Andersons pediatric cardiology 653
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FIG.25.4 Clinicalmanifestationsinhomozygousfamilial
hypercholesterolemia(FH).(A)Cutaneousxanthomaspresentonthe
elbows.(B)Interdigitalxanthomas,especiallybetweenthethumband
indexfinger,areconsideredpathognomonicforhomozygousFH.(From
GiddingSS,ChampagneMA,deFerrantiSD,etal.Theagendaforfamilial
hypercholesterolemia:ascientificstatementfromtheAmericanHeart
Association.Circulation.2015;132[22]:2167–2192.)
ManagementofPediatricDyslipidemia
WiththeexceptionofchildrenwithsevereelevationsinLDL-CorTG,theinitial
managementofchildrenwithdyslipidemiabeginswithdietarycounselingwitha
referraltoaregistereddietician.23Forchildrenandyoungadultsbetween2and
21yearsoldwithelevationsinLDL-CorTG,adietwhere25%to30%oftotal
caloriescomefromfat,withlessthanorequalto7%oftotalcaloriescoming
fromsaturatedfat(withavoidanceoftransfatswheneverpossible),
approximately10%frommonounsaturatedfats,andlessthan200mg/dayof
cholesterolisrecommended.ForchildrenwithelevationsinLDL-C,plantsterol
estersand/orplantstanolesters(whicharefoundinsomefoodssuchas
margarines)maybeused(upto2g/day)asreplacementforotherfatsourcesin
childrengreaterthan2yearsoldwithFH.Thewater-solublefiberpsylliummay
beaddedtothediet,atadoseof6g/dayforchildren2to12yearsoldand12
g/dayforchildrengreaterthanorequalto12yearsold.Forchildrenwith
elevationsinTG,familiesandchildren/adolescentsshouldbecounseledtoward
decreasedsugarintake,avoidanceofsugar-sweetenedbeverages,andreplacing
simplecarbohydrateswithcomplexones.Inaddition,forobesechildrenwith
elevationsinTG,nutritioncounselingshouldincludecaloricrestrictionand
increasedactivityasdescribedabove.Dietaryfishintakemaybeincreasedto
increaseomega-3fattyacidintake,asithasbeenshowntolowerTG
levels.147–149
StatinTherapy
StatinsinhibithydroxymethylglutarylcoenzymeAreductase,therate-limiting
enzymeinvolvedintheendogenouscholesterolsynthesispathway.23The
subsequentreductioninintracellularcholesterollevelssignalsanup-regulation
inLDL-Creceptorsynthesis,resultinginincreasedclearanceofcirculating
LDL-C.InadultswithelevatedLDL-ClevelsbutnoCVD,statintherapymay
significantlyreducethefutureincidenceofCVDevents.150Randomizedclinical
trialsandmeta-analysishavedemonstratedshort-andmedium-termsafetyand
efficacyofstatinsinloweringLDL-Cinyouth.151–156Combinationtherapyhas
alsoproveneffectiveinpediatricFHpatientssuchthatadministrationof
ezetimibe,acholesterolabsorptioninhibitor,incombinationwithsimvastatin
resultedinsignificantlygreaterreductionsinLDL-Cthansimvastatinalone.157
Inchildren,logisticalchallengespreventtheexistenceofrandomizedclinical
trialsaddressingwhethertreatingdyslipidemiasinchildhoodreduceCVDevents
laterinlife.158However,anumberofstudieshavedemonstratedimprovements
innoninvasivesurrogatemarkersofatherosclerosiswithstatintreatmentin
childrenwithFH.Forexample,aplacebo-controlledrandomizedtrial
demonstratedatrendtowardregressionincIMTinpravastatin-treatedFH
subjects,whereastheplacebogroupdemonstratedatrendtowardsprogression
overthecourseof2years(Fig.25.5).21Afollow-upassessmentofthisstudy
populationdemonstratedthatearlierinitiationofpravastatinwasanindependent
predictorofcIMTatfollow-up.159Anotherplacebo-controlledrandomizedtrial
ofchildrenwithFHdemonstratedimprovementsinFMDwithsimvastatin
treatment,withFMDlevelsinthetreatmentgroupimprovingtoalevelsimilar
toanormalcontrolgroup.20Inaddition,arecentstudydemonstratedaslowing
ofprogressionofcIMTinchildrenwithFHtreatedwithrosuvastatinfortwo
years,suchthattheircIMTafter2yearswasnotsignificantlydifferentfromtheir
unaffectedsiblings.160
FIG.25.5 Meancarotidintima-mediathickness(IMT)changesin
pravastatin-andplacebo-treatedchildrenwithfamilial
hypercholesterolemia.Errorbarsindicatestandarderror.Pravastatin
treatmentdemonstratedtrendstowardscarotidIMTregressionwhile
placebotreatmentresultedintrendstowardcarotidIMTprogression.
(ModifiedfromWiegmanA,HuttenBA,deGrootE,etal.Efficacyand
safetyofstatintherapyinchildrenwithfamilialhypercholesterolemia:a
randomizedcontrolledtrial.JAMA.2004;292[3]:331–337.)
Adverseeffectsresultingfromstatinusearerarebutincludemyopathyand
hepaticenzymeelevation.Rhabdomyolysisisanextremelyrareoccurrencein
adultsonstatintherapy,withanincidencereportedat3per100,000personyears.23However,rhabdomyolysishasnotoccurredinthepediatrictrialstodate.
Inadults,musclecomplaintsarefrequentlyreportedbutneweranalysessuggest
theseeffectsoccurwithnomorefrequencyinthedruggroupversustheplacebo
groupwhensubjectsareadequatelyblindedtotreatmentgroup.161Furthermore
therehasnotbeenanydemonstratedimpactongrowth,development,orsexual
maturationidentified.23AsystematicreviewofstatinuseinchildrenwithFH
foundnodifferencebetweenstatin-treatedandplacebo-treatedchildren
regardingadverseevents,sexualdevelopment,ormuscleandlivertoxicity.156
Statintherapyisthefirstlinemedicationtobeusedinpatientswith
sufficientlyelevatedLDL-Cornon-HDL-Clevels.23AnLDL-Cgreaterthanor
equalto190mg/dLonatleasttwooccasionsinachildwithnohistoryofearly
CVDwhohasnotrespondedsufficientlytolifestylemodificationmeetsthe
recommendationforinitiationofpharmacologictherapy.Higherriskyouth
