高血压(英文版)-课件

Hypertension

Hypertension

1IntroductionHypertensionisamajorpublichealthproblemthroughouttheworldbecauseofitshighprevalenceanditsassociationwithincreasedriskofcardiovasculardisease.Approximately100millionChinesehaveelevatedBP.Ofthese,77%areawareoftheirdiagnosis,70%arereceivingtreatment,andonly33%areundercontrol.IntroductionHypertensionisa2Definition

HypertensionisdefinedasaSBPof140mmHgorgreaterand/oraDBPof90mmHgorgreaterinsubjectswhoarenottakingantihypertensivemedication.Essentialorprimaryhypertensionisahypertensionofunknowncause.IsolatedsystolichypertensionisdefinedasSBPof140mmHgorgreateranddiastolicBPlessthan90mmHg.

DefinitionHypertensionisdef3ClassificationofBloodPressureLevels(mmHg)CategorySystolicDiastolicOptimal<120<80Normal<130<85High-normal130-13985-89Grade1hypertension(mild)140-15990-99Subgroup:borderline140-14990-94Grade2hypertension(moderate)160-179100-109Grade3hypertension(severe)≥180≥110

Isolatedsystolichypertension≥140<90Subgroup:borderline140-149<90

ClassificationofBloodPressu4Notes1.Whenapatient’sSBPandDBPfallintodifferentcategories,thehighercategoryshouldapply.e.g.154/100mmHgisdefinedasgrade2hypertension.180/82mmHgisdefinedasgrade3isolatedsystolichypertension.Notes1.Whenapatient’sSBPa5Notes(Continue)2.BPisbasedontheaverageoftwoormorereadingstakenateachoftwoormorevisitsafteraninitialscreening(筛查).e.g.12/2firstvisit:172/102mmHg,168/104mmHg.13/2secondvisit:158/98mmHg,158/96mmHg.TheaverageBPis164/100mmHg,whichisdefinedasgrade2hypertension.Notes(Continue)2.BPisbased6Notes(continue)3.Thepatientshouldbeclearlyinformedthatasingleelevatedreadingdoesnotconstituteadiagnosisofhypertensionbutisasignthatfurtherobservationisrequired.Forinstance:21/31stvisit:146/98mmHg,150/98mmHg23/32ndvisit:128/84,126/8027/33rdvisit:130/80,130/82Notes(continue)3.Thepatient7Notes(continue)4.OptimalBPwithrespecttocardiovascularriskislessthan120/80mmHg.However,unusuallylowreadingsshouldbeevaluatedforclinicalsignificance.Forexample,70/50mmHgislessthan120/80mmHg,butitisnotoptimal.Notes(continue)4.OptimalBPw8ClassificationofBloodPressureLevels(mmHg)CategorySystolicDiastolicHypotension???<90<60Optimal<120<80Normal<130<85High-normal130-13985-89Grade1hypertension(mild)140-15990-99Subgroup:borderline140-14990-94Grade2hypertension(moderate)160-179100-109Grade3hypertension(severe)≥180≥110

Isolatedsystolichypertension≥140<90Subgroup:borderline140-149<90

ClassificationofBloodPressu9EpidemiologyPrevalencerate（患病率）ofhypertensioninChina:In1959,5.11%In1979,7.73%In1991,11.88%TheprevalenceofhighBPincreaseswithage.Hypertensionismorecommoninmenthaninwomenuptoage50,afterthatage,hypertensionismorecommoninwomen.HypertensionismorecommoninnorthernChinathaninsouthernChina.

EpidemiologyPrevalencerate（患病10EtiologyandpathogenesisofEHNocausecanbeestablishedPossiblemechanismsGenetictendency

SpontaneoushypertensionratEHtendstoclusterinfamiliesHighsaltintakesomehypertensives

Vascularendotheliumdysfunction

nitricoxideendothelinEtiologyandpathogenesisofE11PathogenesisofEH(Continue)Insulinresistance(胰岛素抵抗)sodiumreabsorption,sympatheticnervoussystemactivity,intracellularNaCaCigarettesmokingbyincreasingplasmanorepinephrine(去甲肾上腺素)Excessiveuseofalcoholperhapsbyincreasingplasmacatecholamines儿茶酚胺So,thepathogenesisofEHismultifactorial.PathogenesisofEH(Continue)12ClinicalfindingsSymptoms:MildtomoderateEHisusuallyassociatedwithnormalhealthformanyyears.Somepatientshaveheadache,tinnitus（耳鸣）,palpitation,tiredness（疲劳）,andsoon.Signs:BPiselevated.Somepatientshavealoudaorticsecondsoundandanearlysystolicejectionclick(收缩期喷射喀喇音).

ClinicalfindingsSymptoms:13Clinicalfindings(Continue)Complications:HypertensivecardiovasculardiseaseHypertensivecerebrovasculardiseaseHypertensionisthemajorpredisposingcauseofstroke.

HypertensiverenaldiseaseChronichypertensionleadstonephrosclerosis(肾硬化症)Aorticdissection

Clinicalfindings(Continue)Com14LaboratoryinvestigationsRoutineinvestigationsHemoglobin,urinalysis&renalfunctionstudies,todetecthematuria,proteinuria,andcasts,Serumpotassium,sincehypokalemia

istypicalofhyperaldosteronism（醛固酮增多症）

Fastingglucose,sincehyperglycemiaisnotedindiabetesandpheochromocytoma（嗜铬细胞瘤）

Plasmacholesterol,asanindicatorofatherosclerosis

riskLaboratoryinvestigationsRouti15Laboratoryinvestigations(Continue)Serumuricacid(尿酸),sinceifelevateditisacontraindicationtodiuretictherapyElectrocardiography,

todetectventricularhypertrophyChestX-ray,todetectleftventricularenlargementFunduscopicexamination:retinaarteriolarnarrowingarteriovenousnicking(动静脉交叉压迫)hemorrhage,exudate(渗出)papilledema(视神经乳头水肿)

Laboratoryinvestigations(Cont16Laboratoryinvestigations(Continue)OptionalinvestigationsPlasmarenin(肾素)activity&aldosterone(醛固酮),urinaryVMA（香草杏仁酸），toidentify

secondaryhypertensionEchocardiography,todetectventricularhypertrophyVascularultrasonographyshouldbeperformedifarterialdiseaseissuspected.Renalultrasonographyshouldbeperformedifrenaldiseaseissuspected.

Laboratoryinvestigations(Cont17ClinicbloodpressuremeasurementWiththepatientssittingafter5ormoreminutesofrest.Twoorthreemeasurementsshouldbetakenateachvisit.ThesystolicreadingistakenasthelevelofBPatwhichclearsoundsareheardwitheachheartbeat.Thediastolicreadingistakenatthelevelwhensoundsdisappear.Clinicbloodpressuremeasurem18AmbulatoryBPmonitoring(动态血压监测)NoninvasiveautomaticdeviceisavailableforambulatoryBPmonitoringoverperiodsof24hormore.ABPMofferstheadvantagesofprovidingamorerealisticsettingforBPmeasurements.

TherearelimiteddataavailableabouttheprognosticvalueofABPM.ABPMisnotasubstituteforofficemeasurement.AmbulatoryBPmonitoring(动态血压监19NormalreferenceofABPM(mmHg）

24hDaytimeNighttimeSBPDBPSBPDBPSBPDBPStaessen1133821408812576JNC-VI21358512075China31308013585125751.JHyperten.1994;12:(Suppl7):S1;2.ArchInternMed.1997;157:2413;3.中华心血管杂志，1995；23：325。NormalreferenceofABPM(mmHg20SituationsinwhichABPMshouldbeconsideredUnusualvariabilityofbloodpressureoverthesameordifferentvisitsOfficeorwhitecoathypertension(白大衣性高血压)SymptomssuggestinghypotensiveepisodesHypertensionresistanttodrugtreatmentSituationsinwhichABPMshoul21Diagnosis&differentialdiagnosisToconfirmachronicelevationofbloodpressureanddetermineitslevelTodeterminethepresenceoftarget-organdamageandtoquantifyitsextentTosearchforothercardiovascularriskfactors&clinicalconditionsthatmayinfluenceprognosis&

treatmentToidentifysecondarycausesofhypertensionDiagnosis&differentialdiagn22Classificationofhypertension(mmHg)CategorySystolicDiastolicGrade1hypertension(mild)140-15990-99Subgroup:borderline140-14990-94Grade2hypertension(moderate)160-179100-109Grade3hypertension(severe)≥180≥110

Isolatedsystolichypertension≥140<90Subgroup:borderline140-149<90Thisclassificationisnotperfect.Thereasonisasfollows:

Classificationofhypertension23Classificationofhypertension(Continue)

Theprognosis(预后)ofpatientswithhypertensionshouldnotbebasedonthelevelofBPalone,butalsoonthepresenceofotherriskfactors,concomitantdiseasessuchasdiabetes,targetorgandamage&cardiovascularorrenaldisease.e.g.No1hypertensivepatient:142/96mmHgwithheartfailureNo2hypertensivepatient:164/100withoutheartfailureWhoseprognosisisbetter?So,weshouldfindawaytoavoidthedefect(缺陷)ofthisclassification.Classificationofhypertension24StratificationofRisktoQuantifyPrognosisBloodPressure（mmHg）OtherRiskFactorsGrade1Grade2Grade3&DiseaseHistorySBP140-159SBP160-179SBP≥180ororDBP90-99orDBP100-109DBP≥110InootherriskfactorsLowRiskMEDRisk

HighRiskII1-2riskfactors

MEDRisk

MEDRiskVery-High-RiskIII≥3riskfactorsorTODHighRiskHighRiskVery-High-RiskorDiabetesIVACCVery-High-RiskVery-High-RiskVery-High-RiskACC(associatedclinicalconditions)并存的临床情况StratificationofRisktoQuan25RiskfactorsusedforriskstratificationLevelsofSBPandDBP(grades1-3)Men>55yearsWomen>65yearsSmokingTC>5.72mmol/LDiabetesFamilyhistoryofprematurecardiovasculardisease（早发心血管病家族史）（Men<55years，Women<65years）Riskfactorsusedforriskstr26Target-organdamageLeftventricularhypertrophy（ECG、echocardiographyorchestX-ray）Proteinuria(蛋白尿)and/orslightelevationofplasmacreatinine（肌酐）concentration(106-177mol/L)Ultrasoundorradiologicalevidenceofatheroscleroticplaque(动脉粥样斑块)

(carotid、femoralarteries（股动脉）andaorta）Generalizedorfocalnarrowingoftheretinalarteries（视网膜动脉）Target-organdamageLeftventri27AssociatedclinicalconditionsCerebrovasculardisease

IschemicstrokeCerebralhemorrhageTransientischemicattackHeartdisease

MyocardialinfarctionAnginaCongestiveheartfailureRenaldiseaseDiabeticnephropathyRenalfailure（plasmaCr>177mol/L）VasculardiseaseDissectinganeurysmAdvancedhypertensiveretinopathyHemorrhageorexudatesPapilledemaAssociatedclinicalconditions28StratificationofRisktoQuantifyPrognosisBloodPressure（mmHg）OtherRiskFactorsGrade1Grade2Grade3&DiseaseHistorySBP140-159SBP160-179SBP≥180ororDBP90-99orDBP100-109DBP≥110InootherriskfactorsLowRiskMEDRisk

HighRiskII1-2riskfactors

MEDRisk

MEDRiskVery-High-RiskIII≥3riskfactorsorTODHighRiskHighRiskVery-High-RiskorDiabetesIVACCVery-High-RiskVery-High-RiskVery-High-RiskStratificationofRisktoQuan29Treatmentstrategies&riskstratificationLow-riskgroup:monitorBPandotherriskfactorsfor6months，ifgoalBPisnotattained,drugtreatmentshouldbeinitiated.Medium-riskgroup:begindrugtreatmentHigh-riskgroup&Very-high-riskgroup:shouldbegindrugtreatmentLifestylemodificationshouldbeusedinallhypertensivepatientsTreatmentstrategies&riskst30ExampleApatientwithdiabetes（糖尿病）&BPof140/94mmHgplusleftventricularhypertrophy

shouldbeclassifiedashavinggrade1hypertensionwithtargetorgandiseaseandwithanothermajorriskfactor.

wouldbecategorizedas“grade1hypertension,high-risk”

wouldberecommendedforimmediateinitiationofdrugtreatmentandalsolifestylemodificationExampleApatientwithdiabete31TreatmentThegoalofantihypertensivetherapyistoreducecardiovascularmorbidity(发病率)&mortality(死亡率).TheBPgoalofantihypertensivetherapy

ToachievehighnormalBP(below140/90mmHg)inelderlypatientsToachievenormalBP(below130/85mmHg)inyoung,middle-agedordiabeticsubjectsTreatmentThegoalofantihype32NonpharmacologicaltreatmentsShouldbeusedinallhypertensivepatients,eitherasdefinitivetreatmentorasanadjuncttodrugtherapy.

Shouldbetailoredtotheindividualcharacteristicsofeachpatient,suchasweightreductionforanoverweightpatient.Include:

Weightreduction

Complexdietarychanges

Increasedphysicalactivity

Smokingcessation

OthersNonpharmacologicaltreatments33Lifestylemodification(Continue)

WeightreductionThroughacombinationofdietarycaloricrestriction&increasedphysicalactivitySustainedweightreductionissodifficulttoachieve,so,moreemphasisshouldbeplacedonpreventionofweightgain.Patientsshouldavoidappetitesuppressantdrug（食欲抑制药）anddietpill(减肥药丸)Lifestylemodification(Contin34Lifestylemodification(Continue)ComplexdietarychangesReductioninsaltintake<6g/dofsodiumchloride(3*6*30=540)ReducingfatintakeIncreasingfruitandvegetableModerationofalcoholconsumptionforaheavydrinkerLifestylemodification(Contin35Lifestylemodification(Continue)Increasedphysicalactivity

RegularaerobicphysicalactivitycanlowerBPandisrecommendedforallhypertensiveindividuals.

PatientswithadvancedcardiovasculardiseasemayrequiremedicalevaluationbeforeinitiationofexerciseKeepingpsychologicequilibriumSmokingcessationLifestylemodification(Contin36PharmacologictherapyPrinciplesofdrugtreatmentTheuseoflowdosesofdrugstoinitiatetherapyTheuseoflong-actingdrugsproviding24hefficacyonaonce-dailybasisTheuseofappropriatedrugcombinationstomaximizehypotensiveefficacywhileminimizingsideeffectsPharmacologictherapyPrinciple37SixmaindrugclassesDiuretics(利尿剂):DHCT,Furosemide(呋塞米)β-blockers:Atenolol,MetoprololCCB:Nifedipine,Amlodipine

ACEinhibitors:Enalapril,CaptoprilAIIantagonists:Losartan,Valsartan-blockers:Prazosin,TerazosinSixmaindrugclassesDiuretics38GuidelinesforselectingdrugtreatmentofhypertensionClassofdrugIndications(适应证)PossibleindicationsContraindicationsDiureticsHeartfailureDiabetesGoutSystolichypertension

-BlockersAnginaMIAsthmaandCOPDTachyarrhythmiasPregnancyHeartblock

ACEIHeartfailurePregnancyDiabeticnephropathyHyperkalemiaAfterMIRenalarterystenosisCCBAnginaSystolichypertension-blockersProstatichypertrophyGlucoseintolerance（前列腺肥大）DyslipidemiaAⅡantagonistsACEIcoughsameasACEIGuidelinesforselectingdrug39Antihypertensivedrugtherapyforpatientswithco-morbidconditionsIndicationDrugtreatment

DiabeteswithproteinuriaACEinhibitorsHeartfailureACEinhibitors,diureticsIsolatedsystolichypertensionDiuretics,CablockersMyocardialinfarctionβ-blocker,ACEinhibitorsAnginaβ-blocker,CablockersBenignprostatichyperplasiaα-blocker

Dyslipidemiaα-blockerTachyarrhythmiasβ-blocker,CablockersAntihypertensivedrugtherapy40SecondaryhypertensionItisahypertensionofknowncause.

TheimportanceofidentifyingpatientswithSHisthattheycansometimesbecuredbysurgeryorbyspecificmedicaltreatment.Secondaryhypertensionincludes:

Renalparenchymaldiseases(肾实质病变)

Renovascularhypertension

Adrenaldiseases（肾上腺疾病）SecondaryhypertensionItisa41RenalparenchymaldiseasesThemostcommoncausesofSHAnydiseasesoftherenalparenchyma(肾实质):glomerulonephritis(肾小球肾炎),diabeticnephropathy(肾病),polycystickidneys(多囊肾).MostcasesarerelatedtoincreasedintravascularvolumeorincreasedactivityoftheRASRenalparenchymaldiseasesThe42RenovascularhypertensionDiagnosticclues:Theonsetisbelowage20orafterage50Upperabdominalbruit(杂音)

Abruptdeterioration（恶化）inrenalfunctionafteradministrationofACEIThehypertensionisdifficulttocontrol.Renalangiography（肾血管造影术）isthebestdiagnostictest.RenovascularhypertensionDiagn43Pheochromocytoma(嗜铬细胞瘤)Clinicalclues:Paroxysmal（阵发性）hypertensionEpisodesofdiaphoresis(出汗),palpitation,headache,pallor(苍白)Laboratoryinvestigations:Bloodcatecholamines（儿茶酚胺）areelevatedUrinaryvanillylmandelicacid（香草基杏任酸）CTorMRI(magneticresonanceimaging)Pheochromocytoma(嗜铬细胞瘤)Clinica44Primaryhyperaldosteronism

（原发性醛固酮增多症）Episodesofgeneralizedmuscularweaknessorparalysis(瘫痪)

aswellaspolyuriaandnocturia(夜尿)HypokalemiaAldosterone（醛固酮）concentrationsinurineandbloodareelevatedPatientswithasolitary(孤立的)

adenoma(腺瘤)

shouldundergoresectionofthetumorPatientswithbilateraladrenalhyperplasia(增生)aretreatedwithspironolactone(螺内酯)Primaryhyperaldosteronism

（原发45OthercausesofsecondaryhypertensionCushing’ssyndromeCoarctationoftheaorta(主动脉缩窄)Estrogen（雌激素）usePregnancy(妊娠)Othercausesofsecondaryhype46Homework1What’sthedefinitionofHypertension?2Howtoclassifythehypertension?3Whataretheindicationsandcontraindicationsofsixmainantihypertensivedrugs?4Illustrate4kindsofthecommonsecondaryhypertension.5Studythespecialclinicaltypesofhypertensionbyyourself(includingmalignanthypertension(恶性高血压),hypertensivecrisis(危象),hypertensiveencephalopathy(高血压脑病)&elderlyhypertensive)Homework1What’sthedefinitio47Thankyouverymuch

foryourattention!Thankyouverymuch

foryoura48Hypertension

Hypertension

49IntroductionHypertensionisamajorpublichealthproblemthroughouttheworldbecauseofitshighprevalenceanditsassociationwithincreasedriskofcardiovasculardisease.Approximately100millionChinesehaveelevatedBP.Ofthese,77%areawareoftheirdiagnosis,70%arereceivingtreatment,andonly33%areundercontrol.IntroductionHypertensionisa50Definition

HypertensionisdefinedasaSBPof140mmHgorgreaterand/oraDBPof90mmHgorgreaterinsubjectswhoarenottakingantihypertensivemedication.Essentialorprimaryhypertensionisahypertensionofunknowncause.IsolatedsystolichypertensionisdefinedasSBPof140mmHgorgreateranddiastolicBPlessthan90mmHg.

DefinitionHypertensionisdef51ClassificationofBloodPressureLevels(mmHg)CategorySystolicDiastolicOptimal<120<80Normal<130<85High-normal130-13985-89Grade1hypertension(mild)140-15990-99Subgroup:borderline140-14990-94Grade2hypertension(moderate)160-179100-109Grade3hypertension(severe)≥180≥110

Isolatedsystolichypertension≥140<90Subgroup:borderline140-149<90

ClassificationofBloodPressu52Notes1.Whenapatient’sSBPandDBPfallintodifferentcategories,thehighercategoryshouldapply.e.g.154/100mmHgisdefinedasgrade2hypertension.180/82mmHgisdefinedasgrade3isolatedsystolichypertension.Notes1.Whenapatient’sSBPa53Notes(Continue)2.BPisbasedontheaverageoftwoormorereadingstakenateachoftwoormorevisitsafteraninitialscreening(筛查).e.g.12/2firstvisit:172/102mmHg,168/104mmHg.13/2secondvisit:158/98mmHg,158/96mmHg.TheaverageBPis164/100mmHg,whichisdefinedasgrade2hypertension.Notes(Continue)2.BPisbased54Notes(continue)3.Thepatientshouldbeclearlyinformedthatasingleelevatedreadingdoesnotconstituteadiagnosisofhypertensionbutisasignthatfurtherobservationisrequired.Forinstance:21/31stvisit:146/98mmHg,150/98mmHg23/32ndvisit:128/84,126/8027/33rdvisit:130/80,130/82Notes(continue)3.Thepatient55Notes(continue)4.OptimalBPwithrespecttocardiovascularriskislessthan120/80mmHg.However,unusuallylowreadingsshouldbeevaluatedforclinicalsignificance.Forexample,70/50mmHgislessthan120/80mmHg,butitisnotoptimal.Notes(continue)4.OptimalBPw56ClassificationofBloodPressureLevels(mmHg)CategorySystolicDiastolicHypotension???<90<60Optimal<120<80Normal<130<85High-normal130-13985-89Grade1hypertension(mild)140-15990-99Subgroup:borderline140-14990-94Grade2hypertension(moderate)160-179100-109Grade3hypertension(severe)≥180≥110

Isolatedsystolichypertension≥140<90Subgroup:borderline140-149<90

ClassificationofBloodPressu57EpidemiologyPrevalencerate（患病率）ofhypertensioninChina:In1959,5.11%In1979,7.73%In1991,11.88%TheprevalenceofhighBPincreaseswithage.Hypertensionismorecommoninmenthaninwomenuptoage50,afterthatage,hypertensionismorecommoninwomen.HypertensionismorecommoninnorthernChinathaninsouthernChina.

EpidemiologyPrevalencerate（患病58EtiologyandpathogenesisofEHNocausecanbeestablishedPossiblemechanismsGenetictendency

SpontaneoushypertensionratEHtendstoclusterinfamiliesHighsaltintakesomehypertensives

Vascularendotheliumdysfunction

nitricoxideendothelinEtiologyandpathogenesisofE59PathogenesisofEH(Continue)Insulinresistance(胰岛素抵抗)sodiumreabsorption,sympatheticnervoussystemactivity,intracellularNaCaCigarettesmokingbyincreasingplasmanorepinephrine(去甲肾上腺素)Excessiveuseofalcoholperhapsbyincreasingplasmacatecholamines儿茶酚胺So,thepathogenesisofEHismultifactorial.PathogenesisofEH(Continue)60ClinicalfindingsSymptoms:MildtomoderateEHisusuallyassociatedwithnormalhealthformanyyears.Somepatientshaveheadache,tinnitus（耳鸣）,palpitation,tiredness（疲劳）,andsoon.Signs:BPiselevated.Somepatientshavealoudaorticsecondsoundandanearlysystolicejectionclick(收缩期喷射喀喇音).

ClinicalfindingsSymptoms:61Clinicalfindings(Continue)Complications:HypertensivecardiovasculardiseaseHypertensivecerebrovasculardiseaseHypertensionisthemajorpredisposingcauseofstroke.

HypertensiverenaldiseaseChronichypertensionleadstonephrosclerosis(肾硬化症)Aorticdissection

Clinicalfindings(Continue)Com62LaboratoryinvestigationsRoutineinvestigationsHemoglobin,urinalysis&renalfunctionstudies,todetecthematuria,proteinuria,andcasts,Serumpotassium,sincehypokalemia

istypicalofhyperaldosteronism（醛固酮增多症）

Fastingglucose,sincehyperglycemiaisnotedindiabetesandpheochromocytoma（嗜铬细胞瘤）

Plasmacholesterol,asanindicatorofatherosclerosis

riskLaboratoryinvestigationsRouti63Laboratoryinvestigations(Continue)Serumuricacid(尿酸),sinceifelevateditisacontraindicationtodiuretictherapyElectrocardiography,

todetectventricularhypertrophyChestX-ray,todetectleftventricularenlargementFunduscopicexamination:retinaarteriolarnarrowingarteriovenousnicking(动静脉交叉压迫)hemorrhage,exudate(渗出)papilledema(视神经乳头水肿)

Laboratoryinvestigations(Cont64Laboratoryinvestigations(Continue)OptionalinvestigationsPlasmarenin(肾素)activity&aldosterone(醛固酮),urinaryVMA（香草杏仁酸），toidentify

secondaryhypertensionEchocardiography,todetectventricularhypertrophyVascularultrasonographyshouldbeperformedifarterialdiseaseissuspected.Renalultrasonographyshouldbeperformedifrenaldise