恢复高血压患者血压正常的近日节律，这就需要调整降压药的给药时间。蒲小波,杜一平.血压的近日节律与高血压的时间治疗学[J].重庆医学,2009,38(21):2748-50.一、简介二、文献分析与评论Twoearlierconductedmorbiditytrials—theSyst-EurandtheHeartOutcomesPreventionEvaluation(HOPE)studies.IntheSyst-Eurtrial,participantswererandomizedtoaneveningscheduleofeitherplaceboorthedihydropyridinecalciumchannelblockernitrendipine.

IntheHOPEstudy,participantsintheactive-treatmentgroupingestedtheangiotensin-convertingenzymeinhibitorramiprilatbedtime,acriticalpieceofinformationwithheldfromtheoriginalpublication.1、StaessenJA,ThijsL,FagardR,andetal.TheSystolicHypertensioninEuropeTrialInvestigators.Predictingcardiovascularriskusingconventionalvsambulatorybloodpressureinolderpatientswithsystolichypertension[J].JAMA,1999,282:539–546.2、YusufS,SleightP,PogueJ,andetal.TheHeartOutcomesPreventionEvaluationStudyInvestigators.Effectsofanangiotensin-converting-enzymeinhibitor,ramipril,oncardiovasculareventsinhigh-riskpatients[J].N.Engl.J.Med,2000,342:145–153.二、文献分析与评论SmolenskyMH,HermidaRC,AyalaDE,andetal.Administration-time-dependenteffectsofbloodpressure-loweringmedications:basisforthechronotherapyofhypertension[J].BloodPressMonit.,2010,15:173–180.THEMAPECSTUDY:HYPERTENSIONCHRONOTHERAPYANDCVDRISKAtotalof2156hypertensivesubjectswereevaluatedby48-hABPMatbase-lineandwithidenticalassessmentconductedannually,ormorefrequently(quarterly)ifadjustmentoftreatmentwasrequired.Atbaseline,thetwotreatment-timegroupsweremostlycomparableintermsoftheirclinicandmeanambulatorySBPandDBPandprevalenceofnon-dippingBPpattern.FrancescoPortaluppi,MichaelH.Smolensky.PERSPECTIVESONTHECHRONOTHERAPYOFHYPERTENSIONBASEDONTHERESULTSOFTHEMAPECSTUDY[J].ChronobiologyInternational,2010,27(8):1652–1667.MonitorizaciónAmbulatoriaparaPrediccióndeEventosCardiovasculares,i.e.,AmbulatoryBloodPressureMonitoringforPredictionofCardiovascularEvent(MAPEC).Results:Subjectswhoingested≥1oftheirmedicationsatbedtimeshowedattheirlastavailableevaluationsignificantlylowermeansleeptimeBP,highersleep-timerelativeBPdecline(anindexofBPdippingcalculatedas[(awakeBPmean−asleepBPmean)/awakeBPmean]×100),reducedprevalenceofnon-dipping(34%versus62%;p<.001),andhigherprevalenceofcontrolledambulatoryBP(62%versus53%,p<.001).Results:Afteramedianfollow-upof5.6yrs,thegroupofsubjectsingesting≥1BP-loweringmedicationsatbedtimeshowedasignificantlylowerrelativeriskoftotalcardiovasculareventsthanthegroupofsubjectsingestingallmedicationsuponawakening(0.39[0.29–0.51];.p<.001).Conclusion:ResultsfromtheprospectiveMAPECstudythusindicatethatbedtimechronotherapywith≥1hypertensionmedications,comparedtoconventionalupon-wakingtreatmentwithallmedications,moreeffectivelyimprovesBPcontrol,betterdecreasestheprevalenceofnon-dippingand,mostimportantly,significantlyreducesCVDmorbidityandmortality.MECHANISMSUNDERLYINGTHEADVANTAGEOFBEDTIMECHRONOTHERAPYUnderusualcircumstances,BPisnormallylowestatnightasissodiumexcretion.However,inacuteandchronicsituationswhensodiumintakeisexcessiveoritsexcretionhamperedduringthedaytime,BPisadjustedbymeansofthepressure/natriuresismechanismtothehigherlevelneededtocompensateovernight,therebyresultinginnon-dipping24hpatterning(Bankiretal.,2008;Fujiietal.,1999;Uzuetal.,2001).

Thepressure-natriuresismechanismandrelationshipismodulatedduringthedaytimebytheeffectsofuprightpostureandactivity,suchthatitismainlyduringthenighttimewhensodiumsensitivity(whichispresentineachperson,buttoadifferentextent)moststronglyexertsitscorrectiveeffects,thusinducingthenon-dippingBPpatterning.Administration-timedifferencesinthePKofBPmedications.Hence,onemightexpecthypertensivemedicationstobeclearedmoreslowlyovernight,therebypotentiallyprolongingtheirdurationofactionwheningestedatbedtimeascomparedtointhemorninguponawakening(Hermidaetal.,2007a).Administration-timedifferencesinthePDofBPmedications,intheabsenceofdifferencesinPK,arealsoknown(seeSmolenskyetal.,2010);theyresultfromcircadianrhythmsincirculatingdrug-freefraction,rate-limitingstepsofkeybiochemicalandmetabolicprocesses,receptornumberandconformation,and/orsecondmessengerandsignalingpathways(Witte&Lemmer,2003).Implications：(i)theconceptof“normotensivenon-dipper,”becausetheCVDriskofthisBPphenotypeishigherthanthatofahypertensivedipperandassuchtheuseoftheterm“normotensive”ismisleadingwiththeconsequentriskofpo