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OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate

Cardiovascularrisksofhypertension
Author
NormanMKaplan,MD

SectionEditors
GeorgeLBakris,MD
BernardJGersh,MB,ChB,DPhil,
FRCP,MACC

DeputyEditor
JohnPForman,MD,MSc

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2015.|Thistopiclastupdated:Jun04,2014.
INTRODUCTIONHypertensionisquantitativelythemostimportantriskfactorforprematurecardiovascular
disease,beingmorecommonthancigarettesmoking,dyslipidemia,anddiabetes,whicharetheothermajorrisk
factors(table1).Hypertensionaccountsforanestimated54percentofallstrokesand47percentofallischemic
heartdiseaseeventsglobally[1].(See"Overviewoftheriskequivalentsandestablishedriskfactorsfor
cardiovasculardisease".)
Hypertensionincreasestheriskforavarietyofcardiovasculardiseases[2],includingstroke,coronaryartery
disease,heartfailure,atrialfibrillation[3],andperipheralvasculardisease.Coronarydiseaseinmenandstrokein
womenaretheprincipalfirstcardiovasculareventsnotedafterhypertensiononset,asobservedfromdatafromthe
FraminghamHeartStudy[4].Inviewoftheevidencethatthemortalityratesarerisinginyoungerpeopleinthe
UnitedStates[5]andtheincreasingimpactofcardiovasculardiseasesindevelopingcountries[6],greater
attentionmustbegiventopreventionofthesediseases.(See"Definitionandpathogenesisofleftventricular
hypertrophyinhypertension"and"Overviewoftheriskequivalentsandestablishedriskfactorsforcardiovascular
disease".)
Theriskforbothcoronarydiseaseandstrokeincreasesprogressivelywithincrementalincreasesinbloodpressure
above115/75mmHg,asshowninnumerousepidemiologicstudies(figure1AB)[710].However,these
observationsdonotproveacausalrelationshipsinceincreasingbloodpressurecouldbeamarkerforotherrisk
factorssuchasincreasingbodyweight,whichisassociatedwithdyslipidemia,glucoseintolerance,andthe
metabolicsyndrome.Thebestevidenceforacausalroleofincreasingbloodpressureincardiovascular
complicationsisanimprovementinoutcomewithantihypertensivetherapy[11].(See"Hypertension:Whoshould
betreated?"and"Themetabolicsyndrome(insulinresistancesyndromeorsyndromeX)".)
Theincreaseincardiovascularriskhasprimarilybeendescribedintermsofelevatedsystolicpressureinthose
overage60years[12]andelevationindiastolicpressureinyoungerindividuals.Pulsepressure,whichisthe
differencebetweenthesystolicanddiastolicbloodpressuresandisdeterminedprimarilybylargearterystiffness,
isalsoastrongpredictorofrisk[12].(See"Hypertension:Whoshouldbetreated?",sectionon'WhatlevelofBP
increasesrisk?'.)
Projectionshavebeenmadefortheexpecteddecreaseinmorbidityandmortalityresultingfroma10to12mmHg
reductioninsystolicpressureanda5to6mmHgreductionindiastolicpressureusingdatafrommultipleclinical
trialsperformedoverthepast30years.Althoughnotprovingcauseandeffect,theestimatedbenefitfromthis
degreeofbloodpressureloweringisa38percentreductioninriskofstrokeanda16percentreductioninriskof
coronarydisease[13].
ADDITIVEEFFECTSOFMULTIPLERISKFACTORSAsmostvividlyportrayedintheFraminghamHeart
Study,whichhasbeenongoingfordecades,thedifferentcoronaryriskfactorshaveanadditiveeffectonthe
likelihoodofdevelopingcoronaryheartdisease[14,15].Inadditiontohypertension,themajorriskfactorsareolder
age,elevatedplasmacholesterol,alowHDLcholesterol,diabetesmellitus,cigarettesmoking,andleftventricular
hypertrophy(LVH)byelectrocardiogram.Thus,individualpatientswhohavesignificanthypertensionbutnoneor
fewoftheotherriskfactorsareatrelativelylessoverallriskthanarepatientswithlesshypertensionbutmoreof
theotherriskfactors(figure2)[14,16].Specificissuesrelatedtocardiovascularriskfactorsinwomenare
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discussedseparately.(See"Determinantsandmanagementofcardiovascularriskinwomen".)
TheFraminghamfindingshavebeenreplicated[1719],butthedegreeofcardiovascularriskrelatedtothe
Framinghamriskcriteriamaynotapplytoallpatientpopulations[2022].Asanexample,aprospectivecohort
studyofover4000middleagedEuropeanpatientswithhypertensionevaluatedtheactualriskofcoronaryheart
diseaseandstrokeatamedianfollowupof3.7yearsversusthepredictedriskinthistimeperiodasprovidedby
theFraminghamdata[20].TheactualriskofcoronarydiseasewasoverestimatedbytheUnitedStatesdatainall
countries,rangingfrom2percentintheUnitedKingdomto7percentinFrance,whilethepredictedandactual
risksforstrokeweresimilar.
OtherriskfactorshavebeenproposedtoimproveupontheFraminghamriskassessment,includingCreactive
protein,brainnatriureticpeptide,echocardiographyandotherstudiesfordetectingsubclinicalvasculardisease[23
25].However,nonehasbeenproventoaddsignificantlytotheFraminghamscoring,andtheyareprobablynot
costeffective.
APPLICATIONOFRISKASSESSMENTTOTHERAPEUTICDECISIONSAgroupfromNewZealandhas
takentheseriskfactorsintoaccountindeterminingtheoverallriskstatusofindividualpatients,alongwiththeir
levelofbloodpressure,age,andgender[16].Theythenexaminedtheevidenceofbenefitsofantihypertensive
therapyfromtheclinicaltrialsandconsideredthecostsofsuchtherapy,concludingthatantihypertensivetherapy
canbejustifiedonlyiftheriskforamajorcardiovasculareventoverthenextfiveyearswas10percentorgreater,
orifthelevelofbloodpressurewassohighastomandatetherapyregardlessofoverallriskstatus(170/100
mmHg).
Thisapproachrequiresthatage,gender,andanumberofcardiovascularriskfactorsbetakenintoaccountwhen
consideringwhenhypertensionshouldbetreated(figure2)[16].
CurrentriskversuspriorriskInadditiontothespecificpatientpopulation[20],anotherproblemwiththeuse
ofsuchdataisthattheriskstatusthatiscurrentlyassessedmaynotreflectwhatwaspresentpreviously.Thisis
animportantissuebecauseitisthepriorriskstatusthatismorelikelytoberesponsibleforthecurrenthealthof
theindividual.
Asanexample,althoughbloodpressureatthetimeofriskassessment(currentbloodpressure)istypicallyused
inmostpredictionalgorithms,thisdoesnotaccuratelyreflectanindividual'spastbloodpressureexperiencethe
useoflongtermaveragebloodpressureismoreaccurate.Thisissupportedbythefollowingobservations:
Inastudyof3560individuals,thepresenceofprehypertensionbeforeage35yearswasassociatedwith
coronarycalcification(whichisastrongpredictoroffuturecoronaryheartdisease)laterinlife.This
associationwasobservedafteradjustingforbloodpressureandothercoronaryriskfactorsthatwerepresent
afterage35years[26].
AreportfromtheFraminghamHeartStudyfoundthatrecentandremoteantecedentbloodpressure(systolic,
diastolic,andpulsepressure)predictedcardiovascularriskincrementallyovercurrentbloodpressure[27].
Thiseffectwasseeninmenandwomen,youngerandoldersubjects,andlowerandhigherbloodpressure
groups.
Inanotherstudy,1604menwhoseriskstatuswasfirstassessedwhentheywereaged45to64yearsand
freeofclinicallyobviouscardiovasculardiseasewerethenreassessed25yearslaterwhentheywereaged
70to90years[28].Mostpatientschangedtheirriskstatusoverthistimeperiod,movingforwardor
backward.Whenthecurrentriskstatusofthe342subjectswhodevelopedcardiovasculardisease
(myocardialinfarction,angina,coronarybypasssurgery,angioplasty,orstroke)duringthefollowupperiod
wascomparedwiththatofthe279whoremainedhealthy,therewerefewdifferences.However,theresults
weredifferentwhentheoriginalriskstatuswasused.Thosepatientswhoremainedhealthyhadsignificantly
lowerbloodpressure(121/79versus134/83mmHg)andplasmacholesterollevels(211versus226mg/dL
[5.45versus5.84mmol/L])25yearsbefore.
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Theauthors'conclusionsinjectsomeneededcautionintheuseofriskfactoranalysiswhendecidingtotreat
hypertensioninoldersubjects:"Sincemidlifevaluesaremorelikelytorepresentlifelongexposurevaluesthat,in
turn,makethemaincontributiontothedevelopmentofatherosclerosis,investigatorsandcliniciansmayneedto
becautiousinusingriskfactorvaluesmeasuredlateinlifeastheonlymeansofassessingriskforsubsequent
disease"[28].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
BeyondtheBasicstopics(see"Patientinformation:Highbloodpressureinadults(BeyondtheBasics)"and
"Patientinformation:Highbloodpressuretreatmentinadults(BeyondtheBasics)")
SUMMARYOverallcardiovascularriskassessment,aswellasbloodpressure,shouldbetakenintoaccount
whendecidinguponpropertreatmentinapatientwithmildhypertension.Atleastsomeofthebloodpressure
measurementsshouldbeobtainedoutoftheofficetoavoidunnecessarytreatmentof"whitecoat"hypertension
andtofacilitaterecognitionof"maskedhypertension."(See"Ambulatorybloodpressuremonitoringandwhitecoat
hypertensioninadults".)
Lifestylemodifications(nonpharmacologictherapy)shouldberecommendedtoallpatientswithbloodpressures
between120to139/80to89mmHg(nowdefinedasprehypertension)andalsotoallthosewithsustained
hypertension.(See"Prehypertension".)
Antihypertensivedrugsshouldbeinstitutedif,afterseveralbloodpressuremeasurements,theaverageblood
pressureis140/90mmHg.Thegoalbloodpressureislessthan140/90mmHginmostpatients.Goalblood
pressureinpatientswithatheroscleroticcardiovasculardisease,diabetesmellitus,orchronickidneydiseaseis
discussedseparately.(See"Whatisgoalbloodpressureinthetreatmentofhypertension?"and"Bloodpressure
managementinpatientswithatheroscleroticcardiovasculardisease",sectionon'Goalbloodpressure'and
"Treatmentofhypertensioninpatientswithdiabetesmellitus",sectionon'Goalbloodpressure'and
"Antihypertensivetherapyandprogressionofnondiabeticchronickidneydiseaseinadults",sectionon'Blood
pressuregoal'.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. LawesCM,VanderHoornS,RodgersA,InternationalSocietyofHypertension.Globalburdenofblood
pressurerelateddisease,2001.Lancet2008371:1513.
2. RapsomanikiE,TimmisA,GeorgeJ,etal.Bloodpressureandincidenceoftwelvecardiovasculardiseases:
lifetimerisks,healthylifeyearslost,andagespecificassociationsin125millionpeople.Lancet2014
383:1899.
3. AngeliF,ReboldiG,VerdecchiaP.Hypertension,inflammationandatrialfibrillation.JHypertens2014
32:480.
4. LloydJonesDM,LeipEP,LarsonMG,etal.Novelapproachtoexaminingfirstcardiovasculareventsafter
hypertensiononset.Hypertension200545:39.
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5. GreenlandP,LloydJonesD.Timetoendthemixedandoftenincorrectmessagesaboutpreventionand
treatmentofatheroscleroticcardiovasculardisease.JAmCollCardiol200750:2133.
6. LimSS,GazianoTA,GakidouE,etal.Preventionofcardiovasculardiseaseinhighriskindividualsinlow
incomeandmiddleincomecountries:healtheffectsandcosts.Lancet2007370:2054.
7. LewingtonS,ClarkeR,QizilbashN,etal.Agespecificrelevanceofusualbloodpressuretovascular
mortality:ametaanalysisofindividualdataforonemillionadultsin61prospectivestudies.Lancet2002
360:1903.
8. PastorBarriusoR,BanegasJR,DaminJ,etal.Systolicbloodpressure,diastolicbloodpressure,and
pulsepressure:anevaluationoftheirjointeffectonmortality.AnnInternMed2003139:731.
9. PletcherMJ,BibbinsDomingoK,LewisCE,etal.Prehypertensionduringyoungadulthoodandcoronary
calciumlaterinlife.AnnInternMed2008149:91.
10. ShenL,MaH,XiangMX,WangJA.Metaanalysisofcohortstudiesofbaselineprehypertensionandriskof
coronaryheartdisease.AmJCardiol2013112:266.
11. BloodPressureLoweringTreatmentTrialists'Collaboration,NinomiyaT,PerkovicV,etal.Bloodpressure
loweringandmajorcardiovasculareventsinpeoplewithandwithoutchronickidneydisease:metaanalysis
ofrandomisedcontrolledtrials.BMJ2013347:f5680.
12. StaessenJA,GasowskiJ,WangJG,etal.Risksofuntreatedandtreatedisolatedsystolichypertensionin
theelderly:metaanalysisofoutcometrials.Lancet2000355:865.
13. BloodPressureLoweringTreatmentTrialists'Collaboration,TurnbullF,NealB,etal.Effectsofdifferent
regimenstolowerbloodpressureonmajorcardiovasculareventsinolderandyoungeradults:metaanalysis
ofrandomisedtrials.BMJ2008336:1121.
14. WilsonPW.Establishedriskfactorsandcoronaryarterydisease:theFraminghamStudy.AmJHypertens
19947:7S.
15. KannelWB,WolfPA.FraminghamStudyinsightsonthehazardsofelevatedbloodpressure.JAMA2008
300:2545.
16. JacksonR,LawesCM,BennettDA,etal.Treatmentwithdrugstolowerbloodpressureandblood
cholesterolbasedonanindividual'sabsolutecardiovascularrisk.Lancet2005365:434.
17. LloydJonesDM,EvansJC,LevyD.Hypertensioninadultsacrosstheagespectrum:currentoutcomesand
controlinthecommunity.JAMA2005294:466.
18. FrostPH,DavisBR,BurlandoAJ,etal.Coronaryheartdiseaseriskfactorsinmenandwomenaged60
yearsandolder:findingsfromtheSystolicHypertensionintheElderlyProgram.Circulation199694:26.
19. LoweLP,GreenlandP,RuthKJ,etal.Impactofmajorcardiovasculardiseaseriskfactors,particularlyin
combination,on22yearmortalityinwomenandmen.ArchInternMed1998158:2007.
20. BastujiGarinS,DeverlyA,MoyseD,etal.TheFraminghampredictionruleisnotvalidinaEuropean
populationoftreatedhypertensivepatients.JHypertens200220:1973.
21. ConroyRM,PyrlK,FitzgeraldAP,etal.Estimationoftenyearriskoffatalcardiovasculardiseasein
Europe:theSCOREproject.EurHeartJ200324:987.
22. ZambonA,ArfA,CorraoG,ZanchettiA.Relationshipsofdifferenttypesofeventtocardiovasculardeath
intrialsofantihypertensivetreatment:anaidtodefinitionoftotalcardiovasculardiseaseriskinhypertension.
JHypertens201432:495.
23. SimonA,ChironiG,LevensonJ.Performanceofsubclinicalarterialdiseasedetectionasascreeningtest
forcoronaryheartdisease.Hypertension200648:392.
24. OlsenMH,WachtellK,NielsenOW,etal.Nterminalbrainnatriureticpeptidepredictedcardiovascular
eventsstrongerthanhighsensitivityCreactiveproteininhypertension:aLIFEsubstudy.JHypertens2006
24:1531.
25. CuspidiC,MeaniS,ValerioC,etal.Leftventricularhypertrophyandcardiovascularriskstratification:
impactandcosteffectivenessofechocardiographyinrecentlydiagnosedessentialhypertensives.J
Hypertens200624:1671.
26. SipahiI,TuzcuEM,SchoenhagenP,etal.Effectsofnormal,prehypertensive,andhypertensiveblood
pressurelevelsonprogressionofcoronaryatherosclerosis.JAmCollCardiol200648:833.
27. VasanRS,MassaroJM,WilsonPW,etal.Antecedentbloodpressureandriskofcardiovasculardisease:
theFraminghamHeartStudy.Circulation2002105:48.
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28. BenfanteR,HwangLJ,MasakiK,CurbJD.Towhatextentdocardiovascularriskfactorvaluesmeasured
inelderlymenrepresenttheirmidlifevaluesmeasured25yearsearlier?Apreliminaryreportandcommentary
fromtheHonoluluHeartProgram.AmJEpidemiol1994140:206.
Topic3850Version13.0

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GRAPHICS
Componentsofcardiovascularriskfactorsinpatientswith
hypertension
Majorriskfactors

Targetorgandamage

Hypertension

Heartdisease

Cigarettesmoking

Leftventricularhypertrophy

Obesity(BMI30kg/m2)

Anginaorpriormyocardialinfarction

Physicalinactivity

Priorcoronaryrevascularization

Dyslipidemia
Diabetesmellitus
MicroalbuminuriaorestimatedGFR<60mL/min
Age>55yearsformen,>65yearsinwomen
Familyhistoryofprematurecoronarydisease

Heartfailure

Strokeortransientischemicattack
Chronickidneydisease
Peripheralarterialdisease
Retinopathy

Men<55years
Women<65years

DatafromTheSeventhReportoftheJointNationalCommitteeonPrevention,Detection,Evaluation,
andTreatmentofHighBloodpressure.TheJNC7report.JAMA2003289:2560.
Graphic81993Version1.0

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CHDmortalityrelatedtobloodpressureandage

Coronaryheartdisease(CHD)mortalityrate,picturedonalogscalewith95percent
confidenceintervals,ineachdecadeofageinrelationtotheestimatedusualsystolic
anddiastolicbloodpressureatthestartofthatdecade.CHDmortalityincreaseswith
bothhigherpressuresandolderages.Fordiastolicpressure,eachagespecific
regressionlineignoresthelefthandpoint(ie,atslightlylessthan75mmHg)forwhich
theriskliessignificantlyabovethefittedregressionline(asindicatedbythebrokenline
below75mmHg).
Datafrom:ProspectiveStudiesCollaboration,Lancet2002360:1903.
Graphic75106Version5.0

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Strokemortalityrelatedtobloodpressureandage

Strokemortalityrate,picturedonalogscalewith95percentconfidenceintervals,
ineachdecadeofageinrelationtotheestimatedusualsystolicanddiastolic
bloodpressureatthestartofthatdecade.Strokemortalityincreaseswithboth
higherpressuresandolderages.Fordiastolicpressure,eachagespecific
regressionlineignoresthelefthandpoint(ie,atslightlylessthan75mmHg),for
whichtheriskliessignificantlyabovethefittedregressionline(asindicatedby
thebrokenlinebelow75mmHg).
DatafromProspectiveStudiesCollaboration,Lancet2002360:1903.
Graphic66793Version2.0

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Additiveeffectsofriskfactorsoncardiovasculardiseaseatfive
years

CumulativeabsoluteriskofCVDatfiveyearsaccordingtosystolicbloodpressureand
specifiedlevelsofotherriskfactors.Thereferencecategoryisanondiabetic,
nonsmoking50yearoldwomanwithaserumTCof154mg/dL(4.0mmol/L)andHDL
cholesterolof62mg/dL(1.6mmol/L).TheCVDrisksaregivenforsystolicblood
pressurelevelsof110,130,150,and170mmHg.Intheothercategories,the
additionalriskfactorsareaddedconsecutively.Asanexample,thediabetescategory
isa50yearolddiabeticmanwhoisasmokerandhasaTCof270mg/dL(7mmol/L)
andHDLcholesterolof39mg/dL(1mmol/L).
CVD:cardiovasculardiseaseTC:totalcholesterol.
Adaptedfrom:JacksonR,LawesCM,BennettDA,etal.Lancet2005365:434.
Graphic55353Version7.0

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Disclosures
Disclosures:NormanMKaplan,MDNothingtodisclose.GeorgeLBakris,MDGrant/Research/ClinicalTrialSupport:Medtronic
Relypsa[Hypertension,hyperkalemia].Consultant/AdvisoryBoards:MedtronicRelypsaBayerNovartisDSIBoehringerIngelheim
LexiconJanssenAstraZenecaKona[Diabetes,hyperkalemia,resistanthypertension(Canagliflozin,dapagliflozin,empagliflozin)].
BernardJGersh,MB,ChB,DPhil,FRCP,MACCConsultant/AdvisoryBoards:Medtronic[Cardiovascular(MemberofRevealSteering
Committee)]BaxterHealthcareCorporation[Cardiovascular(ClinicaldevelopmentofautologousCD34+stemcells)]Cardiovascular
ResearchFoundation[Cardiovascular(SymplicityHTN3trialandMASTERIItrial)]St.JudeMedical[Cardiovascular(FAMEIITrial)]
OrthoMcNeillJanssenScientificAffairs[Cardiovascular(MemberofExecutiveCommittee)]TEVAPharmaceuticals[Cardiovascular
(ChairmanofDSMBonstemcelltrial)]BostonScientific[Cardiovascular(Transcutaneousaorticvalvereplacementtrial)].JohnP
Forman,MD,MScNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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