19/4/2015

Potassiumandhypertension

OfficialreprintfromUpToDate
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Potassiumandhypertension
Authors
NormanMKaplan,MD
DavidBMount,MD

SectionEditor
GeorgeLBakris,MD

DeputyEditor
JohnPForman,MD,MSc

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Nov26,2013.
INTRODUCTIONAlowdietaryintakeofpotassiummayincreasethebloodpressure,andpotassium
supplementationalmostalwayslowerselevatedbloodpressure.Thedatademonstratingtheseassociations,
aswellasthepotentialmechanisms,willbereviewedhere.Theapproachtopatientswhopresentwith
concurrenthypertensionandhypokalemia,andtheclinicalfeaturesofprimaryaldosteronismarediscussed
separately.(See"Approachtothepatientwithhypertensionandhypokalemia"and"Pathophysiologyand
clinicalfeaturesofprimaryaldosteronism".)
POTASSIUMINTAKEANDBLOODPRESSUREThelevelofpotassiumintakecanaffectblood
pressure.Theeffectvarieswiththedirection(lowpotassiumintakeraisesthebloodpressureandhigh
potassiumintakelowersthebloodpressure)andmagnitudeofchangeinpotassiumintake.
LowpotassiumdietLowdietarypotassiumintake(below40meq/day[1.5g/day])hasbeenassociated
withanelevationinbloodpressureandanincreasedriskofstroke[1,2].Thefollowingobservationsillustrate
therangeoffindings:
Intwodifferentstudies,oneinhealthynormotensivemen[3]andoneinpatientswithprimary
hypertension(formerlycalledessentialhypertension)[4],potassiumrestrictionfromanormalintakeof80
to90meq/daydownto10to18meq/dayledtoastatisticallysignificant4to5mmHgincreaseinsystolic
bloodpressure.Theincreaseinbloodpressuremayhavebeenmediatedinpartbysodiumretention.
Inaprospectivecohortstudy,individualswithalowdietarypotassiumintake(lessthan64meq/day[2.4
g/day])hada50percentincreaseintheriskofstroke,independentofotherriskfactorssuchasthe
systemicbloodpressureanddiuretictherapy[2].
Similarfindingswerenotedinaretrospectiveanalysisof28,880patientsatincreasedcardiovascularrisk
intworandomizedtrials[1].Atamedianfollowupof56months,theriskofstrokewashighestin
patientswith24hoururinepotassiumexcretionlessthan40meq/day(6.2percent)andfellprogressively
athigherratesof24hoururinepotassiumexcretiontoalowof3.5percentatmorethan80meq/day.
Inadditiontotheadverseeffectsoflowdietarypotassiumintake,theratioofdietarysodiumtopotassium
intakecanalsoinfluencebloodpressure.InareportfromtheDallasHeartStudy,eachthreeunitincreasein
theurinesodiumtopotassiumratio,whichcanreflectincreasedsodiumintakeand/orreducedpotassium
intake,wasassociatedwitha1.6/1mmHgelevationinbloodpressure[5].
HighpotassiumdietIncontrasttotheriseinbloodpressureassociatedwithalowpotassiumdiet,
potassiumsupplementationlowersthebloodpressuresignificantlyinhypertensivepatientsandinsignificantly
innormotensivepatients.Themagnitudeofchangewasillustratedinasystematicreviewthatincludedmeta
analysesofbothrandomizedtrialsandcohortstudies[6].Thefollowingfindingswerenoted:
Inthemetaanalysisof16randomizedtrialsinhypertensivepatients,increasedpotassiumintake
significantlyreducedsystolicbloodpressurebyameanof5.3/3.1mmHg.Incontrast,thereductionin
systolicbloodpressurewassmall(0.1/0.6mmHg)andnotstatisticallysignificantinthreetrialsin
normotensivesubjects.
Whenasubgroupanalysiswasperformedaccordingtoachievedpotassiumintake,patientswithan
increaseto90to120meq/dayhadthelargestreductioninbloodpressure(7.2/4.1mmHg).
Inanothermetaanalysis,theeffectofpotassiumsupplementationonbloodpressurewasgreaterinblacks
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thaninwhites[7].Urinarypotassiumexcretioninblacksisconsistentlylessthaninwhites[8,9].This
differenceisdueinparttolessdietarypotassiumintakeinblacks[9,10].
Inadditiontothelowerrateofpotassiumintake,anotherfactorthatmaycontributetotheincreased
predispositiontohypertensioninblacksisarelativeincreaseintheactivityoftheNaK2Clcotransporterinthe
luminalmembraneinthethickascendinglimboftheloopofHenleandthemaculadensa(figure1)[8].This
defectcouldcontributetothedecreasedplasmareninactivity,lowerrateofurinarypotassiumexcretion,and
increasedsaltsensitivityoftenseeninblacks.
ClinicalimplicationsBasedupontheaboveobservations,ithasbeenproposedthathypertensivepatients
withnormalornearnormalrenalfunctionshouldbeencouragedtomaintainahighpotassiumintakefromfresh
fruitsandvegetables[11].Dietarycounselingistheusualapproachtoincreasingpotassiumintake.
Potassiumchloridesupplementscanalsobeused,particularlyiftheserumpotassiumconcentrationislow.
However,ifthereisnoapparentcauseforthehypokalemia(eg,diuretictherapy,gastrointestinallosses),the
patientshouldbeevaluatedforthedisordersthatareassociatedwithbothhypertensionandhypokalemia.
Theseincludeprimaryaldosteronism,renovasculardisease,andCushing'ssyndrome.(See"Approachtothe
patientwithhypertensionandhypokalemia"and"Causesofhypokalemiainadults",sectionon'Diuretics'.)
FewAmericansachievetherecommendedlevelofpotassiumintake.InareportfromtheNationalHealthand
NutritionExaminationSurvey(NHANES)III,theaveragedailypotassiumintakeinadultswas74to82meq
(2.9to3.2g)inmenand54to59meq(2.1to2.3g)inwomen[12].Only10percentofmenandlessthan1
percentofwomenhadadailypotassiumintakeof120meq(4.7g)ormore.
Wedonotrecommendpotassiumsupplementationorahighpotassiumdiettoattainthesegoalsinpatientsat
riskforhyperkalemiadue,forexample,totherapywithangiotensininhibitors,potassiumsparingdiuretics,or
underlyingchronickidneydisease.
MECHANISMSThemechanismsbywhichpotassiumintakemightberelatedtohypertensionandvascular
diseasearenotwelldefined.Thereductioninbloodpressurewithpotassiumsupplementsmayberelatedto
decreasedvascularresponsivenesstovasopressors,particularlynorepinephrine[13].Inaddition,sodiumand
chlorideintakemaybeimportant.
RelationtosodiumexcretionTherelationshipbetweenpotassiumandbloodpressureappearstobeduein
parttochangesinsodiumexcretion,asnotedabove[5].Sodiumexcretionisdiminishedbyhypokalemiaora
lowpotassiumdietandincreasedwithpotassiumsupplements,apparentlythroughchangesinsodium
reabsorptionintheproximaltubuleand/orloopofHenle[14].(See'Potassiumintakeandbloodpressure'above
and"Hypokalemiainducedrenaldysfunction",sectionon'Increasedsodiumreabsorption'.)
RoleofchlorideintakeChlorideisanimportantdeterminantoftheriseinbloodpressureinsaltsensitive
formsofhypertension.Incomparison,dietarypotassium(eg,fromfruitsandvegetables)isprimarilyassociated
withorganicanionssuchascitrate,notchloride.(See"Saltintake,saltrestriction,andprimary(essential)
hypertension".)
Therelativeefficacyofpotassiumbicarbonateorpotassiumcitrate(citrateismetabolizedtobicarbonate)
supplementsandpotassiumchloridesupplementshasbeendirectlyevaluatedinrandomizedcrossovertrialsof
patientswithhypertension[15,16].Thebicarbonate,citrate,andchloridepreparationallproducedasimilar
reductioninbloodpressure.Thus,theavailableevidencedoesnotsupporttheaccompanyinganionbeing
importantintheeffectofpotassiumonbloodpressure.
SUMMARY
Maintenanceofadequatepotassiumintakeortheadministrationofpotassiumsupplementsusually
lowersthebloodpressure,particularlyinblacksandinpatientswhoarenotsodiumrestricted.
Furthermore,ahigherpotassiumintakereducestheriskofstroke.(See'Potassiumintakeandblood
pressure'aboveand'Relationtosodiumexcretion'above.)
Themechanismbywhichpotassiumreducesbloodpressureisnotclear.(See'Mechanisms'above.)
Someexpertssuggestthathypertensivepatientsshouldconsumeatleast120meq(4.7g)ofdietary
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potassium/dayprovidedtheydonothaveapredispositiontohyperkalemia.Thislevelofpotassiumintake
canbeachievedpreferablywithdietarycounseling.(See'Clinicalimplications'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. O'DonnellMJ,YusufS,MenteA,etal.Urinarysodiumandpotassiumexcretionandriskof
cardiovascularevents.JAMA2011306:2229.
2. GreenDM,RopperAH,KronmalRA,etal.Serumpotassiumlevelanddietarypotassiumintakeasrisk
factorsforstroke.Neurology200259:314.
3. KrishnaGG,MillerE,KapoorS.Increasedbloodpressureduringpotassiumdepletioninnormotensive
men.NEnglJMed1989320:1177.
4. CoruzziP,BrambillaL,BrambillaV,etal.Potassiumdepletionandsaltsensitivityinessential
hypertension.JClinEndocrinolMetab200186:2857.
5. HedayatiSS,MinhajuddinAT,IjazA,etal.Associationofurinarysodium/potassiumratiowithblood
pressure:sexandracialdifferences.ClinJAmSocNephrol20127:315.
6. AburtoNJ,HansonS,GutierrezH,etal.Effectofincreasedpotassiumintakeoncardiovascularrisk
factorsanddisease:systematicreviewandmetaanalyses.BMJ2013346:f1378.
7. WheltonPK,HeJ,CutlerJA,etal.Effectsoforalpotassiumonbloodpressure.Metaanalysisof
randomizedcontrolledclinicaltrials.JAMA1997277:1624.
8. AvivA,HollenbergNK,WederA.Urinarypotassiumexcretionandsodiumsensitivityinblacks.
Hypertension200443:707.
9. TurbanS,MillerER3rd,AngeB,AppelLJ.Racialdifferencesinurinarypotassiumexcretion.JAmSoc
Nephrol200819:1396.
10. FrisanchoAR,LeonardWR,BollettinoLA.Bloodpressureinblacksandwhitesanditsrelationshipto
dietarysodiumandpotassiumintake.JChronicDis198437:515.
11. AdroguHJ,MadiasNE.Sodiumandpotassiuminthepathogenesisofhypertension.NEnglJMed
2007356:1966.
12. AppelLJ,GilesTD,BlackHR,etal.ASHpositionpaper:dietaryapproachestolowerbloodpressure.J
AmSocHypertens20104:79.
13. BianchettiMG,WeidmannP,BerettaPiccoliC,FerrierC.Potassiumandnorepinephrineorangiotensin
mediatedpressorcontrolinprehypertension.KidneyInt198731:956.
14. GallenIW,RosaRM,EsparazDY,etal.Onthemechanismoftheeffectsofpotassiumrestrictionon
bloodpressureandrenalsodiumretention.AmJKidneyDis199831:19.
15. HeFJ,MarkanduND,ColtartR,etal.Effectofshorttermsupplementationofpotassiumchlorideand
potassiumcitrateonbloodpressureinhypertensives.Hypertension200545:571.
16. HeFJ,MarciniakM,CarneyC,etal.Effectsofpotassiumchlorideandpotassiumbicarbonateon
endothelialfunction,cardiovascularriskfactors,andboneturnoverinmildhypertensives.Hypertension
201055:681.
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GRAPHICS
IontransportinloopofHenle

Schematicrepresentationofthetransportmechanismsinthethick
ascendinglimboftheloopofHenle.TheNaKATPasepumpinthe
basolateral(peritubular)membranepumpssodium(Na)outof,and
potassium(K)into,thecell.ThiscreatesalowintracellularNa
concentrationwhichdrivesmanyofthecell'sreabsorptiveprocesses.
Theentryoffilteredsodiumchloride(NaCl)intothecellsismediated
byanelectroneutralNaK2Cl(NKCC2)cotransporterintheapical
(luminal)membrane.Thisisalsocalledthefurosemidesensitive
cotransporter.Theenergyforthisprocessisprovidedbythefavorable
inwardelectrochemicalgradientforNa(theintracellularNa
concentrationisverylowandthecellinterioriselectronegative).The
inwardmovementofKandCloccursagainsttheirelectrochemical
gradientsandispoweredbytheinwardmovementofNaintothecell.
ThereabsorbedNawhichhasenteredthecellispumpedoutbythe
NaKATPasepump.TheconcentrationofKinthefiltrateandtubular
fluidismuchlowerthanthatofNaandCl,andmuchofthe
reabsorbedKrecyclebackintothelumenthroughKchannels(ROMK)
intheapicalmembranetoallowcontinuedNaClreabsorption.This
movementofcationicKintothelumenplusthefluxofreabsorbedCl
outofthecellintotheperitubularcapillary(viaClchannels)causes
thelumentobecomemorepositivelychargedcomparedwiththecell
andperitubularspace.Thislumenelectropositivitycreatesan
electricalgradientthatpromotesthepassivereabsorptionofcations
Na,calcium(Ca),andmagnesium(Mg)viatheparacellularpathway
betweenthecells.ThemostimportantClchannelsinthesecellsare
ClCKb.AlsopresentbutnotascriticalaretheClCKachannels.Each
oftheseClchannelsrequiresinteractionwithasmallproteincalled
barttintofunctionnormally.ThesingleClchannelshowninthefigure
representsbothintactClCKaandClCKbchannels.
Graphic75301Version9.0

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Disclosures

Disclosures:NormanMKaplan,MDNothingtodisclose.DavidBMount,MDConsultant/AdvisoryBoards:ZSPharma[Potassiumbinders(Z
hyperkalemia].Consultant/AdvisoryBoards:MedtronicRelypsaBayerNovartisDSIBoehringerIngelheimLexiconJanssenAstraZeneca
Nothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultile
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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