Andersons pediatric cardiology 655
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symptomsandlaboratoryabnormalitieshaveresolved.23Femalepatientsshould
stronglybecounseledregardingtheteratogeniceffectsofstatinsandtheneedfor
appropriatecontraception.
Aftertakingthestatinfor4weeks,arepeatfastinglipidprofile,alanine
aminotransferase(ALT)andaspartateaminotransferase(AST)levelsshouldbe
drawn.AriseinALTand/orASTgreaterthanorequaltothreetimestheupper
limitofnormalshouldpromptdiscontinuationofmedicationandfurther
evaluationforothercausesofliverdysfunction.IftargetLDL-Clevelsare
achievedthentherapyshouldbecontinuedwithrepeatfastinglipidprofilesand
liverenzymesat8weeksandthenevery3monthsthereafterforthefirstyear.23
WhiletheExpertPanelGuidelinesrecommendreductionofLDLtolessthan
130mg/dLwithlessthan110mg/dLconsideredanideallevel,23many
practitionersfeelmorecomfortablereducingLDLtoatleastlessthan160mg/dL
formostlower-riskpatients.Followingthefirstyearoftreatment,repeatblood
workassessmentscantakeplaceevery6months.IftargetLDL-Clevelsarenot
achieved,incrementaldosageincreasescanbemadeoranotheragent,suchas
bileacidsequestrantsorcholesterolabsorptioninhibitors(suchasezetimibe),
maybeadded(underthediscretionofalipidspecialist).23,141Readersare
directedtoarecentreviewofFHbyGiddingetal.forfurtherinformation
regardingcombinationtherapyindyslipidemia141inadditiontotheExpertPanel
Guidelines.22Whilepatientsareonstatintherapy,cliniciansshouldmonitor
growth,sexualmaturation,anddevelopment.23
ProproteinConvertaseSubtilisin/KexinType9
Inhibitors
PCSK9isahepaticproproteinthatbindstotheLDLreceptorandtargetsitfor
degradation.Thereforeitsinhibitionshouldleadtotheincreasedpresenceofthe
LDLreceptoronthecellsurface,whichinturnwouldpromotereductionsin
serumLDL-C.163ThePCSK9inhibitorsalirocumabandevolocumabwere
approvedbytheFDAfortreatmentinFHin2015.141,163Recentrandomized
trialsinadultshavedemonstratedthatPCSK9inhibitorsyieldfurtherreductions
inLDL-Cwhenaddedtostandardtherapy(includingstatins),comparedwith
standardtherapyalone.164–167ThesemedicationshavealsobeenusedinFH.In
theRUTHERFORD-2trial,331heterozygousFHsubjectsonaggressivelipidloweringtherapywererandomizedtoevolocumab140mgevery2weeks,
evolocumab420mgmonthly,orplacebo.At12weeks,theevery2-weekand
monthlydosingschedulesresultedin59%and61%reductionsinLDL-C
comparedwithplacebo,respectively.168Additionalstudieshavefurther
demonstratedtheutilityofPCSK9inhibitorsinbothheterozygous169and
homozygousFH.170PCSK9inhibitorshavealsobeenproventoreduceCV
eventsinthegeneraladultpopulationwithexistingatherosclerotic
cardiovasculardiseasewhowerealreadyreceivingstatintherapyandhadLDLClevelsgreaterthanorequalto70mg/dL.167Thisnovelclassoflipid-lowering
therapyrequiresstudyinchildrenandCVDend-pointstudiesinthegeneralFH
population.Therearenocurrentrecommendationsfortheiruseinthepediatric
population.
PharmacologicTherapyforHypertriglyceridemia
Pharmacologictherapyforchildrenwithhypertriglyceridemiaisrarelyneededin
thosethatrespondtoweightlossandlifestylechanges.However,patientsareat
riskforpancreatitiswhenlevelsexceed500mg/dL.Althoughnorandomized
clinicaltrialsofomega-3fattyacidsorfibrateshavebeenconductedinpediatric
patients,bothclassesofdrugsmaybeconsideredinyoungpatientswith
significantlyelevatedTGlevelswhodonotrespondtolifestylechanges.23A
treatmentalgorithmmodifiedfromtheExpertPanelGuidelinesforthetreatment
ofhypertriglyceridemiaisshowninFig.25.7.
FIG.25.7 Triglyceridemanagementalgorithm.aLifestylemodifications
includemaintaining25%to30%ofdailycaloriesfromfatwith<7%from
saturatedfat,about10%frommonosaturatedfat,and<200mg/dayof
cholesterolwithanavoidanceoftransfatsasmuchaspossible.In
addition,anemphasisshouldbemadetowarddecreasedsugarintake,
replacingsimplewithcomplexcarbohydrates,abstainingfromsugarsweetenedbeverages,andincreasingdietaryfishintakeinorderto
increaseomega-3fattyacids.bFemalesofchild-bearingagewhomay
becomepregnantorarepregnantshouldavoidsometypesoffishand
shellfishandshouldeatfishandshellfishthatarelowerinmercury.FLP,
Fastinglipidprofile;HDL-C,high-densitylipoproteincholesterol;LDL-C,
low-densitylipoproteincholesterol;TG,triglycerides.(ModifiedfromExpert
PanelonIntegratedGuidelinesforCardiovascularHealthandRisk
ReductioninChildrenandAdolescents;NationalHeart,Lung,andBlood
Institute.Expertpanelonintegratedguidelinesforcardiovascularhealth
andriskreductioninchildrenandadolescents:summaryreport.Pediatrics.
2011;128[suppl5]:S213–S256.)
RiskFactorClusteringandtheMetabolic
Syndrome
CVRFs,includingdyslipidemia,clusterandarestronglyassociatedwith
overweightandbodyfatness.171–173CVRFclusteringinchildhoodisassociated
withanincreasedincidenceofcardiovasculareventsinadulthood.174Obesity
andinsulinresistanceappeartobethepredominantriskfactorsforthe
developmentofaspecificformofCVRFclusteringknownasthemetabolic
syndrome.23,175Multipledefinitionsformetabolicsyndromeexistforadults.For
