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 1 2 3 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 Bothstudiesfoundthattheeveningdrugadministrationschedulereducedtheincidenceofthenon dippingBPpatternamongtreatedhypertensivepatients Furthermore theHOPEtrialdemonstratedthatthetreatment conferrednormalizationofthe24 hBPdippingpatternwasassociatedwithalowerincidenceofstrokeandmyocardialinfarctionrelativetothosedisplayingtheabnormalnon dipperpattern However themajorshortcomingofboththeSyst EurandHOPEtrialsisthateachwasdevoidofacomparisontreatmentgrouprandomizedtomorningtherapy SmolenskyMH HermidaRC AyalaDE andetal Administration time dependenteffectsofbloodpressure loweringmedications basisforthechronotherapyofhypertension J BloodPressMonit 2010 15 173 180 THEMAPECSTUDY HYPERTENSIONCHRONOTHERAPYANDCVDRISK Atotalof2156hypertensivesubjectswereevaluatedby48 hABPMatbase lineandwithidenticalassessmentconductedannually ormorefrequently quarterly ifadjustmentoftreatmentwasrequired Atbaseline thetwotreatment timegroupsweremostlycomparableintermsoftheirclinicandmeanambulatorySBPandDBPandprevalenceofnon dippingBPpattern FrancescoPortaluppi MichaelH Smolensky PERSPECTIVESONTHECHRONOTHERAPYOFHYPERTENSIONBASEDONTHERESULTSOFTHEMAPECSTUDY J ChronobiologyInternational 2010 27 8 1652 1667 Monitorizaci nAmbulatoriaparaPredicci ndeEventosCardiovasculares 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 MECHANISMSUNDERLYINGTHEADVANTAGEOFBEDTIMECHRONOTHERAPY Underusualcircumstances 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 ismisleadingwiththeconsequentriskofpoorpatientmanagement ii theconceptualapproachtotreatmentthatentailsachievingthehomeostaticgoalofconstantorrelativelyinvariableeffectofBP loweringthroughoutthe24 hdosingintervalusingonce a daymedicationsofhigh smoothnessindex whichappearsquestionable evencontraindicated inthecaseofnon dipperpatients and iii therelianceonc