HypertensionHypertensionisoneoftheprimereasonswhichcausethehighratesofdeathofangiocardiopathy

approximately

50%ofcerebralapoplexyandAMIwererelatedtohypertension.almost3millionpeoplediefromCardia-cerebrovascularDiseaseeveryyear，almost￥366billion-medicalexpenseswerepaidon

hypertension

Systemichypertension

?long-lasting,usuallypermanentincreaseofsystolicanddiastolicbloodpressure

primary(essential)hypertension–unknowncause;usuallycoincidenceofmorefactors–neural,hormonal,kidneydysfunction,...

secondary(symptomatic)hypertension–symptom(sign)ofotherdisease

Isolatedsystolichypertension

increasedsystolicbloodpressureatnormalordecreaseddiastolicBPpseudohypertension←rigidarteriesinoldage“whitecoathypertension“

–inducedbystressatphysicalexamination?maskedhypertension“-falsefindingofnormalbloodpressureduringtheexamination;oppositeofwhitecoathypertensionSecondaryhypertensionessentialhypertension–90to95%ofhighbloodpressureprevalence:

?children...about4%,mostlysecondary

?middleage...11-21%?50-59years

old...approximately44%?60-69years

old...approximately54%?morethan70yearsold...≥64%

(Standardguidelines,2ndedition)

ClassificationofhypertensionJointNationalCommitteeonPrevention,Detection,Evaluation,andTreatmentofHighBloodPressure

JNC8CategorySystolic(mmHg)Diastolic(mmHg)Normal<120and<80Pre-HTN120-139or80-89HypertensionStageI140-159or90-99StageII>160or>100ClassificationofBP–JNC8IdentifiableCausesofHTNSleepapneaDrug-inducedorrelatedcausesChronickidneydiseasePrimaryaldosteronismRenovasculardiseaseChronicsteroidtherapyandCushing’ssyndromePheochromocytomaCoarctationoftheaortaThyroidorparathyroiddiseaseObstructivesleepapneasyndrome：（OSAS）Approximately

50%withhypertensionFeature：snoremechanism：

recurrent

nocturnalhypoxemia

ObesityWeight：OverweightorobesityaresignificanceriskfactorofhypertensionBMI：kg/m2；Normal20-24；Overweight：≥25Obesity:30，35，40CardiovascularRiskfactorsHypertensionCigarettesmokingObesity(bodymassindex≥30kg/m2)PhysicalinactivityDyslipidemiaDiabetesmellitusMicroalbuminuriaorestimatedGFR<60mL/minAge(olderthan55formen,65forwomen)Familyhistoryofprematurecardiovasculardisease(menunderage55orwomenunderage65)RiskofcardiovasculardiseasesrelationshipbetweenBPandCVD(cardiovasculardisease)riskiscontinual,consistentandnotdependentonotherriskfactorsthehigherBP,thehigherriskofheartfailure,stroke,renaldiseases

eachincreaseofsystolicBPby20and

diastolicBPby

10mmHgdoublestheriskofCVD

NosogenesisofHypertensionDifferentindividualhasdifferentnosogenesisDifferentmechanisminvolveindifferentstagesmechanismofBPphysiologicalaccommodationis

independent

ofwhichinhypertensionItishardtoconfirmprimarymechanismofhypertension1.hyperfunctionofsympatheticnervoussystem:

Variouscauses→hyperactivityofsympatheticnervoussystem→increaseofconcentrationofcatecholamine→

increasedcontractilityofresistancearterioleDrug:β-Block2.Renalwater-sodiumretention:Inceasedbloodvolume→inordertoavoidexcessivetissueperfusion，increasedcontractilityofresistancearteriole→increasedperipheralvascularresistanceDrug:Diuretic3.Renin-angiotensin-aldosteroneSystemDrug：ARBandACEIReninARBsiteofactionAngiotensinIIreceptorsAngiotensinIIAngiotensinIAngiotensinogenACELowBloodPressure(liver)(kidney)Vasoconstriction+PVRAldosteroneNaretentionACEinhibitorsiteofaction

BloodPressurebradykinin4.Abnormaliontransportoncellmembrane

ActivitydecreasesofNa﹢—K﹢—ATPpumpandNa﹢—Ca﹢—ATPpump→IncreasedconcentrationofNa+andCa+incell→enhancevascularconstriction

Drug:CCB5InsulinResistance（IR）Pathologicalmechanism

Pathologicalmechanism1.hypertension2.arteriolelesion3.luminalstenosis

4.ischemia5.ischemicdamagesintargetorganEffectsOnCVSVentricularhypertrophy,dysfunctionandfailure.ArrhithymiasCoronaryarterydisease,AcuteMIArterialaneurysm,dissection,andrupture.Long-termHBP→arteriolelesion：smoothmusclecellinthemiddlelamellaofarteriole

proliferationandfibrosis

Long-termHBP→promoteformationanddevelopmentofatherosclorosisindistributingarteriesandlargeartery

Heart：HBP→leftventricularhypertrophy、hypertensive

heart

disease→Heartfailure

atherosclerosisplaquedisruptionTheEyesRetinopathy,retinalhemorrhagesandimpairedvision.Vitreoushemorrhage,retinaldetachmentNeuropathyofthenervesleadingtoextraoccularmuscleparalysisanddysfunctionNormal

RetinaHypertensive

RetinopathyA

BCA:HemorrhagesB:Exudates(FattyDeposits)C:CottonWoolSpots(MicroStrokes)EffectsonTheKidneysGlomerularsclerosisleadingtoimpairedkidneyfunctionandfinallyendstagekidneydisease.IschemickidneydiseaseespeciallywhenrenalarterystenosisisthecauseofHTNPathologicalmechanismKidneys：PressureintheBowman‘scapsule

↑、glomerularfibrosis

、atrophy

，atlastkidney

failure

Malignanthypertension：afferentvesselandinterlobularrenalartery→proliferativeintimitisandfibrinoidnecrosis→rapiddeteriorationinkidneyfunctionClinicalManifestationandComplicationSymptoms

ofHighBloodPressureOneofthemostdangerousaspectsof

hypertension

isthatyoumaynotknowthatyouhaveit.Theonlywaytoknowifyour

bloodpressure

ishighisthroughregularcheckups.Ifyourbloodpressureisextremelyhigh,theremaybecertainsymptomstolookoutfor,

including:Severe

headacheFatigue

orconfusionVision

problemsChestpainDifficultybreathingIrregularheartbeatBloodintheurinePoundinginyourchest,neck,orearsSignsAorticsecondsoundhyperfunctionSystolicmurmurAcceleratedhypertension

Inacceleratedhypertension,the"bottom"numberofabloodpressurereading(diastolicnumber)canriseto130mmHGorhigher.Othersymptomscanincludeblurredvision,decreasedurination,nausea,vomiting,andnumbnessoftheextremitiesandotherareasofthebody.Leftuntreated,itmaycausedeathComplicationsofProlongedUncontrolledHTNChangesinthevesselwallleadingtovesseltraumaandarteriosclerosisthroughoutthevasculatureComplicationsariseduetothe“targetorgan”dysfunctionandultimatelyfailure.Damagetothebloodvesselscanbeseenonfundoscopy.DissectionofaortaDiagnosisanddifferentialdiagnosis

Asystolicbloodpressure(SBP)

>139mmHgand/orAdiastolic(DBP)

>89mmHg.Basedontheaverageoftwoormoreproperlymeasured,seatedBPreadings.Oneachoftwoormoreofficevisits.AccurateBloodPressureMeasurement

Theequipmentshouldberegularlyinspectedandvalidated.Theoperatorshouldbetrainedandregularlyretrained.Thepatientmustbeproperlypreparedandpositionedandseatedquietlyforatleast5minutesinachair.Theauscultatorymethodshouldbeused.Caffeine,exercise,andsmokingshouldbeavoidedforatleast30minutesbeforeBPmeasurement.AnappropriatelysizedcuffshouldbeusedBPMeasurementAtleasttwomeasurementsshouldbemadeandtheaveragerecorded.CliniciansshouldprovidetopatientstheirspecificBPnumbersandtheBPgoaloftheirtreatment.DifferentialdiagnosisPrimaryhypertensionorsecondaryhypertensionIaboratoryinspection:blood、piss、ECG，ultrasoniccardiogram、ABPM，ntima-mediathickness

，Ankle/armbloodpressureratio

ect.HypertensionriskstratificationRiskfactorsAndhistoryHTNgrade1HTNgrade2HTNgrade3Nonelowmorderatehigh1~2morderatemorderateVeryhigh≥3，orwithdiabetes，orwithorgandamagehighhighVeryhighWithcomplicationVeryhighVeryhighVeryhighRiskstratificationandTargetorgandamageBenefitofBPreductionIn

clinicalstudieswasduringantihypertensivetherapyrecorded:35-40%incidencereductionofstroke20-25%incidencereductionofmyocardialinfarctionmorethan50%shareatincidencereductionofheartfailureitisassumedthatamongpatientsatfirststageofhypertension(140-159/90-99mmHg)and

withothercardiovascularriskfactors,permanentreductionofBPby

12mmHgduring10yearspreventsonedeathfrom11treatedpatients(whenCVSdiseaseororganaffection,itisonefrom9)

TreatmentThefinalgoalofantihypertensivetherapyisreductionofmortalityandmorbiditytoCVSand

renaldiseases.PrimarygoalisreductionofsystolicBP.WewanttoreachBPlessthan140/90mmHg(Torr),orlessthan130/80mmHgamongdiabeticpatientsandpatientswithkidneydiseasesNeededisalsoincreaseddetection!NonpharmacologicaltreatmentChangeoflife-style:

?intakeofsalt...≤5–6gperday?preventionofobesity–dieteticmodification

?alcohol...≤30gperday?smoking–stop?physicalactivity?psychicalrelaxation

Pharmacologictreatment

Antihypertensives

1stchoicedrugs:1.diuretics2.β-blockers3.inhibitorsofACE4.blockersofAT1receptors(ARB)5.calciumchannelblockers

2ndchoicedrugs–mainlytodrugcombinations:

α1-sympatholytics;α2-sympathomimetics;direct

vasodilators;kalliumchannelopeners;agonistsofI1receptorsinCNS;othermechanismsofaction

DiureticsDiuretics

1.carboanhydraseinhibitors(acetazolamid)–notusedinthetreatmentofhypertension

2.loopdiuretics(furosemide,etacrynicacid,bumetanide)–strongshort-lastingeffect;abilitytoexcreteto25%ofNa+fromfiltrate

?blockactivereabsorptionofNa+,Cl-,K+

fromascendinglimbofHenle′sloop?attreatmentofhypertensionisrarelyusedonlyfurosemide

inlowdosage–ifsimultaneouslyisverymuchreducedGfiltration;

theyaren′tsuitableforlong-lastingapplication

3.thiazidediuretics(hydrochlorothiazide,chlorthalidone,

clopamide)?blockreabsorptionofNa+andCl-fromdistaltubulus?effectisweakerasatloopdiuretics–theyexcreteabout

5%fromNa+filtrate?mostsuitablediureticsforlong–lastingtreatmentofhypertension

?effectalsoinvesselwall(↓volumeofNaand↓

reactivitytonorepinephrine;regressionofmedia

hypertrophy) →thiseffectischaracteristicforindapamidandmetipamid(increaseofdiuresisisnegligible)→alsocalled?diureticswithoutdiureticeffect“?themostisusedhydrochlorothiazide–dailydose12,5–25mg

MechanismofActionofThiazideDiuretics

4.

K-sparingdiuretics(spironolactone(aldosteroneantagonist),amiloride,triamterene)

?athypertensiononlyassistantdrugstocombinations

–tocorrecthypokalemia5.otherdiuretics?osmotic(mannitol,sorbitol)?xanthinediureticsaresuitablemainlyforolderpatientsandatsimultaneouschronicheartfailureADRs

ofthiazidediuretics-hypokalemia,hypovolemia,hyperuricemia,metabolicADRs(impairedglucosetoleranceanddyslipidemia-mostlyafterhighdoses),erectiledysfunction

β-blockersClassifications:1.non-selective(β1-ajβ2-effect–propranolol,metipranolol,...);

selective(β1-effect–metoprolol,bisoprolol,atenolol,...);

hybridsubstances(besideβ-effecthavealsoothereffects,additional,resp.β2-mimeticeffect),throughwhichtheyinducevazodilation–labetalol,carvedilol,nebivolol,...) –themostimportantclassification2.β-blockerswithISA(intrinsicsympathomimeticactivity–pindolol,acebutolol,...;≈parcialagonists)andwithoutISA3.hydrophilic(atenolol,celiprolol,...)andlipophilic

β-blockers(propranolol,metoprolol,carvedilol,...)4.classificationaccordingtogenerations.......andotherdifferentclassifications....β-blockers?preferencedareselectiveandhybridsubstancesbeforenonselective

?don′tdifferverymuchinantihypertensiveeffect,selectionaccordingtoadverseeffectprofile

?suitableforyoungerpatientswith↑sympathicoadrenalactivity,hyperkineticcirculation,patientsunderpsychicalstress;patients

withexistentischaemicheartdiseaseandmainlyaftermyocardialinfarction

?therearemainlyprescribed:

metoprolol(Vasocardin,Egilok,Betaloc)bisoprolol(Coronal,Bisogamma,Concor)

carvedilol(Dilatrend,Coryol,Talliton)nebivolol(Nebilet)and

accordingtotraditionnonselectivemetipranolol(Trimepranol)

MainEffectsofβ1-aβ2-blockade

?β-blockers–possibilitiesofcombinations:diuretics,Ca2+blockers–onlydihydropyridines!,α1-

sympatholytics,ACEI,vazodilatorsADRs:

?tendencytobronchoconstrictionandtovasoconstrictionintheperiphery–mainlyatnon-selectiveβB?metabolicADR–worseningoflipidogram;masksymptomsofhypoglycemiaandcanimpairglucosetollerance–moreatnon-selectiveβB?sleepdisturbances,baddreams→...depression?atveryhighdosescanworsenheartfailure;ifindicatedatchronicheartfailure,doseshouldbeincreasedstepbystep?erectiledysfunctionCalciumChannelBlockers(CCB)Classification:CCB–MechanismofActionBlockinfluxofcalciumtocellthroughslowL-typechannels,loweritsintracellularconcentrationwhatcausesrelaxationofsmoothmuscleinvesselwall,decreaseofcontractility,decreaseofelectricalirritabilityandconductivityCa2+ChannelBlockers(CCB)Differentchemicalstructures,withdifferenthaemodynamicandcliniceffectsAccordingtochemicalstructuredividedto: -dihydropyridins(amlodipine,felodipine,lacidipine,nifedipinewithslowrelease,isradipine) -phenylalkylamins(verapamil) -benzothiazepins(diltiazem)SelectivityofCCBBloodvesselsvasodilationofarterialvasculatureHeart:decreaseofHeartrateAVconductionStrenghtofcontractionCalciumchannelblockers

?attreatmentofhypertensionaremostlyused

dihydropyridines;verapamilonlyatpresenttachycardia

?prototypeshort-actingDHPnifedipineiscontraindicated!-itreducesBPtoorapidly,soinducesreflexactivationofsympaticuswithsubsequentincreaseofBPandsucharepeatedBPfluctuationcausesworsevesseldamageasuntreatedhypertension→insteadofmortalitydecreaseitsincrease!?pharmacokineticexplanation:effectfluctuatesforfluctuationoflevelinblood–haslowT/P(troughtopeakratio)?forantihypertensivetoreducemortalityandmorbidity,ithastoreduceBPslowlyandsuccessively,withoutreflexactivationofsympathicus→moresteadylevelandhigher

T/P

→FDAapprovesasantihypertensivesonlydrugs,thathave

T/Pmorethan50%?thisappliesforthe2ndgenerationofdihydropyridines(isradipine,felodipine,nitrendipine)and3rdgenerationofdihydropyridines(amlodipine,

lacidipine,lercanidipine).?Ca2+blockersaresuitabletotreathypertonicpatientswithDM,metabolicsyndrome,atischaemicdiseaseoflower

extremities?particularlyadvantageousareforisolatedsystolichypertension?possibilitiesofcombinations:ACEI,βB(onlydihydropyridines),diureticsADRs:headache,redface,perimalleolaredemas,constipation,tachycardia(dihydrop.),severebradycardia(non-dihydropyridins),stealphenomen?

nimodipine(1stgeneration)affinitytobrainvasculature→...effectivelyrelievesspasmsofcerebralarteries→usedatsubarachnoidbleeding

lercanidipinehashighT/Pratio

inourcountryforthetreatmentofhypertensionareprescribedmainlyfollowingdihydropyridines:

2ndgeneration:felodipine(Presid,Plendil),isradipine(Lomir),nitrendipine(Nitresan,Lusopress)

3rdgeneration:amlodipine(Amlopin,Agen,Tenox,Norvasc),lacidipine(Lacipil),lercanidipine(Lercal)

PharmacologicInterferencetoATCascadeInhibitorsofACenzyme

?blockthechangeof

angiotensinI

to

angiotensinIIandatthesametimeblockinactivationof

bradykinin?vazodilationinbothresistantand

capacitance

vessels?accentedindication:-hypertonicpeoplewithheartfailure(vasodilatingtherapyofcardialinsuficiency),alsoaftermyocardialinfarction

-hypertonicpeoplewithDManddifferentformsofdiabetic

nephropathystartingwithmikroalbuminuria(nephroprotectiveeffectofACEI)?excessiveinitialfallinBP→posturalhypotensionorsyncope;treatmentshouldbestartedinbedfromthelowestdoses?reactionof

airways

isoftenstrongandirritatingcough→intolleranceofthewholegroup→replacementtoAT1receptorblockers

?theyareadministeredas“prodrug“,toeffectivesubstancearechangedinliver

?effecttoreduceBPisinthewholegroupsimilar;theydifferonlyinpharmacokineticdependentfromstructure→divisionto

hydrophilic(“blood“)and

lipophilic(“tissue“)ACEI?hydrophilicactonlyinsidevesselsandinendothelium;lipophilicalsoontheoutersideofvessels(on

“adventicial“angiotenzinconvertase)and

inmyocardialinterstitium→probablymoreeffectivelyatregressionofleftventriculehypertrophyand

vesselmedia

?

typicalhydrophilicACEI:captopril(prototypesubstance–hasSH-group;nowadays usedonlyinhypertensioncrisis,Tensiomin)enalapril(Enap,Ednyt),lisinopril(Dapril,Diroton)

?typicallipophilicACEI:perindopril(Vidotin,Stopress,Prestarium)trandolapril(Actapril,Gopten)quinapril(Quinpres,Accupro)

?ADRs:impairedrenalfunction,hyperkalemia,hypotension,drycough,angioneuroticedema?contraindications:pregnancy!,highconcentrationofpotassiumandcreatinine,stenosisofa.renalisonbothsides,severeaortalstenosis,angioneuroticedemainanamnesis

MainBenefitsofACEinhibitionAT1receptorblockers

?themostoftenreplacementofACEIincaseofcough

?losartan(prototype;Cozaar),valsartan,kandesartan,irbesartan(Aprovel)

?sometimesprescribedas1stchoice,evenbeforeACEI←clinicalstudiesindicatethattheyhaveamongpatientswithHTandDM2slightlybetterprotectiveeffectsthanACEI

SelectionofpharmacotherapyResultsgainedinclinicalstudiesshowthatBPreductionwithusingfollowingantihypertensives–inhibitorsofangiotensinconvertingenzyme(ACEI),blockersofangiotensinreceptors(ARB),betablockers(βB),calciumchannelblockers(Ca2+B)a

diuretics,canreducecomplicationsofhypertension.BaseofmedicamenttreatmentofuncomplicatedhypertensioninthefirststageshouldbeaccordingtoJNC7thiazidediureticsalone,orincombinationwithotherantihypertensivesinthesecondstageofhypertension.

Hypertensive

emergency

Principleoftreatment：Theadministrationofan

nitroprusside

injectionissuitable.Theinitialgoalinhypertensiveemergenciesistoreducethepressurebynomorethan25%(withinminutesto1or2hours),andthentowardalevelof160/100

mmHgwithinatotalof2–6hours.Itisalsoimportantthatthebloodpressurebeloweredsmoothly,nottooabruptly.3.oralagentscanbeused,butallhaveadelayedonsetofaction.Severalprincipleofmanagement1.Cerebral

hemorrhage:Antihypertensivetherapywouldnotbecarriedoutinacutestage,onlyBP>200/130mmHg,therapycouldbetakenintoaccount.(TargetBP:<160/100mmHg)2.Cerebralinfarction:Antihypertensivetherapywouldnotbecarriedout.

3.Acutecoronarysyndrome:NitroglycerinordiltiazemIvgtt，β-blockersandACEIp.o.(target:withnopain,DBP<100mmHg)4.Acuteleftventricularfailure:Sodiumnitroprussideornitroglycerin、loopdiuretic.SecondaryhypertensionHTNaffects43millionadultsinUS95%have“essentialHTN”withoutidentifiableandtreatablecause“Secondary”HTNaccountsfor~5-10%ofothercasesandrepresentspotentiallycurablediseaseOftenoverlookedandunderscreenedControversyoverscreeningandtreatmentinsomecasesScreeningTestingcanbeexpensiveandrequiresclinicalsuspicionandknowledgeoflimitationsofdifferenttestsGeneralprinciples:NewonsetHTNif<30or>50yearsofageHTNrefractorytomedicalRx(>3-4meds)Specificclinical/labfeaturestypicalfordzi.e.,hypokalemia,epigastricbruits,differentialBPinarms,episodicHTN/flushing/palp,etcCausesofSecondaryHTNCommonIntrinsicRenalDiseaseRenovascularDzMineralocorticoidexcess/aldosteronism?SleepBreathingd/oUncommonPheochromocytomaGlucocorticoidexcess/Cushing’sdzCoarctationofAortaHyper/hypothyroidismRenalParenchymalDiseaseCommoncauseofsecondaryHTN(2-5%)HTNisbothcauseandconsequenceofrenaldiseaseMultifactorialcauseforHTNincludingdisturbancesinNa/waterbalance,depletionorantagonismofvasodepressors/prostaglandins,pressoreffectsonTPRRenaldiseasefrommultipleetiol,treatunderlyingdisease,dialysis/transplantifnecessaryRenovascularHTNIncidence1-30%EtiologyAtherosclerosis75-90%Fibromusculardysplasia10-25%OtherAortic/renaldissectionTakayasu’sarteritisThrombotic/cholesterolemboliCVDPosttransplantationstenosisPostradiationRenovascularHTN-PathophysiologyDecreaseinrenalperfusionpressureactivatesRAAS,reninreleaseconvertsangiotensinogenAngI;ACEconvertsAngIAngIIAngIIcausesvasoconstriction(amongothereffects)whichcausesHTNandenhancesadrenalreleaseofaldosterone;leadstosodiumandfluidretentionContralateralkidney(ifunilateralRAS)respondswithdiuresis/Na,H2OexcretionwhichcanreturnplasmavolumetonormalwithsustainedHTN,plasmareninactivitydecreases(limitedusefulnessfordxBilateralRASorsolitarykidneyRASleadstorapidvolumeexpansionandultimatedeclineinreninsecretionRenovascularHTN-ClinicalHistoryonsetHTNage<30or>55SuddenonsetuncontrolledHTNinpreviouslywellcontrolledptAccelerated/malignantHTNIntermittentpulmedemawithnlLVfxnPE/LabEpigastricbruit,particularysystolic/diastolicAzotemiainducedbyACEIUnilateralsmallkidneyRenovascularHTN-diagnosisPhysicalfindings(bruit)DuplexU/SCaptoprilrenographyMagneticResonanceAngiographyRenalAngiographyAtheroscleroticRAS75-90%ofRASUsuallymen,age>55,otheratheroscleroticdzProgressionofstenosis51%@5years,3-16%toocclusion,withrenalatrophynotedin21%ofRASlesions>60%ESRDin11%(higherriskif>60%,baselinerenalinsufficiency,SBP>160)TreatmentPTRAsuccess60-80%withrestenosis10-47%Stentsuccess94-100%withrestenosis11-23%(1yr)“Cure”ofRVHTN<30%FibromuscularDysplasia,beforeandafterPTRAAtheroscleroticRASbeforeandafterstentRenovascularHTN–MedicalRxAggressiveriskfxmodification(lipid,tobacco,etc)ACEI/ARBsafeinunilateralRASifcarefultitrationandclosemonitoring;contraindicatedinbilatRASorsolitarykidneyRASPr