Category
Totalcholesterol
LDLcholesterol
Non-HDLcholesterol
Triglycerides
HDLcholesterol

Acceptable(mg/dL)
<190
<120
<150
<115
>45

Borderline(mg/dL)
190–224
120–159
150–189
115–149
40–44

Abnormal(mg/dL)
≥225
≥160
≥190
≥150
<40

ToconverttoSIunits,divideresultsby38.6fortotalcholesterol,LDLcholesterol,HDLcholesterol,
andnon-HDLcholesterol;fortriglyceridesdivideby88.6.
HDL,High-densitylipoprotein;LDL,low-densitylipoprotein.

ModifiedfromExpertPanelonIntegratedGuidelinesforCardiovascularHealthandRisk
ReductioninChildrenandAdolescents;NationalHeart,Lung,andBloodInstitute.Expertpanelon
integratedguidelinesforcardiovascularhealthandriskreductioninchildrenandadolescents:
summaryreport.Pediatrics.2011;128(suppl5):S213–S256.

Theprevious1992ExpertPanelGuidelinesrecommendedselectivescreening
fordyslipidemiabasedonthepresenceofafamilyhistoryofprematureCVD.130
However,familyhistorymaybeinaccurateandincompletefornumerous
reasons.AsystematicreviewbytheU.S.PreventiveServicesTaskForce
(USPSTF)concludedthatrelyingonfamilyhistoryforselectivescreening
wouldmissthemajorityofchildrenwithinheriteddyslipidemias,including
approximately50%ofthosewithfamilialhypercholesterolemia(FH).131
Thereforewhileapositivefamilyhistorymaybeassociatedwithincreased
CVRFandfutureCVD,anegativefamilyhistorydoesnotruleoutdyslipidemia
inchildren.23,131
Asmentionedabove,keyautopsystudieshavedemonstratedaclear
correlationbetweendyslipidemiaandtheonsetandseverityofatherosclerosisin
children,adolescents,andyoungadults.1,2Inrecentdecades,thedyslipidemic
patternsobservedinchildrenhaveevolved.Historically,thepredominant
dyslipidemiaevaluatedinpreventativecardiologyclinicswaselevatedlevelsof
LDL-C,duetoFH.Inrecentdecades,however,adyslipidemicpattern
associatedwithobesityhasbeenobservedwithincreasingfrequencyinchildren,
consistingofmoderatetosevereelevationsinTG,normaltomildelevationsin
LDL-C,andreducedHDL-C.23Theincidenceofthisformofdyslipidemiais
increasingastheincidenceofoverweight/obesityandinsulinresistance
increases.23Unfortunately,bothofthesepatternshavebeenassociatedwith
atheroscleroticlesions1,2,27,132–134anddyslipidemiashavealsobeenassociated
withendothelialdysfunctionandincreasedcIMT.132,135,136Thereforeitis
importanttoaddressdyslipidemiaearlyinlifesincenumerousstudieshave
demonstratedthatdyslipidemiatracksfromchildhoodtoadulthood.5,128,137,138



Approximatelyhalfofchildrenwithlipidlevelsabovethe75thpercentilewill
havedyslipidemiaasadults.131LipidvaluesareassociatedwithotherCVRFs,
includingobesityandfastinginsulinlevels.139Moreover,youngadultswitha
TClevelgreaterthan200mg/dLhaveafivetimesincreasedriskofhavinga
CVDevent40yearslatercomparedwithindividualswithTClessthan172
mg/dL.140
Therearemanydifferentcausesandmodifiersofdyslipidemia,including
geneticandenvironmentalfactors,nutrition,andphysicalactivity,among
others.23SecondarycausesofdyslipidemiaarelistedinTable25.7,adaptedfrom
theExpertPanelGuidelines.22Inheriteddyslipidemiasareresponsiblefora
significantproportionofpediatricdyslipidemia.Theyoccurduetoeithersinglegeneoroligogenicdefectsinvolvingseveralgenes.140FH,themostcommon
inheriteddisorder,resultsinsignificantelevationsinLDL-C,withthemorerare
homozygousformproducingdramaticincreasesinLDL-C.FHisanautosomal
dominantdisorder,involvinggenemutationseitherintheLDLreceptor(most
commonly),apolipoproteinB,orproproteinconvertasesubtilisin/kexintype9
(PCSK9).Over500mutationshavebeenidentifiedrelatedtoFHresultingina
widerangeofeffects,fromnullallelesthatblockLDL-Creceptorformationto
defectsresultingindefectivereceptorswithlimitedfunction.23HeterozygousFH
shouldbesuspectedinyouthwithanLDL-Cgreaterthan160mg/dLwithat
leastonefirst-degreerelativewithsimilarLDL-Celevations,ahistoryof
prematureCVDevents,orpositivegenetictestingforanFH-associatedgene
defect.141ChildrenwithheterozygousFHtypicallyhaveLDL-Celevations
sufficienttowarrantpharmacologictreatment.23,141WhilehomozygousFHis
veryrare(approximately1:1millionprevalence),heterozygousFHisfarmore
prevalent.Infact,recentestimatesofincidencesuggestheterozygousFHtobe
presentinapproximately1:250individuals.142,143Ahigherprevalenceisfound
incertainethnicgroups(e.g.,FrenchCanadians,Lebanese,SouthAfricans).If
leftuntreated,themedianageofonsetforfirstmyocardialinfarctionis

approximately50yearsinmalesand60yearsinwomen.141,144,145
Table25.7
DifferentialDiagnosisofSecondaryDyslipidemia
Exogenous
Alcohol

Endocrine/Metabolic
Renal
Hypothyroidism/hypopituitarism Chronicrenal
disease

Infectious
Acuteviral/bacterial


Drugtherapy

T1DMandT2DM

Corticosteroids

Pregnancy

Isoretinoin
β-Blockers
Someoralcontraceptives
Selectchemotherapeuticagents
Selectantiretroviralagents
Hepatic
Obstructiveliverdisease/cholestatic

conditions
Biliarycirrhosis
Alagillesyndrome

Polycysticovarysyndrome
Lipodystrophy
Acuteintermittentporphyria

InflammatoryDisease
Systemiclupuserythematosus
Juvenilerheumatoidarthritis

infectiona
Hemolyticuremic HIV
syndrome
Nephrotic
Hepatitis
syndrome

StorageDisease
Glycogen-storage
disease
Gaucherdisease
Cystinestorage
disease
JuvenileTaySachsdisease
Niemann-Pick
disease

Other

Kawasakidisease
Anorexianervosa
Post–solidorgan
transplantation
Childhoodcancer
survivor
Progeria
Idiopathic
hypercalcemia
Klinefeltersyndrome
Wernersyndrome

aMeasurementshouldbedelayeduntilatleast3weeksfollowingtheinfection.

T1DM,Type1diabetesmellitus;T2DM,type2diabetesmellitus.
ModifiedfromExpertPanelonIntegratedGuidelinesforCardiovascularHealthandRisk
ReductioninChildrenandAdolescents;NationalHeart,Lung,andBloodInstitute.Expertpanelon
integratedguidelinesforcardiovascularhealthandriskreductioninchildrenandadolescents:
summaryreport.Pediatrics.2011;128(suppl5):S213–S256.

HomozygousFHistypicallyassociatedwithLDL-Cvaluesexceeding400
mg/dLandisfrequentlyassociatedwithacquiredaorticvalvediseasedeveloping
undertheageof20.141CVDeventstypicallyoccurintheseconddecadeof
life.23,140ChildrenwithhomozygousFHoftenpresentwithphysical
manifestationsininfancyandearlychildhood.23Thisoftenconsistsofcutaneous
xanthomatathatmaybelocatedbetweenfingersandtoesandoverthebuttocks,
elbows,andknees,andtendinousxanthomata,typicallymostprominentinthe
Achillestendon(Fig.25.4).Completecardiacinvestigationisindicatedatthe
timeofdiagnosissinceimportantatheroscleroticdevelopmentmayhavealready
takenplace.DespiteseverelyreducedorabsentLDL-Creceptorfunction,these

patientsmayshowsomeresponsetohighdosesofstatinandcholesterol
absorptioninhibitors.23,146However,themajorityofpatientswillrequirefurther
treatments,includingtheuseofLDLapheresistoclearcirculatingLDL,
typicallyperformedbiweekly.23