糖尿病患之高血壓癥課件

糖尿病患之高血壓癥國立成功大學(xué)醫(yī)學(xué)院附設(shè)醫(yī)院內(nèi)科部內(nèi)分泌新陳代謝科吳達(dá)仁醫(yī)師糖尿病患之高血壓癥國立成功大學(xué)醫(yī)學(xué)院附設(shè)醫(yī)院1DiabetesandHypertensionHypertensionoccurswithtwicethefrequencyinthediabeticpopulationascomparedwiththegeneral,non-diabeticpopulation.50%ofpatientsdiagnosedwithdiabeteseventuallybecomehypertensive.ChristliebAR.Diabetes1981：30(Suppl2):90Theage-andsex-adjustedprevalenceofhypertensionamongdiabeticsubjectswastwicethatofnon-diabeticsubjects(39.6%vs16.4%)inTAIWAN.2.Hypertensivesubjectshadahigherprevalenceofdiabetesthannormotensivesubjects(10.2%vs4.9%).TaiTY,etal.DiabetesCare1991:14:1031.T-JWUDiabetesandHypertensionHyper2高血壓病患有較高的糖尿病發(fā)生率追蹤之8年發(fā)生率

(每1000人年發(fā)生案例)GressTWetal.NEnglJMed.2000;342:905-912.正常血壓n=8746高血壓n=3804T-JWU高血壓病患有較高的糖尿病發(fā)生率追蹤之8年發(fā)生率Gress3糖尿病患之高血壓癥課件4糖尿病患之高血壓癥課件5糖尿病與收縮高血壓癥：增加心血管病風(fēng)險(xiǎn)每1000人-年發(fā)生心血管病事件1.SHEPCooperativeResearchGroup.JAMA.1991;265:3255-3264.2.StaessenJAetal.Lancet.1997;350:1757-1764.3.WangJGetal.ArchInternMed.2000;160:221-228.SHEP1SYST-EUR2SYST-CHINA3糖尿病與收縮高血壓癥：增加心血管病風(fēng)險(xiǎn)每1000人-年發(fā)生16高血壓在糖尿病病患的重要性高血壓是糖尿病患極為常見之共犯結(jié)構(gòu)。約20–60%糖尿病患患有高血壓。在第2型糖尿病患之高血壓，經(jīng)常是以胰島素抗性為特徵之代謝癥候群(metabolicsyndrome)的主要成員之一。在第1型糖尿病患之高血壓則經(jīng)常是反應(yīng)著糖尿病腎臟病變(diabetic

nephropathy)的開始。高血壓會增加糖尿病患大血管併發(fā)癥(macrovascular)與微細(xì)血管併發(fā)癥(microvascularcomplications)之風(fēng)險(xiǎn)包括腦卒中、冠心病、週邊血管病變、網(wǎng)膜病變、及腎臟病變。由最近幾年累積下來嚴(yán)謹(jǐn)?shù)腞CT(randomizedclinical

trials)資料証實(shí)：積極治療糖尿病患之高血壓是可以改善大血管與微細(xì)血管病變。T-JWU高血壓在糖尿病病患的重要性高血壓是糖尿病患極為常見之共犯結(jié)構(gòu)7降低血壓有助減低糖尿病相關(guān)併發(fā)癥之風(fēng)險(xiǎn)

嚴(yán)密控制血壓(144/82mmHg)相對於一般血壓控制(154/87mmHg)減低糖尿病相關(guān)併發(fā)癥風(fēng)險(xiǎn)之比率其功效甚於降血糖(HbA1c由7.9%降至7%)

降血壓降血糖 -32%*

10% -24%**

12% -44%*

NA -56%*

NA

-37%*

25%UKProspectiveDiabetesStudyGroup.BMJ.1998;317:703-713.糖尿病相關(guān)死亡

糖尿病相關(guān)併發(fā)癥

腦卒中(Stroke)心臟衰竭(Heartfailure)糖尿病微細(xì)血管併發(fā)癥T-JWU降低血壓有助減低糖尿病相關(guān)併發(fā)癥之風(fēng)險(xiǎn) 嚴(yán)密控制血壓(14805101520253010510095908580達(dá)成之舒張壓

mmHg%危險(xiǎn)性減少HOTStudy

理想的舒張壓HOTStudy顯示降血壓可降低心血管意外之危險(xiǎn)性達(dá)30%

Hanssonetal199805101520253010510095908580達(dá)成之舒90510152025￡90￡85￡80mmHg

目標(biāo)舒張壓重大心血管意外/1000病人/年Hanssonetal1998p=0.005fortrend糖尿病人積極降血壓可有效降低

之心血管意外(HOTStudy)0510152025￡90￡85￡80mmHg

目標(biāo)舒張壓10平均舒張壓基礎(chǔ)腎臟功能與重大心血管意外和舒張壓間之關(guān)係JHypertens1999;17(Suppl3):S1460510152025303540757080859095100105理想舒張壓:Highcreatinine=71.9mmHgLowcreatinine=80.9mmHg重大心血管意外/1000病人/年Creatinine>1.5mg/dlCreatinine1.5mg/dl平均舒張壓基礎(chǔ)腎臟功能與重大心血管意外和舒張壓間之關(guān)係JH11糖尿病患血壓目標(biāo)值之實(shí)證WorkingGrouponHypertensionin定140/90mmHg為糖尿病患目標(biāo)血壓

。JNCVI,1997

定130/85mmHg為糖尿病患目標(biāo)血壓。

125/75

mmHg為蛋白尿(>1g/day)病患目標(biāo)血壓。UKPDS與HypertensionOptimalTreatment(HOT)研究，兩者皆顯示以血壓<130/80mmHg為目標(biāo)值的治療成效，確實(shí)顯著優(yōu)於較寬鬆目標(biāo)值的治療。由流行病學(xué)研究資料顯示糖尿病患血壓120/70mmHg

以上，就與心血管事件以及死亡率增加息息相關(guān)。因此，在無特殊安全顧慮下，設(shè)定血壓目標(biāo)值<130/80mmHg是合理的。

T-JWU糖尿病患血壓目標(biāo)值之實(shí)證WorkingGrouponH12高血壓病患非藥物治療之實(shí)證(一)減肥減肥不但可降低血壓、也可改善血糖與血脂肪。每減肥1kg大約可降低血壓1mmHg。此作用與鈉攝取量無關(guān)。極低熱量飲食(VLCD)與藥物治療介入糖尿病患高血壓的角色仍然未充分研究。有些厭食劑可能致血壓升高，反而須要特別注意。中度限鈉飲食本態(tài)性高血壓患者中度限鈉飲食在降低血壓方面是確有療效的。中度限鈉飲食(每日限鈉由2.3g)，本態(tài)性高血壓大約可降低縮收舒張血壓5mmHg，降低舒張血壓2-3mmHg。doseresponseeffect”。限鈉飲食用於高血壓之糖尿病患族群，雖然廣泛應(yīng)用，尚待確認(rèn)。高血壓病患非藥物治療之實(shí)證(一)減肥13高血壓病患非藥物治療之實(shí)證(二)體能活動中度強(qiáng)化體能活動(如：儘可能每天快步30-45分鐘)在降低血壓是確有療效的。35歲或以上病患，執(zhí)行激烈體能運(yùn)動計(jì)劃時(shí)，必須有先行運(yùn)動壓力測試或其他適當(dāng)非侵襲性測試。而一般無癥狀病人以中度體能活動，一般不須先行運(yùn)動壓力測試。其他建議JNC6建議抽煙必須戒掉；酒須適量。這些建議也應(yīng)適用於糖尿病患。高血壓病患非藥物治療之實(shí)證(二)體能活動14StudyAgentPatientsAgeFollow-upChangeinBPInitialBPABCDEnalaprilNisodipine23523557.757.75NA156/98155/98FACETFosinoprilAmlodipine18919162.863.83.513/819/8170/95171/94HOTFelodipine150161.53.829.9/24.3170/105CAPPPCaptoprilB-blocker/Diuretic30926355.055.76.116/1016/10163.6/97.1163.3/97.3SHEPChlorthalidonePlacebo28330070.270.559.8/2.2170.2/72.9170.2/74.8Syst-EurNitredipinePlacebo252240≧60≧6028.6/3.8175.3/84.5BrilliantLisinoprilNifedipine167168≦75≦75116/1111/9163/99161/97MICRO-HOPERamiprilplacebo18081769≧554.52.4/1.0141.7142.3UKPDSCaptoprilAtenololPlacebo40035839056.356.056.58.49/410/5159/94159/93160/94糖尿病之高血壓之大型治療研究StudyAgentPatientsAgeFollow-up15SHEP研究中283位併單獨(dú)收縮高血壓之糖尿病患以Diuretic治療之效果風(fēng)險(xiǎn)減少(%)CurbJDetal.JAMA.1996;276:1886-1892.0-10-20-30-40-50-60T-JWU主要CV事件腦卒中心肌梗塞全數(shù)死亡率SHEP研究中283位併單獨(dú)收縮高血壓之糖尿病患以Diure16UKPDSBPControlStudy:

TightvsLessTightControlChangesinSBPandDBP801001201401600123456789Bloodpressure(mmHg)YearsfromrandomizationSystolicbloodpressureDiastolicbloodpressureLesstightTightLesstightTightLesstightcontrolStart160/94mmHgFinish154/87mmHgTightcontrolStart161/94mmHgFinish144/82mmHg

UKPDSGroup.BMJ.1998;317:703-713.T-JWUUKPDSBPControlStudy:

Tight170.2

Anydiabetes-relatedendpoint 50.9 67.4

Deathsrelatedtodiabetes 13.7 20.3

All-causemortality 22.4 27.2

Myocardialinfarction 18.6 23.5

Stroke 6.5 11.6

Peripheralvasculardisease 1.4 2.7

Microvasculardisease 12.0 19.2

UKPDSBPControlStudy:

AbsoluteandRelativeRiskDecreased

riskIncreased

riskLesstightcontrolTightcontrolUKPDSGroup.BMJ.1998;317:703-713.Favors

tightcontrolFavorsless

tightcontrolAbsoluterisk

(eventsper1000patient-years)Relativerisk*(95%CI)*Vslesstightcontrol.150.2 UKPDSBPControlStudy:

18Bloodpressure(mmHg)UKPDSBPControlStudy:

ACEInhibitorvsβ-blocker

608010014016018002468Cohort,MeanValuesYearsfromrandomizationSystolicbloodpressureDiastolicbloodpressureTherewerenodifferencesinBP-loweringefficacybetweenanACEinhibitor(captopril)anda-blocker(atenolol).Lesstightcontrol

ACEinhibitor

-blockerUKPDSGroup.BMJ.1998;317:713-720.T-JWUBloodpressure(mmHg)UKPDSBP19

AnACEinhibitor(captopril)andaα-blocker(atenolol)reducedtheriskofdiabeticcomplicationstoasimilarextent*95%CIforallvalues,except99%CIforretinopathyand

albuminuria;?2-stepchange.1.101.271.140.430.280.44Anydiabetes-relatedendpointDiabetes-relateddeathsAll-causemortalityRR

P

value1.201.121.290.350.740.30MyocardialinfarctionStrokeMicrovasculardiseaseRetinopathyprogressionat7.5y? 0.91 0.28Urinealbumin>50mg/Lat9y 1.21 0.31Urinealbumin>300mg/Lat9y 0.48 0.09Relative

risk*(95%CI)Favors

ACEinhibitorFavors

-blocker0.512UKPDSGroup.BMJ.1998;317:713-720.UKPDSBPControlStudy:

ACEInhibitorvsβ-BlockerT-JWUAnACEinhibitor(captopril)20以血管張力素轉(zhuǎn)化酵素抑制劑治療高血壓之糖尿病患的效果風(fēng)險(xiǎn)減少(%)HOPEstudyinvestigators.Lancet.2000;355:253-259.0-10-20-30-40心肌梗塞腦卒中CV死亡率明顯腎病變T-JWU以血管張力素轉(zhuǎn)化酵素抑制劑治療高血壓之糖尿病患的效果風(fēng)險(xiǎn)減少21EffectsofACEIonBPinHypertensiveType2DiabeticswithIncipientNephropathy

BRILLIANTAgardhC-D,etal.JHumHypertens1996;10:185-192LisinoprilNifedipine18016014012010080SittungBP(mmHg)MonthofTreatment0136912EffectsofACEIonBPinHyper22EffectsofACEIonUrinaryAlbuminExcretioninHypertensiveType2DiabeticswithIncipientNephropathyAgardhC-D,etal.JHumHypertens1996;10:185-192LisinoprilNifedipine[p<0.0006vs.placeboat12months]T-JWUAlbuminExcretion(μg/min)Baseline6month12month70605040302010BRILLIANTEffectsofACEIonUrinaryAlb23ACEIImprovesAlbuminExcretionRateinMicroalbuminuricPatientswithT1DM：

EUrodiabControlledtrialofLisinoprilinInsulin

dependentDiabetes(EUCLID)

EUCLIDStudyGroup.Lancet1997;349:1787-1792AER(μg/min)Time(months)706050403020106121824PlaceboLisinoprilTreatmentdifference=38.5μg/min,p=0.001T-JWUACEIImprovesAlbuminExcretio24MalaiseandfatigueEdemaGItractDiseases

RenalFailure

Cough

ErectiledysfunctionHeadacheDepressionRashAllergicreaction

Intermittentclaudication

BronchospasmColdandnumbhandHypokalemiaHyponatremia)

SideEffectACEICCBDiureticsβ-blockersNo.(%)(n=635)(n=235)(n=283)(n=358)高血壓糖尿病患降血壓治療之主要不良反應(yīng)DataSources:ACEI:ABCD,UKPDS;CCB:ABCD;Diuretics:SHEP;β-blockers:UKPDSTJWU21(3.3)11(1.7)9(1.4)6(0.9)29(4.6)3(0.5)2(0.3)1(0.2)1(0.2)7(1.1)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)20(8.5)4(1.7)2(0.9)8(3.4)2(0.9)10(4.3)0(0.0)1(0.4)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)13(4.6)0(0.0)34(11.9)0(0.0)11(3.9)0(0.0)0(0.0)0(0.0)0(0.0)70(24.8)6(2.3)22(7.9)16(4.5)0(0.0)5(1.4)0(0.0)0(0.0)

6(1.7)3(0.8)1(0.3)0(0.0)2(0.6)15(4.2)22(6.2)0(0.0)0(0.0)0(0.0)MalaiseandfatigueSideEffect25DiureticBeta-blockersACEinhibitorCCBAlpha-blockers血糖↑↑中性中性中性血脂肪↑↑中性中性中性電解質(zhì)干擾中性中性中性中性胰島素抗性↑↑↓中性↓併發(fā)癥冠心病保護(hù)(A)保護(hù)(A)保護(hù)(A)未評未定腎病變未評保護(hù)(A)保護(hù)(A)保護(hù)*(C)未評腦卒中保護(hù)(A)保護(hù)(A)保護(hù)(A)保護(hù)*(A)未評降血壓藥物對高血壓糖尿病患之影響DiureticBeta-blockersACEinhib26NephroprotectiveRoleofAngiotensinIIReceptorAntagonistsinType2DiabetesTheIrbesartanDiabeticNephropathyTrial(IDNT)andtheReductionofEndpointsinNIDDMwithAngiotensinIIAntagonistLosartan(RENAAL)trial.Bothtrialsshowedasignificantreductionintheprimarypre-specifiedend-pointofdeath,orworseningofrenalfunction(doublingofserumcreatinine)orthedevelopmentofend-stagerenaldisease.TheIrbesartanMicroalbuminuriaStudy(IRMA)-2andtheMicroalbuminuriaReductionwithValsartanstudy(MARVAL)-weretrialsconductedinpatientswithtype2diabeteswithmicroalbuminuria.Thesetrialsdemonstratedanangiotensinreceptorblocker(ARB)interferewiththenaturalhistoryofdiabeticnephropathyinabloodpressure-independentfashion.NephroprotectiveRoleofAngio27TheEffectofIrbesartanonTheDevelopmentofDiabeticNephropathyinPatientswithT2DMOnsetofDiabetic

Nephropathy(%)Relative

risk*(95%CI)FavorsARBs0.51210/19419/19530/201300mg/dayP<0.001150mg/dayP=0.081Placebo150mg300mg/day/day20161284ParvingHH,etal.NEnglJMed.2001;345:870-8.T-JWUTheEffectofIrbesartanonTh28糖尿病病患併高血壓之藥物治療實(shí)證(甲)Inpatients

witheithermildormoreseverehypertensionandinbothtype

1andtype2diabetes,theestablishedpracticeofchoosing

anACEinhibitorasthefirst-lineagentinmostpatientswith

diabetesisreasonable.(A)Inpatientswithmicroalbuminemiaor

clinicalnephropathy,bothACEinhibitors(type1andtype2

patients)and

ARBs(type2patients)areconsideredfirst-line

therapyforthepreventionofandprogressionofnephropathy.(A)

Diureticand?-blocker–based

therapyarealsosupportedbyevidence(A).DCCBsshould

beusedassecond-linedrugs.(A)Otherclasses,including

α-blockers,maybeusedunderspecificindications.T-JWU糖尿病病患併高血壓之藥物治療實(shí)證(甲)Inpatient29AllpatientswithDMandHTNshouldbe

treated

witharegimenthatincludeseitheranACEI

orARB.

Ifoneclassisnottolerated,theothershouldbesubstituted.

Ifneededtoachievebloodpressuretargets,athiazidediuretic

shouldbeadded.(E)IfACEinhibitorsorARBsareused,monitor

renalfunctionand

serumpotassiumlevels.(E)

Thereisclinicaltrialsupportforeach

ofthefollowing

statements:Inpatientswithtype1diabetes

withhypertension

andanydegree

ofalbuminuria,ACEinhibitors

havebeenshown

todelaythe

progressionofnephropathy.(A)

Inpatientswith

type2diabetes,hypertension,andmicroalbuminuria,

ACEinhibitors

andARBshavebeenshowntodelaytheprogression

tomacroalbuminuria.

(A)

Inthosewithtype2diabetes,hypertension,

macroalbuminuria

(>300mg/day),andrenalinsufficiency,

anARBshouldbe

stronglyconsidered.(A)

糖尿病病患併高血壓之藥物治療實(shí)證(乙)T-JWUAllpatientswithDMandHTNs300.5EffectsofARBsonCardiovascularEventsandRenalDiseaseinT2DMSiebenhoferA,etal.DiabetMed2004;21:18-25.FavorsARBsFavorsStandardOddsratio(95%CI)12TotalmortalityCombinedCardiovasxccularevents

CombinedEnd-stagerenaldiseaseCombinedLewisLindholmLewisLindholmLewis0.5FavorsARBsOddsratio(95%CI)12FavorsPlaceboBrennerLewisBrennerLewisBrennerLewisT-JWU0.5EffectsofARBsonCardiova31ARBandRenalDiseaseinPatientsWithType2Diabetes

AnAsianperspectivefromtheRENAALstudyAtotalof252Asianpatients

wereenrolledintheRENAALstudy,whichcomparedlosartantoplaceboinadditiontoconventional

antihypertensivemedicationsintype2diabeticpatientswith

nephropathy.Meanfollow-upwas3.2years.Losartanreducedtheriskoftheprimarycomposite

endpointcomposedofadoublingofserumcreatinine,end-stage

renaldisease,orall-causemortalityinAsianpatients

by35%

(P=0.02).Nodifferencebetweenlosartanandplacebowasobservedforthecardiovascularcompositeoutcomes.

Losartanreduced

thelevelofproteinuriaby47%(P<0.001)andrateofdecrease

inrenalfunctionby31%(P=0.0074).ChanJC,etalDiabetesCare2004:27:874-879.ARBandRenalDiseaseinPatie32中危險(xiǎn)層級超高或高危險(xiǎn)層級低危險(xiǎn)層級監(jiān)測血壓與危險(xiǎn)因素3-6個(gè)月監(jiān)測血壓與危險(xiǎn)因素6-12個(gè)月立即藥物治療收縮壓140或舒張壓90開始藥物治療收縮壓150或舒張壓95開始藥物治療未超出則繼續(xù)監(jiān)測未超出則繼續(xù)監(jiān)測高血壓處理對策生活型態(tài)調(diào)整:戒煙,減肥,適酒量,限鹽,運(yùn)動等依危險(xiǎn)因子,靶器官受損,與關(guān)聯(lián)狀況評估危險(xiǎn)層級1999WHO-ISHHYPERTENSIONPRACTICEGUIDELINESFORPRIMARYCAREPHYSICIANS中危險(xiǎn)層級超高或高低危險(xiǎn)層級監(jiān)測血壓與監(jiān)測血壓與立即藥物治療33ClassificationandManagementofBPforadults(JNC7)BPclassification

SBP*mmHg

DBP*mmHg

Lifestylemodification

Initialdrugtherapy

WithoutcompellingindicationWithcompellingindicationsNormal

<120

and<80

Encourage

Prehypertension

120–139

or80–89

Yes

Noantihypertensivedrugindicated.

Drug(s)forcompellingindications.?

Stage1Hypertension

140–159

or90–99

Yes

Thiazide-typediureticsformost.MayconsiderACEI,ARB,BB,CCB,orcombination.

Drug(s)forthecompellingindications.?Otherantihypertensivedrugs(diuretics,ACEI,ARB,BB,CCB)asneeded.Stage2Hypertension

>160

or>100

Yes

Two-drugcombinationformost?(usuallythiazide-typediureticandACEIorARBorBBorCCB).

*TreatmentdeterminedbyhighestBPcategory.?Initialcombinedtherapyshouldbeusedcautiouslyinthoseatriskfororthostatichypotension.?TreatpatientswithchronickidneydiseaseordiabetestoBPgoalof<130/80

mmHg.ClassificationandManagement34Startingat115/75mmHg,CVDriskdoubleswitheachincrementof20/10mmHgthroughouttheBPrange.ThosewithSBP120–139mmHgorDBP80–89mmHgshouldbeconsidered

prehypertensive.Thiazide-typediureticsshouldbeinitialdrugtherapyformost,eitheraloneorcombinedwithotherdrugclasses.MostpatientswillrequiretwoormoreantihypertensivedrugstoachievegoalBP.IfBPis>20/10mmHgabovegoal,initiatetherapywith2agents.Certainhigh-riskconditionsarecompellingindicationsforotherdrugclasses.

SomeMessagesfromJNC7Startingat115/75mmHg,CVDr35美國糖尿病學(xué)會對糖尿病人血壓控制的建議(ADA2004)目標(biāo)血壓應(yīng)控制在收縮壓小於130mmHg、舒張壓小於80mmHg。收縮壓於130–139mmHg、或舒張壓於80–90mmHg的糖尿病病人，經(jīng)3個(gè)月非藥物療法的行為介入治療未達(dá)目標(biāo)血壓，也即須加上降血壓藥物治療。收縮壓≧140mmHg、或舒張壓≧90mmHg的糖尿病病人，非藥物療法的行為介入治療同時(shí)，也須即加上降血壓藥物治療。ADApositionstatement.DiabetesCare2004;27(suppl1):565-7美國糖尿病學(xué)會對糖尿病人血壓控制的建議(ADA2004)36美國糖尿病學(xué)會對糖尿病抗高血壓藥物治療的建議血管張力素轉(zhuǎn)化酵素抑制劑(ACE-Is)、血管張力素接受器阻斷劑(ARBs)、乙型阻斷劑(β-blockers)、或利尿劑(Diuretics)均可做起始治療的選項(xiàng)。大多數(shù)的糖尿病患要控制到理想血壓之目標(biāo)，兩種以上的降血壓藥物並用是不能少的；須要三種以上的降血壓藥物並用也很常見。大多數(shù)的糖尿病患，尤其具其他危險(xiǎn)因子，不論高血壓輕重，不論第1、2型，建議以ACE-Is為首選藥物。對併糖尿病腎病變(顯微蛋白尿或蛋白尿)，ACE-Is(第1、2型)與ARBs(第2型)皆可減少尿蛋白排出量，可延緩腎功能的惡化。所以均被推薦為首選藥物。如果糖尿病患合併近期心肌梗塞，加上β-blockers，可減少心血管併發(fā)癥死亡率。長效型鈣離子通道阻斷劑也是可用的，一般作二線使用。糖尿病抗高血壓藥物治療，須考慮comorbidities,tolerability,personalpreferences,andcost。PositionStatementofADA.DiabetesCare2004;27:S565-7美國糖尿病學(xué)會對糖尿病抗高血壓藥物治療的建議血管張力素轉(zhuǎn)化酵37CostofACEI

orARBTherapyinTaiwanCapoten259.3Tritace2.520.8Zestrii1018.0Renitec1020.5Renitec2020.5Acertil424.9Coraar5027.6Diovan8027.1Aprovel15027.6Micardis4027.6T-JWUACEIDoseCostARBsDoseCostCostofACEIorARBTherapy38Thankyouforyourattention!!Thankyouforyourattention!39糖尿病患之高血壓癥國立成功大學(xué)醫(yī)學(xué)院附設(shè)醫(yī)院內(nèi)科部內(nèi)分泌新陳代謝科吳達(dá)仁醫(yī)師糖尿病患之高血壓癥國立成功大學(xué)醫(yī)學(xué)院附設(shè)醫(yī)院40DiabetesandHypertensionHypertensionoccurswithtwicethefrequencyinthediabeticpopulationascomparedwiththegeneral,non-diabeticpopulation.50%ofpatientsdiagnosedwithdiabeteseventuallybecomehypertensive.ChristliebAR.Diabetes1981：30(Suppl2):90Theage-andsex-adjustedprevalenceofhypertensionamongdiabeticsubjectswastwicethatofnon-diabeticsubjects(39.6%vs16.4%)inTAIWAN.2.Hypertensivesubjectshadahigherprevalenceofdiabetesthannormotensivesubjects(10.2%vs4.9%).TaiTY,etal.DiabetesCare1991:14:1031.T-JWUDiabetesandHypertensionHyper41高血壓病患有較高的糖尿病發(fā)生率追蹤之8年發(fā)生率

(每1000人年發(fā)生案例)GressTWetal.NEnglJMed.2000;342:905-912.正常血壓n=8746高血壓n=3804T-JWU高血壓病患有較高的糖尿病發(fā)生率追蹤之8年發(fā)生率Gress42糖尿病患之高血壓癥課件43糖尿病患之高血壓癥課件44糖尿病與收縮高血壓癥：增加心血管病風(fēng)險(xiǎn)每1000人-年發(fā)生心血管病事件1.SHEPCooperativeResearchGroup.JAMA.1991;265:3255-3264.2.StaessenJAetal.Lancet.1997;350:1757-1764.3.WangJGetal.ArchInternMed.2000;160:221-228.SHEP1SYST-EUR2SYST-CHINA3糖尿病與收縮高血壓癥：增加心血管病風(fēng)險(xiǎn)每1000人-年發(fā)生145高血壓在糖尿病病患的重要性高血壓是糖尿病患極為常見之共犯結(jié)構(gòu)。約20–60%糖尿病患患有高血壓。在第2型糖尿病患之高血壓，經(jīng)常是以胰島素抗性為特徵之代謝癥候群(metabolicsyndrome)的主要成員之一。在第1型糖尿病患之高血壓則經(jīng)常是反應(yīng)著糖尿病腎臟病變(diabetic

nephropathy)的開始。高血壓會增加糖尿病患大血管併發(fā)癥(macrovascular)與微細(xì)血管併發(fā)癥(microvascularcomplications)之風(fēng)險(xiǎn)包括腦卒中、冠心病、週邊血管病變、網(wǎng)膜病變、及腎臟病變。由最近幾年累積下來嚴(yán)謹(jǐn)?shù)腞CT(randomizedclinical

trials)資料証實(shí)：積極治療糖尿病患之高血壓是可以改善大血管與微細(xì)血管病變。T-JWU高血壓在糖尿病病患的重要性高血壓是糖尿病患極為常見之共犯結(jié)構(gòu)46降低血壓有助減低糖尿病相關(guān)併發(fā)癥之風(fēng)險(xiǎn)

嚴(yán)密控制血壓(144/82mmHg)相對於一般血壓控制(154/87mmHg)減低糖尿病相關(guān)併發(fā)癥風(fēng)險(xiǎn)之比率其功效甚於降血糖(HbA1c由7.9%降至7%)

降血壓降血糖 -32%*

10% -24%**

12% -44%*

NA -56%*

NA

-37%*

25%UKProspectiveDiabetesStudyGroup.BMJ.1998;317:703-713.糖尿病相關(guān)死亡

糖尿病相關(guān)併發(fā)癥

腦卒中(Stroke)心臟衰竭(Heartfailure)糖尿病微細(xì)血管併發(fā)癥T-JWU降低血壓有助減低糖尿病相關(guān)併發(fā)癥之風(fēng)險(xiǎn) 嚴(yán)密控制血壓(144705101520253010510095908580達(dá)成之舒張壓

mmHg%危險(xiǎn)性減少HOTStudy

理想的舒張壓HOTStudy顯示降血壓可降低心血管意外之危險(xiǎn)性達(dá)30%

Hanssonetal199805101520253010510095908580達(dá)成之舒480510152025￡90￡85￡80mmHg

目標(biāo)舒張壓重大心血管意外/1000病人/年Hanssonetal1998p=0.005fortrend糖尿病人積極降血壓可有效降低

之心血管意外(HOTStudy)0510152025￡90￡85￡80mmHg

目標(biāo)舒張壓49平均舒張壓基礎(chǔ)腎臟功能與重大心血管意外和舒張壓間之關(guān)係JHypertens1999;17(Suppl3):S1460510152025303540757080859095100105理想舒張壓:Highcreatinine=71.9mmHgLowcreatinine=80.9mmHg重大心血管意外/1000病人/年Creatinine>1.5mg/dlCreatinine1.5mg/dl平均舒張壓基礎(chǔ)腎臟功能與重大心血管意外和舒張壓間之關(guān)係JH50糖尿病患血壓目標(biāo)值之實(shí)證WorkingGrouponHypertensionin定140/90mmHg為糖尿病患目標(biāo)血壓

。JNCVI,1997

定130/85mmHg為糖尿病患目標(biāo)血壓。

125/75

mmHg為蛋白尿(>1g/day)病患目標(biāo)血壓。UKPDS與HypertensionOptimalTreatment(HOT)研究，兩者皆顯示以血壓<130/80mmHg為目標(biāo)值的治療成效，確實(shí)顯著優(yōu)於較寬鬆目標(biāo)值的治療。由流行病學(xué)研究資料顯示糖尿病患血壓120/70mmHg

以上，就與心血管事件以及死亡率增加息息相關(guān)。因此，在無特殊安全顧慮下，設(shè)定血壓目標(biāo)值<130/80mmHg是合理的。

T-JWU糖尿病患血壓目標(biāo)值之實(shí)證WorkingGrouponH51高血壓病患非藥物治療之實(shí)證(一)減肥減肥不但可降低血壓、也可改善血糖與血脂肪。每減肥1kg大約可降低血壓1mmHg。此作用與鈉攝取量無關(guān)。極低熱量飲食(VLCD)與藥物治療介入糖尿病患高血壓的角色仍然未充分研究。有些厭食劑可能致血壓升高，反而須要特別注意。中度限鈉飲食本態(tài)性高血壓患者中度限鈉飲食在降低血壓方面是確有療效的。中度限鈉飲食(每日限鈉由2.3g)，本態(tài)性高血壓大約可降低縮收舒張血壓5mmHg，降低舒張血壓2-3mmHg。doseresponseeffect”。限鈉飲食用於高血壓之糖尿病患族群，雖然廣泛應(yīng)用，尚待確認(rèn)。高血壓病患非藥物治療之實(shí)證(一)減肥52高血壓病患非藥物治療之實(shí)證(二)體能活動中度強(qiáng)化體能活動(如：儘可能每天快步30-45分鐘)在降低血壓是確有療效的。35歲或以上病患，執(zhí)行激烈體能運(yùn)動計(jì)劃時(shí)，必須有先行運(yùn)動壓力測試或其他適當(dāng)非侵襲性測試。而一般無癥狀病人以中度體能活動，一般不須先行運(yùn)動壓力測試。其他建議JNC6建議抽煙必須戒掉；酒須適量。這些建議也應(yīng)適用於糖尿病患。高血壓病患非藥物治療之實(shí)證(二)體能活動53StudyAgentPatientsAgeFollow-upChangeinBPInitialBPABCDEnalaprilNisodipine23523557.757.75NA156/98155/98FACETFosinoprilAmlodipine18919162.863.83.513/819/8170/95171/94HOTFelodipine150161.53.829.9/24.3170/105CAPPPCaptoprilB-blocker/Diuretic30926355.055.76.116/1016/10163.6/97.1163.3/97.3SHEPChlorthalidonePlacebo28330070.270.559.8/2.2170.2/72.9170.2/74.8Syst-EurNitredipinePlacebo252240≧60≧6028.6/3.8175.3/84.5BrilliantLisinoprilNifedipine167168≦75≦75116/1111/9163/99161/97MICRO-HOPERamiprilplacebo18081769≧554.52.4/1.0141.7142.3UKPDSCaptoprilAtenololPlacebo40035839056.356.056.58.49/410/5159/94159/93160/94糖尿病之高血壓之大型治療研究StudyAgentPatientsAgeFollow-up54SHEP研究中283位併單獨(dú)收縮高血壓之糖尿病患以Diuretic治療之效果風(fēng)險(xiǎn)減少(%)CurbJDetal.JAMA.1996;276:1886-1892.0-10-20-30-40-50-60T-JWU主要CV事件腦卒中心肌梗塞全數(shù)死亡率SHEP研究中283位併單獨(dú)收縮高血壓之糖尿病患以Diure55UKPDSBPControlStudy:

TightvsLessTightControlChangesinSBPandDBP801001201401600123456789Bloodpressure(mmHg)YearsfromrandomizationSystolicbloodpressureDiastolicbloodpressureLesstightTightLesstightTightLesstightcontrolStart160/94mmHgFinish154/87mmHgTightcontrolStart161/94mmHgFinish144/82mmHg

UKPDSGroup.BMJ.1998;317:703-713.T-JWUUKPDSBPControlStudy:

Tight560.2

Anydiabetes-relatedendpoint 50.9 67.4

Deathsrelatedtodiabetes 13.7 20.3

All-causemortality 22.4 27.2

Myocardialinfarction 18.6 23.5

Stroke 6.5 11.6

Peripheralvasculardisease 1.4 2.7

Microvasculardisease 12.0 19.2

UKPDSBPControlStudy:

AbsoluteandRelativeRiskDecreased

riskIncreased

riskLesstightcontrolTightcontrolUKPDSGroup.BMJ.1998;317:703-713.Favors

tightcontrolFavorsless

tightcontrolAbsoluterisk

(eventsper1000patient-years)Relativerisk*(95%CI)*Vslesstightcontrol.150.2 UKPDSBPControlStudy:

57Bloodpressure(mmHg)UKPDSBPControlStudy:

ACEInhibitorvsβ-blocker

608010014016018002468Cohort,MeanValuesYearsfromrandomizationSystolicbloodpressureDiastolicbloodpressureTherewerenodifferencesinBP-loweringefficacybetweenanACEinhibitor(captopril)anda-blocker(atenolol).Lesstightcontrol

ACEinhibitor

-blockerUKPDSGroup.BMJ.1998;317:713-720.T-JWUBloodpressure(mmHg)UKPDSBP58

AnACEinhibitor(captopril)andaα-blocker(atenolol)reducedtheriskofdiabeticcomplicationstoasimilarextent*95%CIforallvalues,except99%CIforretinopathyand

albuminuria;?2-stepchange.1.101.271.140.430.280.44Anydiabetes-relatedendpointDiabetes-relateddeathsAll-causemortalityRR

P

value1.201.121.290.350.740.30MyocardialinfarctionStrokeMicrovasculardiseaseRetinopathyprogressionat7.5y? 0.91 0.28Urinealbumin>50mg/Lat9y 1.21 0.31Urinealbumin>300mg/Lat9y 0.48 0.09Relative

risk*(95%CI)Favors

ACEinhibitorFavors

-blocker0.512UKPDSGroup.BMJ.1998;317:713-720.UKPDSBPControlStudy:

ACEInhibitorvsβ-BlockerT-JWUAnACEinhibitor(captopril)59以血管張力素轉(zhuǎn)化酵素抑制劑治療高血壓之糖尿病患的效果風(fēng)險(xiǎn)減少(%)HOPEstudyinvestigators.Lancet.2000;355:253-259.0-10-20-30-40心肌梗塞腦卒中CV死亡率明顯腎病變T-JWU以血管張力素轉(zhuǎn)化酵素抑制劑治療高血壓之糖尿病患的效果風(fēng)險(xiǎn)減少60EffectsofACEIonBPinHypertensiveType2DiabeticswithIncipientNephropathy

BRILLIANTAgardhC-D,etal.JHumHypertens1996;10:185-192LisinoprilNifedipine18016014012010080SittungBP(mmHg)MonthofTreatment0136912EffectsofACEIonBPinHyper61EffectsofACEIonUrinaryAlbuminExcretioninHypertensiveType2DiabeticswithIncipientNephropathyAgardhC-D,etal.JHumHypertens1996;10:185-192LisinoprilNifedipine[p<0.0006vs.placeboat12months]T-JWUAlbuminExcretion(μg/min)Baseline6month12month70605040302010BRILLIANTEffectsofACEIonUrinaryAlb62ACEIImprovesAlbuminExcretionRateinMicroalbuminuricPatientswithT1DM：

EUrodiabControlledtrialofLisinoprilinInsulin

dependentDiabetes(EUCLID)

EUCLIDStudyGroup.Lancet1997;349:1787-1792AER(μg/min)Time(months)706050403020106121824PlaceboLisinoprilTreatmentdifference=38.5μg/min,p=0.001T-JWUACEIImprovesAlbuminExcretio63MalaiseandfatigueEdemaGItractDiseases

RenalFailure

Cough

ErectiledysfunctionHeadacheDepressionRashAllergicreaction

Intermittentclaudication

BronchospasmColdandnumbhandHypokalemiaHyponatremia)

SideEffectACEICCBDiureticsβ-blockersNo.(%)(n=635)(n=235)(n=283)(n=358)高血壓糖尿病患降血壓治療之主要不良反應(yīng)DataSources:ACEI:ABCD,UKPDS;CCB:ABCD;Diuretics:SHEP;β-blockers:UKPDSTJWU21(3.3)11(1.7)9(1.4)6(0.9)29(4.6)3(0.5)2(0.3)1(0.2)1(0.2)7(1.1)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)20(8.5)4(1.7)2(0.9)8(3.4)2(0.9)10(4.3)0(0.0)1(0.4)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)13(4.6)0(0.0)34(11.9)0(0.0)11(3.9)0(0.0)0(0.0)0(0.0)0(0.0)70(24.8)6(2.3)22(7.9)16(4.5)0(0.0)5(1.4)0(0.0)0(0.0)

6(1.7)3(0.8)1(0.3)0(0.0)2(0.6)15(4.2)22(6.2)0(0.0)0(0.0)0(0.0)MalaiseandfatigueSideEffect64DiureticBeta-blockersACEinhibitorCCBAlpha-blockers血糖↑↑中性中性中性血脂肪↑↑中性中性中性電解質(zhì)干擾中性中性中性中性胰島素抗性↑↑↓中性↓併發(fā)癥冠心病保護(hù)(A)保護(hù)(A)保護(hù)(A)未評未定腎病變未評保護(hù)(A)保護(hù)(A)保護(hù)*(C)未評腦卒中保護(hù)(A)保護(hù)(A)保護(hù)(A)保護(hù)*(A)未評降血壓藥物對高血壓糖尿病患之影響DiureticBeta-blockersACEinhib65NephroprotectiveRoleofAngiotensinIIReceptorAntagon