Andriolo Adagmar , S. Azevedo Natasha Slhessarenko , Cor J.F. Fontes , Maria Eduarda Slhessarenko ,Raymundo children aged one to 13 years of Proposition decision limits for serum lipids inBrazilian ORIGINAL ARTICLE

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www.jped.com.br

ORIGINAL ARTICLE

Proposition of decision limits for serum lipids in Brazilian children aged one to 13 years ^夽,夽夽

Natasha Slhessarenko

^a^,∗

, Cor J.F. Fontes

^b

, Maria Eduarda Slhessarenko

^c

, Raymundo S. Azevedo

^d

, Adagmar Andriolo

^e

aUniversidadeFederaldeMatoGrosso(UFMT),FaculdadedeMedicina,DepartamentodePediatria,Cuiabá,MT,Brazil

bUniversidadeFederaldeMatoGrosso(UFMT),FaculdadedeMedicina,DepartamentodeClínicaMédica,Cuiabá,MT,Brazil

cFaculdadeIsraelitadeCiênciasdaSaúdeAlbertEinstein,SãoPaulo,SP,Brazil

dUniversidadedeSãoPaulo(USP),FaculdadedeMedicina,SãoPaulo,SP,Brazil

eUniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil

Received11May2017;accepted10January2018 Availableonline9March2018

KEYWORDS Children;

Adolescents;

Referenceintervals;

Decisionlimits;

Serumlipids

Abstract

Objective: Todeterminedecisionlimitsfortotalcholesterol,LDL-cholesterol,non-HDLcholes- terol, HDL-cholesterol, and triglycerides in healthychildren and adolescents from Cuiabá, Brazil.

Methods: Thiswasacross-sectionalstudyof1866healthychildrenandadolescentsrandomly selected from daycarecenters andpublic schoolsin Cuiabá. The desirablelevels ofserum lipids were deﬁned using the classic criteria,i.e., total cholesterol, LDL-cholesterol, non- HDLcholesterol,andtriglycerideslevelsbelowtheP75percentile,andHDL-cabovetheP10 percentile.

Results: ForCT,P75was:160mg/dLfortheagerangeof1to<3years,170mg/dLfor≥3to<9 years,and176mg/dLfor≥9to<13years.Fornon-HDLcholesterol,itwas122mg/dLforthe agerangeof1to<13years.ForLDL-c,itwas104mg/dLattheagerangeof1to<9yearsand 106mg/dLfrom≥9to<13years.ForTG,itwas127mg/dLfrom1to<2years;98mg/dLfrom

≥2to<6years;and92mg/dLfrom≥6to<13years.AsforHDL-cholesterol,P10was24mg/dL, 28mg/dL,32mg/dL,and36mg/dL,fortheagerangesof1to<2years,≥2to<3years,≥3to

<4years,and≥4to<13years,respectively.

Conclusion: Thedecisionlimitsfortheserumlipidlevelsdeﬁned inthisstudy differedfrom thoseobservedinthecurrentBrazilianandNorth-Americanguidelines,especiallybecauseit

夽 Pleasecitethisarticleas:SlhessarenkoN,FontesCJ,SlhessarenkoME,AzevedoRS,AndrioloA.Propositionofdecisionlimitsforserum lipidsinBrazilianchildrenagedoneto13years.JPediatr(RioJ).2019;95:173---79.

夽夽InstitutionorservicewherethestudywascarriedoutforindexingattheIndexMedicus/MEDLINE:UniversidadeFederaldeMatoGrosso, UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil.

∗Correspondingauthor.

E-mails:ronama@terra.com.br,natasha.barreto@dasa.com.br(N.Slhessarenko).

https://doi.org/10.1016/j.jped.2018.01.003

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differentiatesbetweentheageranges.Usingthesedecisionlimitsinclinicalpracticewillcer- tainlycontributetoimprovethediagnosticaccuracyfordyslipidemiainthispopulationgroup.

4.0/).

PALAVRAS-CHAVE Crianc¸as;

Adolescentes;

Intervalosde referência;

Limitesdedecisão;

Lípidesséricos

Proposic¸ãodelimitesdedecisãodoslipídeosséricosparacrianc¸asbrasileirasdeuma 13anosdeidade

Resumo

Objetivo: Determinarlimitesdedecisão(LD)paraocolesteroltotal(CT),LDL-colesterol(LDL- c), colesterol não-HDL(c-NHDL), HDL-colesterol(HDL-c) e triglicérides (TG) em crianc¸as e adolescentessaudáveisdeCuiabá.

Método: Estudo transversalenvolvendo 1.866crianc¸ase adolescentessaudáveis de creches eescolasmunicipaispúblicasdeCuiabá,aleatoriamente selecionadas.OsLD desejáveisdos lipídeosséricosforamdeﬁnidospeloscritériosclássicos,istoé,níveisdeCT,LDL-c,c-NHDL,TG abaixodopercentil75,edeHDL-cacimadopercentil10.

Resultados: OsP75paraCTforam:160mg/dLparaafaixaetáriade1a<3anos,170mg/dL para≥3a<9anose176mg/dLpara≥9a<13anos.Paraoc-NHDL,de122mg/dLnafaixa etáriade1a<13anos.LDL-c:104mg/dLnafaixaetáriade1a<9anose106mg/dLde≥9a

<13anos.TG:127mg/dLentre1a<2anos;98mg/dLde≥2a<6anos;e92mg/dLde≥6a

<13anos.QuantoaoHDL-c,oP10,foide24mg/dL,28mg/dL,32mg/dLe36mg/dL,paraas faixasetáriasde1a<2anos,≥2a<3anos,≥3a<4anose≥4a<13anos,respectivamente.

Conclusão: OsLDdosníveisséricosdelipídeosdeﬁnidosnesteestudodiferemdaquelesapre- sentadosnasdiretrizesbrasileiraseamericanasatuais,especialmenteporfazeradiferenciac¸ão entreasidades.UtilizartaisLDemnossapráticaclínicacertamentecontribuiráparamelhorar aacuráciadodiagnósticodedislipidemianessegrupopopulacional.

0/).

Introduction

Coronarydisease,secondarytoatherosclerosis,isthemain cause of current mortality.^1,2 Although it is a signiﬁcant causeofdeathinadults,atheroscleroticmanifestationsare rarely observed in children. The lifestylethat causes this diseaseusually begins in childhood, withthe ingestion of caloricfoodsandasedentarylifestyle,whichleadstoobe- sity, an important risk factor.^3---5 According to the Family Budget Survey,⁶ one in three Brazilian children aged 5---9 yearsisoverweight.Amongadolescents,thispictureisalso ofconcern.⁶

Anotherriskfactorisdyslipidemia,whoseprevalencein pediatricsisdescribedashighinBrazil,^7,8especiallyinthe ERICA⁹ (Study of Cardiovascular Risks in Adolescents), as alsoshownininternationalpublications.^2,10,11 Studiesindi- catethat50%ofchildrenwithdyslipidemiawillpresentthe diseaseduringadulthood.¹²

In Brazil, the values that deﬁne serumlipid levels for childrenandadolescentshavebeenproposedbasedonstud- iesperformed inthe NorthAmericanpediatric population for almost three decades^2,13 and are considered in the I Guidelinefor Atherosclerosis Prevention in Childhoodand Adolescence (I Diretriz sobre Prevenc¸ão da Aterosclerose na Infância e na Adolescência [IDPAIA]),³ in the I Brazil- ianGuidelinefor FamilialHypercholesterolemia(IDiretriz BrasileiradeHipercolesterolemiaFamiliar[IDBHF]),¹⁴ and,

recently, in the update of the Brazilian Guideline for Dyslipidemia and Atherosclerosis prevention (Atualizac¸ão da Diretriz Brasileira de Dislipidemias e Prevenc¸ão da Aterosclerose[ADBDPA]).¹⁵

In the IDPAIA,³ serum lipids were categorized as desirable, borderline and increased decision limits (DL), consideringtheP50,P75,andP90percentiles,respectively.

Inotherguidelines,^14,15 includingtheNorthAmerican,²the sameclassiﬁcationis equivalenttoP75,betweenP75and P95,andaboveP95.

In the ADBDPA,¹⁵ the values are described considering thepresenceorabsenceoffasting.Forserumlipids,except fortriglycerides(TG),thevaluesarethesameregardlessof fasting,andthereisonlyareferencetothedesirableDL.

Inallguidelines,lipidvaluesweredeﬁnedinasingleage range,exceptforTG,whicharepresentedintwoagegroups intheIDBHF¹⁴andtheADBDPA¹⁵:0---9yearsand10---19years.

Serumlipidmeasurementispartofthepediatricassess- ment routine.^3,14,16 Adequate interpretation of levels of total cholesterol (TC), high-density lipoprotein (HDL-c), non-high-densitylipoprotein(NHDL-c),low-densitylipoprotein (LDL-c), and triglycerides (TG) is crucial for the diagnosisofdyslipidemiaandforadequatedecision-making.

Thereportsissuedbythelaboratoriesshowthereference intervals (RIs) next tothe result,for test interpretation.

Usually,RIsareobtainedfromthetestpackageinserts,lit- eraturedata,ortheRIvalidationfromotherlaboratories;

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ideally, however, laboratories should establish their own RIs.^17,18

Establishingthelaboratory’sownRIsisanarduoustask, butitisthebestmethod,asitreﬂectsthecharacteristicsof thepopulationtowhichthetestswillbeapplieddaily.^17---19As 70%ofmedicaldecisionsarebasedonlaboratoryresults,²⁰ itisimportanttohaveadequateRIs.

Consideringthat, inBrazil,DL forserumlipidsin pedi- atricswereestablishedbasedondatafromNorthAmerican children,^3,14,15 disregarding genetic, environmental, cul- tural, and demographic differences, the present study aimedtoestablishDLforlipidsinhealthychildrenandado- lescentsinthecityofCuiabá.

Methods

The study was carried out in Cuiabá, capital city of the state of MatoGrosso. The ethniccompositionof thepop- ulationresultedfromintenserace-mixingattwodifferent moments:theﬁrstbetween populationsfromthe stateof São Paulo, Native Brazilians and blacks, during the colo- nialperiod;andthesecond,from1970onwards,whenthere wasintensemigrationoriginatingmainlyfromtheSouthand SoutheastregionsofBrazil.Themunicipalityisdividedinto fourlargeregions,whichinclude83municipalschoolsand48 municipalpublicdaycarecenters,inwhich38,934children wereenrolledin2012.²¹

Childrenandadolescentsaged1yearupto12years,11 months,and29days,enrolledinmunicipaldaycarecenters orschools ofCuiabáwereeligibleforthestudy.The num- berofclassroomsinschoolswassimilarbetweentheregions (approximately13classrooms),withapproximately30stu- dentsperroom.Thedaycarecentershadonlyoneclassand thenumberofchildrendidnotexceed15.Duetothishomo- geneity,a cluster sampling procedure wasused,withfive schoolsandfivedaycarecentersbeingchosenperregionby drawinglots.Sincenotalldaycarecentershadanursery,all fivedaycare centersthathadanurserywereaddedtothe clustersthat hadbeen drawn. Thus,a totalof 20schools and25daycarecenterswereselected.

The sample calculation wasbased onthe Clinical and Laboratory Standards Institute (CLSI) document, which recommends that at least 120 reference individuals per agegrouparenecessary todeﬁne theRI.¹⁷ Therefore,the drawing of ﬁve students/classroomwas initially proposed to meet the goal. The resulting number was 1420 students.However,tocorrecttheeffectoftheclustersample design and to compensate for losses (absence, refusal), this number was increased by 40%, which resulted in a sample of 1988 students. This sample represented 1.5%

of the population of the municipality in the study’s age group.²²

Childrenandadolescentswithoutanyknownunderlying disease,withnoclinicalsignsorsymptoms,andnohealth complaintsat thetimeof collectionwereincluded in the study.Participantsdidnotuseanytypeofmedicationona regularbasis,exceptforprophylacticferroussulfate.

Three workstations were set up in each institution: in the ﬁrststation, the questionnaire wasﬁlledout and the informed consent form was signed. Anthropometric mea- surementswereobtainedinthesecondworkstation,²³ and

blood was collected in the third workstation. The ques- tionnairecontained questions about ethnicity, which was self-reportedorcharacterizedbytherespondent.²⁴

Weight was measured using adigital scale (Bioland EB 9015,SP,Brazil)andthelength/heightwasmeasuredusing an anthropometric ruler for patients aged up to2 years, whereas older children and adolescents were measured in thestanding positionusing an anthropometer.²³ Subse- quently, these results were analyzed using age Z-scores by body mass index.²⁵ For the age range of 1---2 years, weight/length Z-scores were used.²⁵ After obtaining the Z-scoreresults,nutritional statuswasclassiﬁedasnormal weight;riskofoverweight(upto5years);overweight;obesity;severeobesity (5yearsandolder);underweight;and severeunderweight(WHOAnthroandWHOAnthroPlus,ver- sion3.2.2,WHOHeadquarters,Geneva,Switzerland).

SincetheaimofthestudywastoestablishDLsforclinical practice,itwasdecidedtoincludechildrenandadolescents fromallnutritionalcategories,providedtheydidnotshow any evidence of comorbidity. Thus, nutritional deviations werenotconsideredasanexclusioncriterion.InBrazil,33%

ofchildrenaged5---9yearsareoverweightorobese.⁵ Atotalof8mLofbloodwascollectedinasingletube.For childrenyoungerthan2years,a3-hfastwasrecommended;

forthoseaged2---5years,a6-hfast;andforthoseolderthan 5yearsandadolescents,a12-to14-hfast.

TCandTGweremeasuredusingthecolorimetricmethod and HDL-c was measured using the homogeneous colori- metric method. NHDL-c and LDL-c were estimated by calculations:NHDL-cwascalculatedbysubtractingtheHDL- c from the TC, whereas LDL-c was calculated using the Friedewaldformula.The analyseswerecarriedoutonthe Cobas 6000 equipment(Roche^®,CA, USA), at the Cedilab LaboratoryoftheDASAnetworkinCuiabá.

The statistical analysis of each serum lipid was per- formedtoestablishtheDLs.Initially,variancehomogeneity in the 12 age groups was analyzed using Bartlett’s test.

Then,the analysis of variance (ANOVA) test wasused for homogeneous variances. For non-homogeneous variances, theKruskal---Wallistestwasapplied.Subsequently,theBon- ferroniposthoctestwasused,whichadjustedthelevelof signiﬁcanceformultiplecomparisonsin2by2groups,which allowedgroupingtheageranges.

Once grouped into age ranges for each serum lipid, Bartlett’s test was repeated, and the ANOVA or Kruskal---Wallistests were applied.While keeping the age groups, outliers were excluded by calculating the mean plus or minus three standard deviations.²⁶ After outlier exclusion,the distributionwascarried outin percentiles, considering, as the classical criterion, the distribution of valuesuptoP75asdesirable.^2,14 Values ranging fromP75 toP95wereconsideredasborderlineandvalues≥P95,as elevated.These percentiles were usedfor the analysisof serumlipids,exceptHDL-c,forwhichP10wasusedasthe lowerlimit,withP50correspondingtothedesirablelevel.² Thelevelofsigniﬁcancewassetat5%(alpha=0.05).These analyses were performed using the MINITAB, version 15 (MINITABInc.,UnitedKingdom)andSPSS,version16(SPSS forWindows,Version16.0.,Chicago,USA).

Study participation occurred only after meeting the inclusioncriteriaandsigningoftheinformedconsent.The studywasapprovedbytheResearchEthicsCommitteesof

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HospitalUniversitárioJulioMuller(947/2010)andFaculdade deMedicinadaUSP(318/2011).

Results

Thesociodemographicandnutritionalcharacteristicsofthe 1866childrenandadolescentswhoparticipatedinthisstudy areshowninTable1.

FortheTCanalysis,1858childrenandadolescentswere dividedintothreeagegroups:1to<3years,≥3to<9years, and≥9to<13years.ThepercentiledistributionofTClevels isshowninFig.1A.

TheNHDL-cwasanalyzedin1854individualsinasingle agegroup,from1to<13years,whoseparametersareshown inFig.1B.ThevaluescorrespondingtoP10,P50,P75,and P95were76mg/dL,105mg/dL,122mg/dL,and150mg/dL, respectively.Chartrepresentationofthisvariablewasnot possible.

AsforLDL-c,1856childrenandadolescentswerestudied andstratiﬁedintotheagegroupsfrom1to<9yearsand≥9 to<13years(Fig.1C).

Table1 Sociodemographic and nutritional characteriza- tionof1866healthychildrenandadolescentsparticipating inthestudy,Cuiabá,MT,Brazil.2012.

Characteristic n %

Gender

Female 947 50.8

Male 919 49.2

Agerange(years)

1 181 9.7

2 248 13.3

3 280 15.0

4 162 8.7

5 168 9.0

6 177 9.5

7 152 8.1

8 150 8.0

9 112 6.0

10 114 6.1

11 65 3.5

12 57 3.1

Ethnicity(n=1854)

Mixed-race 1202 64.4

White 366 19.6

Black 233 12.5

Asian 53 2.8

Nutritionalstatus(n=1864)

Normalweight 1368 73.4

Overweight 176 9.4

Riskofoverweight 117 6.3

Obesity 92 4.9

Underweight 50 2.7

Severeobesity 38 2.1

Severeunderweight 23 1.2

Obs,variationinnduetolackofinformationforthevariable.

Forthe1839childrenandadolescentsanalyzedforTG, it was possible toidentify threeage groups of signiﬁcant variation:1to<2years,≥2to<6years,and≥6to<13years.

ThepercentiledistributionisshowninFig.1D.

Fouragegroupsweredeﬁnedfor theanalysisofHDL-c in1848individuals:1to<2years,≥2to<3years,≥3to<4 years,and ≥4to<13 years.The percentiledistribution is showninFig.1E.

The DLs found in this population for serum lipids are showninTable2.ThecomparisonofthedesirableDLsofthe present studywiththosedescribed inthedifferentguide- linesisshowninTable3.

Discussion

WhencomparingtestresultsoftheBrazilianpopulationwith DLs obtained fromother populations,erroneous interpre- tations may occur. The diagnosis of dyslipidemia can be made more accurately using DLs obtained from the local population.¹⁷

The results of this study demonstrateda difference in serumlipid levelsbetween the age groups, which is con- trary totherecommendationsofthe guidelinesthatshow DLforasinglepediatricagegroup,exceptforTG,whichis presentedindifferentlevelsfortheagegroupsof0---9years and10---19years.^14,15OnlythedesirableDLsofserumlipids willbediscussed.

RegardingTC,theDLs ofthepresentstudywerehigher thanthoseproposedbytheIDPAIA.³Intheagegroupof1---2 years,theywerelower,butidenticalintheagerangeof3---8 years,whencomparedwiththeotherguidelines.^2,14,15Inthe 9---12yearsagerange,thevaluesofthepresentstudywere higherthanthoseshownintheguidelines.^2,14,15ElevatedCT levelshavebeencorrelatedasanimportantriskfactorfor atheroscleroticcardiovasculardisease.³

Asfor NHDL-c,apowerfulpredictorof atherosclerosis, theDL obtainedinthisstudy waslowertothat suggested intheIDBH¹⁴andhigherthanthatproposedbytheNHLBI.² Theotherguidelines^3,15donotaddressthisparameter.

ForLDL-c,theDLsfoundwerelowerthanthoseproposed byalltheguidelines,^2,14,15 excepttheIDBPAIA.³Fora long time,thisparameter, togetherwithTC,wasdeemedvery importantforcardiovascularriskevaluation.

AsforTG,thisparameterisapproachedinasingleage group(2---19years)inIDPAIA,³whereasintheotherguide- lines, they are shown from 0 to 9 years and from 10 to 19years.^2,14,15Thepresentstudyproposesthedivisioninto threeagegroups.TheDLswerehigherthanthoseshownin theIDBHF¹⁴andtheNHLBI²inallagegroups.Insubjectsaged

≥2to<6yearsand≥6to<13years,thevalueswerecom- patiblewiththoseproposedintheADBDPA¹⁵withoutfasting.

WhencomparedwiththeIDPAIA,³thevaluesobtainedhere werelowerintheagegroupsfrom≥2to<6yearsandfrom

≥6 to<13years.The higherTG levelsfound inthis study in childrenaged<2yearsarecertainly due tothe shorter fastingtime.

Because of the improved accuracy of laboratory tech- niques,lipemiahasceasedtointerferewithmanylaboratory tests.Moreover,thepostprandialstate predominatesmost ofthetime;thus,themeasurementoffastingserumlipids would not reﬂect the daily mean of lipids in blood and

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Figure1 Distributionoftotalcholesterol(A),non-HDLcholesterol(B),LDL-cholesterol(C),triglycerides(D),andHDL-cholesterol levelsinmg/dL,attheP10,P50,P75,andP95percentilesintheagerangesdeﬁnedforeachanalyte.SD,standarddeviation.

would notindicate the realimpacton cardiovascularrisk assessment.²⁷Currently,theﬂexibilizationoffastingisrec- ommended,duetotheneedtoassesspatients’cardiacrisk intheirusualdietstatus.²⁸

As for HDL-c, it hasbeen observedthat itslevelstend toincreaseover the years.The evaluationof thisanalyte deservesspecialattention,sincethevalueofmedicalinter- estisthelowerlimit.TheIDBHF¹⁴adoptedP5,whereasthe NHLBI²hasadoptedP10.TheotherBrazilianguidelineshave proposedonlythedesirablevalues(P50).^3,15

HDL-c values, considering the P10, were 24mg/dL, 28mg/dL, 32mg/dL, and 36mg/dL for the four deﬁned age groups, respectively. When considering the P5, the valuesobtained were 21mg/dL, 25mg/dL,29mg/dL, and

32mg/dL.Inbothsituations,thelowerlimitvaluesfoundin thisstudywerelowerthanthoseproposedbythe IDBHF¹⁴ andtheNHLBI.²

ConsideringthedesirableDL,intheagerangeof<4years, thevaluesfoundhereinwerelowerthanthosesuggestedby theguidelines.^2,3,14,15Forthoseaged≥4years,itwashigher thanthatrecommendedbyalltheguidelines.^2,3,14,15

The serum lipid levels recommended by the Brazil- ian guidelines were observed in North American children andadolescents,withdifferentgeneticproﬁlesandeating habits,withtheaggravation ofhaving beenperformed 30 yearsago,wheneatinghabitswerebetter.2,3,13---15

Even though the information of the present study originated from a regional population, the social and

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Table2 Desirable, borderline,andaltered concentrations ofTC,NHDL-c, LDL-c, TG,andHDL-c for healthychildren and adolescentsinthemunicipalityofCuiabá,MatoGrosso,Brazil.

Biochemicalparameters(mg/dL) Agerange(years) Desirable<P75 Borderline P75to<P95

Elevated

≥P95

Totalcholesterol 1to<3 <160 160---188 ≥189

3to<9 <170 170---198 ≥199

9to<13 <176 176---204 ≥205

Non-HDLcholesterol 1to<13 <122 122---149 ≥150

LDL-cholesterol 1to<9 <104 104---131 ≥132

9to<13 <106 106---138 ≥139

Triglycerides 1to<2 <127 127---188 ≥189

2to<6 <98 98---138 ≥139

6to<13 <92 92---138 ≥139

Biochemicalparameters(mg/dL) Agerange(years) Desirable

>P50

Borderline P10toP50

Low P10

HDL-cholesterol 1to<2 >34 25---34 ≤24

≥2to<3 >39 29---39 ≤28

≥3to<4 >42 33---42 ≤32

≥4to<13 >48 37---48 ≤36

Table3 ComparisonofthedesirabledecisionlimitsforCT,HDL-c,NHDL-c,LDL-c,andTGinchildrenandadolescentsfrom theCuiabástudywiththepediatricguidelines.

Guideline Serumlipids(mg/dL)

Totalcholesterol Non-HDLcholesterol LDL-cholesterol Triglycerides HDL-cholesterol(≥P50) Presentstudy(P75) 1to<3: <160 1to<13: <122 1to<9: <104 1to<2: <127 1to<2: >34

≥3to<9: <170 ≥9to<13: <106 ≥2to<6: <98 ≥2to<3: >39

≥9to<13: <176 ≥6to<13: <92 ≥3to<4: >42

≥4to<13: >48

IDPAIA(P50) <150 --- <100 <100 ≥45

IDBHF(P75) <170 <123 <110 0to9: <75 >45

10to19: <90

ADBDPA(P75) <170 --- <110 0to9:<75

10to19:<90 >45

NHLBI(P75) <170 <120 <110 0to9: <75 >45

10to19: <90

IDPAIA,IDiretrizdePrevençãodaAterosclerosenaInfânciaenaAdolescência,2005;IDBHF,IDiretrizBrasileiradeHipercolesterolemia Familiar,2012;ADBDPA,AtualizaçãodaDiretrizBrasileiradeDislipidemiaePrevençãodaAterosclerose,2017;NHLBI,NationalHeart, LungandBloodInstitute,2012.

demographiccharacteristics ofthispopulation makethem very close to those of the rest of the Brazilian population. The current Cuiabá population resulted from an intense migratory movement. The population of Cuiabá hasincreasedfrom100,860in 1970to590,118intheyear 2017.²² Therefore,althoughregional,theassessedpopula- tionispotentially moresimilartotheBrazilianpopulation thanthoseusedforthecreationofthenationalguidelines.

Thepresentstudyhaslimitations,suchastheselection bias,asindividualsfromprivateschoolswerenotincludedin thesample.Anotherlimitationreferstotheshorterduration

offastingforyoungerchildren,whichcouldoverestimateTG values.However,aspreviouslymentioned,fastingisnotcur- rentlyrequiredtoassessthelipidproﬁle.^27,28Finally,there istheconcernabouttheexclusionofoutliers.Considering the frequency of outlier exclusion of less than 4% in the sample,²⁹ thereis littlechance theyhave interfered with theobtainedlimits,asshowninotherstudies.²⁶

Thevaluesthatallowthediagnosisofdyslipidemiasmust bereliable. Ideally, each countryshouldestablish itsown RIs and DLs.¹⁷ The values of the parametersevaluated in thepresent study mayrepresentthe DLsfor theBrazilian

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pediatricpopulation,contributingtoimprovethediagnostic accuracyinthispopulationgroup.

Funding

All exams were carried out at Diagnósticos da América, DASA,in Cuiabáandin Alphavile,SãoPaulo,at nocostto theresearchers.TheauthorreceivedagrantfromCAPES.

Conﬂicts of interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgement

The authorswould liketothanktheir esteemedprofessor CristinaJacob, forher trueteachings andinvaluablecon- tributions.

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