高血压合并多重危险因素及靶器官损害患者的治疗指南葛世俊

高血压合并多重危险因素及靶器官损害患者的治疗指南葛世俊宁波市李惠利医院心内科 BMJ  2003;326:1419 Astrategytoreducecardiovasculardiseasebymorethan80% 减少心血管疾病80%以上的策略  polypill策略:同时针对四种危险因素:lowdensitylipoproteincholesterolbloodpressureserumhomocysteineplateletfunction) 方法:meta-analysesofrandomisedtrialsandcohortstudiesandameta-analysisof15trialsoflowdose(50-125mg/day)aspirin 结果: Polypill组成: 1.astatin(forexample,atorvastatin(dailydose10mg)orsimvastatin(40mg)); 2.threebloodpressureloweringdrugs(forexample,athiazide,ablocker,andanangiotensinconvertingenzymeinhibitor),eachathalfstandarddose; 3.folicacid(0.8mg); 4.aspirin(75mg). 估计:Polypill减少缺血性心脏病88%(84%to91%).减少中风80%(71%to87%). 三分之一55岁或以上人群能得益.平均延长无缺血性心脏病和中风寿命11年.Weestimatethatthecombination(whichwecallthePolypill)reducesIHDeventsby88%(95%confidenceinterval84%to91%)andstrokeby80%(71%to87%).Onethirdofpeopletakingthispillfromage55wouldbenefit,gainingonaverageabout11yearsoflifefreefromanIHDeventorstroke.SummingtheadverseeffectsofthecomponentsobservedinrandomisedtrialsshowsthatthePolypillwouldcausesymptomsin8-15%ofpeople(dependingonthepreciseformulation).MostPatientsHaveOverlappingCVRiskFactorsOfallHypertensives65%havedyslipidemia16%havetype2diabetes45%areoverweight/obeseOfallDyslipidemics48%havehypertension14%havetype2diabetes35%areoverweight/obeseOfallType2Diabetics60%havehypertension60%havedyslipidemia90%areoverweight/obeseHypertensionType2DiabetesDyslipidemiaMultiplecomorbiditiesincreasesrisk400-700% 1 BasedonFraminghamrisk高血压人群中，动脉粥样硬化的发生率更高PreventionandControl(2005)1,3–15PDAY研究(PathobiologicalDeterminantsofAtherosclerosisinYouthStudy)全球15个国家的18个临床中心1277名因外伤死亡的人群（年龄15-34岁）P<0.001P<0.001P<0.0010102030405060胸主动脉腹主动脉右冠状动脉高血压血压正常发生动脉粥样硬化的百分比TheBurdenofCardiovascularDiseaseinWestVirginiaBRFSS(1996)：69.6%高血压患者合并其它危险因素非HTN72.6%HTN27.4%只有HTN30.4%合并危险因素的HTN患者69.6%Hypertension.Overone-fourth(27.4%)ofrespondentstothe1996BRFSSreportedtheyhadbeendiagnosedwithhypertension.Ofthese,30.4%reportednootherCVDriskfactors.Twenty-fourpercent(24.0%)ofhypertensivesalsoreportedaphysicallyinactivelifestyle,while15.1%werebothobeseandphysicallyinactiveinadditiontohavinghypertension.Inall,26.9%ofhypertensivesreportedtwootherCVDriskfactors;2.9%reportedallfour.Figure2.18onthefollowingpagepresentsthebreakdownofpersonswithhypertensionandtheotherCVDriskfactors.REACH注册研究：90.3%的高血压患者合并超过3个危险因素VascularHealthandRiskManagement2007;3(5):587-60344个国家、67,888名年龄≥45岁的患者危险因素包括：接受治疗的糖尿病、糖尿病肾病、无症状的颈动脉狭窄≥70%、收缩压≥150mmHg、接受治疗的高胆固醇血症、吸烟、男性≥55岁、女性≥70岁81.8%高血压90.3%≥3个危险因素LDL-C↑BP↑糖尿病吸烟肥胖多种危险因素共同存在，加速动脉粥样硬化可干预的危险因素不可干预的危险因素年龄↑男性早发家族史氧化应激内皮功能受损，炎症反应高血压患者中，随危险因素增多，心血管风险增加Hypertension.2001;37:1256-1261.男性高血压患者(N=60343)vs.男性非高血压对照者（N=29640)年龄<55岁年龄≥55岁随访时间（年）随访时间（年）存活率（％）存活率（％）无HTNHTN＋0RFHTN＋1-2RFHTN＋≥3RF无HTNHTN＋0RFHTN＋1-2RFHTN＋≥3RFLog-rank=P<0.001Log-rank=P<0.001Abstract—Toevaluatetheriskofcardiovasculardisease(CVD)mortalityinhypertensivemenaccordingtothepresenceofassociatedriskfactors(ARFs).Thepopulationwascomposedof29640normotensivemenwithoutARFs(referencegroup)and60343hypertensivemen(withandwithoutARFs)whohadastandardhealthcheckupattheCentred’InvestigationsPréventivesetCliniquesbetween1978and1988.Mortalitydataforameanperiodof14yearswereanalyzed.ThefollowingARFswereconsidered:totalcholesterol$2.5g/L,personalhistoryofdiabetes,smoking(currentsmokers),bodymassindex.28kg/m2,andheartrate.80bpm.CVDriskrelatedtothepresenceofisolatedhypertension(assessedinhypertensivesubjectswithoutARFsversusthereferencegroup)increasedlinearlyfrom15%attheageof30yearsto134%attheageof80years.Inhypertensivesubjects,oneadditionalARFincreasedCVDriskby56%(47%to65%,P,0.01)inyoungersubjectsbutonlyby4%(28%to17%,P5NS)inoldersubjects.TheroleofhypercholesterolemiaandtobaccosmokinginCVDmortalitywassignificantlyhigherinhypertensivesubjectsaged,55yearsthaninhypertensivesubjectsaged$55years(P,0.01),whereastherolesoftachycardiaandobesitywerenotaffectedbyage.Inyoungerhypertensivesubjects,evaluationofCVDriskandtherapeuticstrategiesshouldtargetARFs.Inoldersubjects,thepresenceofhighbloodpressurelevelsseemstobethemajordeterminantofCVDrisk.Themaincharacteristicsofthedifferentgroups,classifiedaccordingtoageandthepresenceofARFs,arepresentedinTable1.Amongyoungerhypertensivemen,29%hadnoARFs,whereasamongolderhypertensivemen,26%hadnoARFs.Inyoungerhypertensivemen,tobaccosmoking(35.7%),hypercholesterolemia(27.6%),andacceleratedHR(25.5%)werethemostcommonARFs.Inolderhypertensivemen,hypercholesterolemiawasthemostcommonARF(36.2%),followedbysmoking(25.5%).AmongthedifferentARFs,diabetesincreasedthemostwithage(6.8%inyoungerversus14%inolderhypertensivemen)×21×21×20×10多种危险因素共同存在，加剧AS，导致CV事件倍增1008060402002345×22×4×23×8×24×16×25×32相对风险绝对风险(/1,000病例/6年)危险数（糖尿病、高血压、吸烟、CHD家族史、低HDL-C）一级预防多个危险因素同时存在，具有倍增的关系2单个危险因素尽管只是轻中度升高，但若同时存在，也会大幅度增加心血管事件风险3JAMA.1991;265:3255-3264;BMJ.1992;304:405-412;Lancet.1997;350:757-764;Lancet.2001;358:1033-1041.原发事件的风险(%)36251428647586720102030405060708090100SHEP氯噻酮+/-阿替洛尔MRC-OHCTZ+阿替洛尔Syst-Eur尼群地平,依拉普利,HCTZPROGRESS培哚普利+/-利尿剂风险降低(%)没有消除的事件(%)单纯降压，获益远远不够TreatingaSingleRiskFactorisNotEnough:CVRiskRemainsEvenAfterStatinTherapyRiskofPrimaryEvent(%)KasteleinJJP.EurHeartJ.2005;7:F27-F33.Pleaseseeprescribinginformationattheendofthisslidepresentation.MultipleCVRiskManagementResultsinDramaticReductionsinCVD“Attentionshouldbemovedfromknowingone’sBPandcholesterolconcentrationstoknowingone’sabsoluteCVriskanditsdeterminants.” –J.Embersonetal andJacksonetalEmbersonJetal.EurHeartJ.2004;25:484-491.JacksonRetal.Lancet.2005;365:434-441.EmbersonJetal,usedestimatesoftherelativeriskreductionsfrommeta-analysesofrandomisedtrialsincombinationwithdatafromaprospectiveobservationalstudyofCVD(theBritishRegionalHeartStudy)toanalysetheimpactofdifferentriskreductionstrategiesinprimaryprevention.Thestudyexaminedtheeffectsofpreventionstrategiesbasedonsingleriskfactorassessmentortotalriskassessment.Theyconcludedthatassessmentofoverallriskleadstomoreeffectiveinterventionthanassessmentbasedonsingleriskfactors.Furthermore,multipleinterventionshaveconsiderablygreaterbenefitsthaninterventionsbasedontargetingsingleriskfactors.Tenpercentreductionsinlong-termmeanbloodcholesterolandBPcouldhavereducedmajorCVDby45%.JacksonRetal,conductedareviewoftherandomisedtrialsofBPorbloodcholesterolloweringtreatmentsandoutlinedtherationalefortargetingBPandbloodcholesterolloweringtherapytopatientsathighabsoluteCVrisk.TheyconcludedthatseparatemanagementguidelinesforraisedBPandbloodcholesterolneedtobereplacedbyintegratedCVriskmanagementguidelines.TheyalsopositedthatbecauseCVriskfactorsinteractwitheachother,moderatereductionsinseveralriskfactorscanbemoreeffectivethanmajorreductionsinone.高血压的主要治疗目标：最大程度降低心血管疾病总体风险调版式主要终点：非致死性心梗和致死性冠心病012340.00.51.01.52.02.53.03.5随访年数累积事件发生率（％）阿托伐他汀10mg安慰剂p=0.000536%3.3年由于主要终点在很早就出现了非常显著的差异，调脂部分比 计划 项目进度计划表范例计划下载计划下载计划下载课程教学计划下载 提前近2年结束SeverPS,etal,Lancet.2003;361:1149-58ASCOT-LLA：降压基础上，他汀治疗获益显著ASCOT所有病人有高血压伴≥3个CHD危险因素病人伴危险因素比例(%)0102030405060708090100高血压年龄≥55岁男性微量白蛋白尿/蛋白尿吸烟家族CHD史血清TC:HDL-C≥62型糖尿病确认ECG异常LVH先前发生脑血管事件外周血管病847761302724241413116ASCOT研究的病人的危险程度100 多重危险因素干预： 1、治疗性生活方式改变 2、药物：A他汀B阿司匹林2007GuidelinesfortheManagementofArterialHypertension 关于他汀治疗 １、对高血压伴心血管疾病或糖尿病患者应给予他汀治疗。 目标：TC〈4.5mmol/l(175mg/dl)LDL-C〈2.5mmol/l(100mg/dl)Lipidloweringagents†Allhypertensivepatientswithestablishedcardiovasculardiseaseorwithtype2diabetesshouldbeconsideredforstatintherapyaimingatserumtotalandLDLcholesterollevelsof,respectively,,4.5mmol/l(175mg/dl)and,2.5mmol/l(100mg/dl),andlower,ifpossible.2007GuidelinesfortheManagementofArterialHypertension ２、对高血压无明显心血管疾病但高危患者(20%riskofeventsin10years)，即使基线TC和LDL-C水平并不增高，也应给予他汀治疗。 目标：TC<5mmol/l(190mg/dl)LDL-C<3mmol/l(115mg/dl)†Hypertensivepatientswithoutovertcardiovasculardiseasebutwithhighcardiovascularrisk(20%riskofeventsin10years)shouldalsobeconsideredforstatintreatmenteveniftheirbaselinetotalandLDLserumcholesterollevelsarenotelevated.TargetlevelsshouldbeaserumtotalandLDLcholesterolofrespectively5mmol/l(190mg/dl)and3mmol/l(115mg/dl).2007GuidelinesfortheManagementofArterialHypertension 关于抗血小板治疗 １、高血压伴曾发生心血管事件的患者，如无过多出血危险，应给予抗血小板治疗，特别是小剂量阿司匹林Antiplatelettherapy†Antiplatelettherapy,inparticularlow-doseaspirin,shouldbeprescribedtohypertensivepatientswithpreviouscardiovascularevents,providedthatthereisnoexcessiveriskofbleeding.2007GuidelinesfortheManagementofArterialHypertension ２、对高血压无心血管疾病史患者，如年龄大于50岁，伴血清肌酐中度升高或有高心血管危险应考虑小剂量阿司匹林治疗 (serumcreatinine>115mmol/l(1.3mg/dl)) Therefore,treatmentswithalow-doseaspirinhavefavourablebenefit/riskratiosonlyifgiventopatientsaboveacertainthresholdoftotalcardiovascularrisk(15–20%in10years).Low-doseaspirinshouldalsobeconsideredinhypertensivepatientswithoutahistoryofcardiovasculardiseaseifolderthan50years,withamoderateincreaseinserumcreatinineorwithahighcardiovascularrisk.Inalltheseconditions,thebenefit-to-riskratioofthisintervention(reductioninmyocardialinfarctiongreaterthantheriskofbleeding)hasbeenprovenfavourable. Tominimizetheriskofhaemorrhagicstroke,antiplatelettreatmentshouldbestartedafterachievementofBPcontrol.2007GuidelinesfortheManagementofArterialHypertension Subclinicalorgandamage １、LVHACEI,CA,ARB ２、Asympt.atherosclerosis　　CA,ACEI ３、MicroalbuminuriaACEI,ARB ４、RenaldysfunctionACEI,ARB 　　　　　谢谢Weestimatethatthecombination(whichwecallthePolypill)reducesIHDeventsby88%(95%confidenceinterval84%to91%)andstrokeby80%(71%to87%).Onethirdofpeopletakingthispillfromage55wouldbenefit,gainingonaverageabout11yearsoflifefreefromanIHDeventorstroke.SummingtheadverseeffectsofthecomponentsobservedinrandomisedtrialsshowsthatthePolypillwouldcausesymptomsin8-15%ofpeople(dependingonthepreciseformulation).Hypertension.Overone-fourth(27.4%)ofrespondentstothe1996BRFSSreportedtheyhadbeendiagnosedwithhypertension.Ofthese,30.4%reportednootherCVDriskfactors.Twenty-fourpercent(24.0%)ofhypertensivesalsoreportedaphysicallyinactivelifestyle,while15.1%werebothobeseandphysicallyinactiveinadditiontohavinghypertension.Inall,26.9%ofhypertensivesreportedtwootherCVDriskfactors;2.9%reportedallfour.Figure2.18onthefollowingpagepresentsthebreakdownofpersonswithhypertensionandtheotherCVDriskfactors.Abstract—Toevaluatetheriskofcardiovasculardisease(CVD)mortalityinhypertensivemenaccordingtothepresenceofassociatedriskfactors(ARFs).Thepopulationwascomposedof29640normotensivemenwithoutARFs(referencegroup)and60343hypertensivemen(withandwithoutARFs)whohadastandardhealthcheckupattheCentred’InvestigationsPréventivesetCliniquesbetween1978and1988.Mortalitydataforameanperiodof14yearswereanalyzed.ThefollowingARFswereconsidered:totalcholesterol$2.5g/L,personalhistoryofdiabetes,smoking(currentsmokers),bodymassindex.28kg/m2,andheartrate.80bpm.CVDriskrelatedtothepresenceofisolatedhypertension(assessedinhypertensivesubjectswithoutARFsversusthereferencegroup)increasedlinearlyfrom15%attheageof30yearsto134%attheageof80years.Inhypertensivesubjects,oneadditionalARFincreasedCVDriskby56%(47%to65%,P,0.01)inyoungersubjectsbutonlyby4%(28%to17%,P5NS)inoldersubjects.TheroleofhypercholesterolemiaandtobaccosmokinginCVDmortalitywassignificantlyhigherinhypertensivesubjectsaged,55yearsthaninhypertensivesubjectsaged$55years(P,0.01),whereastherolesoftachycardiaandobesitywerenotaffectedbyage.Inyoungerhypertensivesubjects,evaluationofCVDriskandtherapeuticstrategiesshouldtargetARFs.Inoldersubjects,thepresenceofhighbloodpressurelevelsseemstobethemajordeterminantofCVDrisk.Themaincharacteristicsofthedifferentgroups,classifiedaccordingtoageandthepresenceofARFs,arepresentedinTable1.Amongyoungerhypertensivemen,29%hadnoARFs,whereasamongolderhypertensivemen,26%hadnoARFs.Inyoungerhypertensivemen,tobaccosmoking(35.7%),hypercholesterolemia(27.6%),andacceleratedHR(25.5%)werethemostcommonARFs.Inolderhypertensivemen,hypercholesterolemiawasthemostcommonARF(36.2%),followedbysmoking(25.5%).AmongthedifferentARFs,diabetesincreasedthemostwithage(6.8%inyoungerversus14%inolderhypertensivemen)多个危险因素同时存在，具有倍增的关系2单个危险因素尽管只是轻中度升高，但若同时存在，也会大幅度增加心血管事件风险3EmbersonJetal,usedestimatesoftherelativeriskreductionsfrommeta-analysesofrandomisedtrialsincombinationwithdatafromaprospectiveobservationalstudyofCVD(theBritishRegionalHeartStudy)toanalysetheimpactofdifferentriskreductionstrategiesinprimaryprevention.Thestudyexaminedtheeffectsofpreventionstrategiesbasedonsingleriskfactorassessmentortotalriskassessment.Theyconcludedthatassessmentofoverallriskleadstomoreeffectiveinterventionthanassessmentbasedonsingleriskfactors.Furthermore,multipleinterventionshaveconsiderablygreaterbenefitsthaninterventionsbasedontargetingsingleriskfactors.Tenpercentreductionsinlong-termmeanbloodcholesterolandBPcouldhavereducedmajorCVDby45%.JacksonRetal,conductedareviewoftherandomisedtrialsofBPorbloodcholesterolloweringtreatmentsandoutlinedtherationalefortargetingBPandbloodcholesterolloweringtherapytopatientsathighabsoluteCVrisk.TheyconcludedthatseparatemanagementguidelinesforraisedBPandbloodcholesterolneedtobereplacedbyintegratedCVriskmanagementguidelines.TheyalsopositedthatbecauseCVriskfactorsinteractwitheachother,moderatereductionsinseveralriskfactorscanbemoreeffectivethanmajorreductionsinone.调版式Lipidloweringagents†Allhypertensivepatientswithestablishedcardiovasculardiseaseorwithtype2diabetesshouldbeconsideredforstatintherapyaimingatserumtotalandLDLcholesterollevelsof,respectively,,4.5mmol/l(175mg/dl)and,2.5mmol/l(100mg/dl),andlower,ifpossible.†Hypertensivepatientswithoutovertcardiovasculardiseasebutwithhighcardiovascularrisk(20%riskofeventsin10years)shouldalsobeconsideredforstatintreatmenteveniftheirbaselinetotalandLDLserumcholesterollevelsarenotelevated.TargetlevelsshouldbeaserumtotalandLDLcholesterolofrespectively5mmol/l(190mg/dl)and3mmol/l(115mg/dl).Antiplatelettherapy†Antiplatelettherapy,inparticularlow-doseaspirin,shouldbeprescribedtohypertensivepatientswithpreviouscardiovascularevents,providedthatthereisnoexcessiveriskofbleeding.Low-doseaspirinshouldalsobeconsideredinhypertensivepatientswithoutahistoryofcardiovasculardiseaseifolderthan50years,withamoderateincreaseinserumcreatinineorwithahighcardiovascularrisk.Inalltheseconditions,thebenefit-to-riskratioofthisintervention(reductioninmyocardialinfarctiongreaterthantheriskofbleeding)hasbeenprovenfavourable.