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www.medscape.com

StudyReopensRiftOverMeritsofLowSodium-for-AllPublic-HealthPolicies

May27,2016
HAMILTON,ONApooledanalysisinvolvingmorethan130,000peoplefrom49
countriesaddstoagrowingbodyofevidencethatlowsodiumintakemaybeharmful,
butacceptanceisfarfromuniversal[1].

Comparedwithaveragesodiumintake(3to6g/day),lowsodiumintake(<3g/day)
wasassociatedwithanincreasedriskofcardiovasculareventsanddeathregardlessof
whetherthepatienthadhypertensionornot.
Incontrast,highsodiumintake(>6g/day)wasassociatedwithincreasedriskonlyin
hypertensivepatients,accordingtotheinvestigators,ledbyDrAndrewMente
(McMasterUniversity,Hamilton,ON).

"Themessageisthatpopulationwidesodiumreductionisprobablyill-advised,andwe
needtosimplyidentifytheindividualswhohavebothhypertensionandconsumehigh
amountsofsodiumandgetthemtoreducetheirsodiumintaketomoderatelevels.
Thatwouldbetheidealapproach,"Mentetoldheartwire fromMedscape,notingthat
onlyabout10%ofthepopulationhadhypertensionandhighsodiumintake.
Reversing Progress

ThestudypromptedaswiftresponsewhenpublishedonlineMay20,2016inthe
Lancet.Inastatement,AmericanHeartAssociation(AHA)presidentDrMarkCreager
(Dartmouth-HitchcockMedicalCenter,Lebanon,NH)expressedconcernthatadopting
theauthors'recommendation"mayreversetheprogressthathasoccurredinmodifying
dietarysodiumintakeandreducingtheriskofhighbloodpressureanditseffecton
heartdiseaseandstroke."
ImmediateAHApast-presidentDrElliottAntman(Brigham&Women'sHospital,
Boston,MA)saidthestudyshouldbe"disregarded"andcriticizeditsuseofasingle
urinetesttoassesssodiumintake."Thisisaflawedstudy,andyoushouldn'tuseitto
informyourselfabouthowyou'regoingtoeat.TheAHAhasreviewedthetotalityofthe
evidenceandwecontinuetomaintainthatnomorethan1500mgofsodiumadayis
bestforidealhearthealth."
Anticipatingthiscriticism,theauthorspointedoutthatuseofoneovernighturine
samplehasbeenvalidatedagainstthegoldstandardof24-hoururinecollectionsin
priorstudiesinhealthyindividualsandhypertensivesaswellasintheirown
internationalvalidationstudy.Theanalysesalsoadjustedforday-to-dayvariability.

Althoughtheinvestigatorsusedgroup-levelmeasuresofintakeinestimatingsodium
intake,thiscannotresolveallproblemsrelatedtotheuseofalessprecisemethod,Dr
GuyDeBacker(GhentUniversity,Belgium)toldheartwire .Healsoexpressed
surprisethatthelowestcategoryofsodiumintakehadanuppercutpointof<3g,
whichmakesit"impossible"toexaminetheassociationbetweenverylow(<3g/day),
low(35g/day),andhigherintakeswithCVDandtotalmortality.

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"Altogethermyviewisthatthisstudyisofinteresttoresearchersbuthaslittleimpact
onpublichealthinEurope,"hesaid."Theconclusionthatsalt-intakereductionshould
berecommendedonlytoindividualswithhypertensionandahighdietarysaltintakeis
inmyviewnotacceptabletoEuropeancommunities,wheretheactualsaltintakeison
averagebetween8and10g/day."

Theanalysisincluded133,118participants(medianage55years)drawnfromfour
prospectivestudies:ONTARGET,TRANSCEND,EPIDREAM,andtheongoingPURE.
Thelatterprovidedthebulkofthesubjectsandreportedthathigherandlowerlevelsof
sodiumexcretionareassociatedwithincreasedriskofdeathandcardiovascular
events.
ThepresentresultsarealsoinkeepingwiththerecentPREVENDstudy[2]andametaanalysis[3]alsoshowingaU-shapedassociationbetweensodiumintakeand
cardiovascularevents.
Entrenched Thinking

"Wheneveryouhaveaparadigmshift,it'snormalthatthereisresistanceandnotto
haveeveryonecomeonboardinitially,"Mentesaid."Youlookattrans-fatbackinthe
1980sandtherewasquiteabitofdatacomingoutbyanumberofinvestigatorsthat
trans-fatwasactuallyharmful,butpeopledismissedthefindings."

Hesaidthevariousorganizationsthatpushforlowsodiumbelievethetrialsthatshow
loweringsodiumreducesbloodpressureandthereforethatreducingbloodpressure
reducesCVD.But,"It'snotquitethatsimple.Thebodyismorecomplicatedthanthat."

Increasingdatashowthatreducingsodiumtolowlevelsactivatestherenin-angiotensin
system,catecholamines,andaldosterone,whichareassociatedwithincreasedCVD
eventsandmortality."Ifyoulookatmostotheressentialnutrientsthatthebodyneeds,
notjustsodium,theyallhaveaU-shapedrelationshipwithhealthmeasures,soyou
wouldn'texpectsodiumtobeanydifferent."
Also,theassociationsbetweensodiumintakeandthecompositeendpointwere
unchangedafterfurtheradjustmentforbaselineblood-pressurelevels,indicating
mechanismsunrelatedtobloodpressure.

Inaneditorialthataccompaniedthestudy[4],DrEoinO'Brien(UniversityCollege
Dublin,Ireland)writes,"Giventhedependencyofsomanyphysiologicalsystemson
thesodiumcation,itshouldcomeasnosurprisethatalow-salt-for-allpolicywould
benefitsomeanddisadvantageothers.Soratherthanallowingcontraryevidenceto
dispelthepositiveeffortsthathavebeenmadetoreducethesaltcontentoffoods,we
mustnowdirectoureffortstoformulatingapolicythatwillbenefitthemajorityinsociety
withoutcompromisingtheminority."
Randomized Data

PastAHAandAmericanSocietyofHypertensionpresidentDrSuzanneOparil
(UniversityofAlabamaatBirmingham)toldheartwire thatthepooledanalysisprovides
"moreevidencethatlowsodiumintakeisharmful."

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Criticswhoarguethatsaltintakecan'treallybemeasuredaccuratelyinpopulation
studieshaveapoint,shesaid,butaddedthatevenwhenthePUREinvestigators
validatedtheirmethods,thevalidationwascriticized.

Thecurrentbacklashismoreofthesame."It'sadefensiveresponse.Theydon'twant
tobelieveitbecauseit'stotallycontrarytowhatthey'vebeentellingeveryone."
PREVENDauthorDrMichelJoosten(UniversityMedicalCenterGroningen,the
Netherlands)toldheartwire thatthepooledanalysisisconsistentwithPUREand
observationalanalysesreportedbycoauthorDrMartinO'Donnell(NationalUniversity
ofIrelandGalway)[5],"whichmakesitamorecompellingcase,"butthatallthree
studieshadarelativelyshortfollow-upofaround4years,"whichmayhavebeentoo
shorttodevelophypertensionandsubsequentcardiovasculardiseasesordeath."

Still,pushingsodiumintaketoolowwillmostlikelyhavedetrimentalhealtheffects.The
questionremains,however,whatistoolow?"Personally,Idothinkitislowerthanthe
3gofsodium(7.5gofsalt)perdayassuggestedbytheresearchofMenteand
O'Donnell.Havingsaidthat,Ialsothinkweshouldatleastbeopentoallavailable
evidenceandkeepanopenmindaboutthetopic.Perhapswecangotoolowasfaras
sodiumreductionisconcernedinthegeneralpopulation."

Joosten,Oparil,andO'Briensuggestthattheissueofsodiumreductionmayonlybe
resolvedbyconductingarandomizedcontrolledtrial.Asapreludetosuchalarge
definitivestudy,theinvestigatorshaveinitiatedthepilotSodiumIntakeinChronic
KidneyDisease(STICK)randomizedtrialcomparingusualcarevscounselingtargeting
asodiumintakeof<2.3g/day.TheestimatedcompletiondateisMarch2018.
The authors and O'Brien report no relevant financial relationships; Mente is a recipient
of a research early career award from Hamilton Health Sciences Foundation. Other
information for the coauthors is listed in the article.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org, follow us
on Twitter and Facebook.
References

1. MenteA,O'DonnellM,RangarajanS,etal.Associationsofurinarysodium
excretionwithcardiovasculareventsinindividualswithandwithouthypertension:
apooledanalysisofdatafromfourstudies.Lancet2016;DOI:10.1016/S01406736(16)30467-6.Abstract
2. JoostenMM,GansevoortRT,MukamalKJ,etal.Sodiumexcretionandriskof
developingcoronaryheartdisease.Circulation2014;129:1121-1138.Article

3. GraudalN,JrgensG,BaslundB,AldermanMH.Comparedwithusualsodium
intake,low-andexcessive-sodiumdietsareassociatedwithincreasedmortality:
Ameta-analysis.Am J Hypertens2014;27:1129-1137.Article
4. O'BrienE.Salttoomuchortoolittle?Lancet2016;DOI:10.1016/S0140-6736
(16)30510-4.Editorial

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5. O'DonnellMJ1,YusufS,MenteA,GaoP,etal.Urinarysodiumandpotassium
excretionandriskofcardiovascularevents.JAMA2011;306:2229-2238.Article
HeartwirefromMedscape2016Medscape,LLC
Citethisarticle:StudyReopensRiftOverMeritsofLow-Sodium-for-AllPublic-Health
Policies.Medscape.May27,2016.

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