Professional Documents
Culture Documents
14yowhitemale
Referredafterhypercholesterolemiadetectedonroutinescreening
becauseoffathershypercholesterolemia
Totalcholesterol290mg/dl,repeat286mg/dl
Triglycerides108mg/dl,HDLcholesterol55mg/dl,LDL
cholesterol209mg/dl
Otherwisewell/Nocurrentmedications
Physicalexam,BPWNL,50thpercentileforHt/Wt
Noxanthelasma,cutaneousxanthomata,orAchillestendon
thickening
Case#1
Activity
Soccer,swimming,biking
Diet
Familyalreadyattemptingtoreducedietaryfatandcholesterol
afterlearningofelevatedcholesterolinpatientandfather
Social
Notobacco/alcohol/substanceabuse
Bothparentscomewithpatienttoclinic,seemverysupportive
Case#1
Dietaryassessment
3daydietaryrecalltodetermineaveragedailyintake
Totalcalories:2000kcal/day
Compositionas%oftotalcalories
Protein:22%
Fat:28%
Saturated:6%
Monounsaturated:14%
Polyunsaturated:8%
Carbohydrate:49%
Cholesterolcontent:221g/day
Fiber:31g/day
Case#1
53yo
MI
44yo
CH280
69yo
breastCA
42yo
CH310
35yo
healthy
CH152
36yo
healthy
CH299
6yo
healthy
CH?
68yo
diabetes
hypertension
9yo
healthy
CH?
14yo
healthy
CH286
66yo
healthy
XanthelasmaPalpebrarum
XanthomataTuberosa
Case#2
11yowhitemale
Referredafterhypercholesterolemiadetectedafterfatherwasfound
tohavehypercholestrolemiaandrecentmyocardialinfarction
Totalcholesterol254mg/dl,repeat250mg/dl
Triglycerides102mg/dl,HDLcholesterol53mg/dl,LDL
cholesterol181mg/dl
Otherwisewell/Nocurrentmedications
Physicalexam,BPWNL,50thpercentileforHt/Wt
Noxanthelasma,cutaneousxanthomata,orAchillestendon
thickening
Case#2
Activity
Computergames,TV
Biking
Diet
Somemealsathome,butoftenfastfood,snacks
Noeffortyettoalterdiet
Social
Notobacco/alcohol/substanceabuse
Parentsareseparated,liveswithmother,whoworkstwojobs
Case#2
Dietaryassessment
3daydietaryrecalltodetermineaveragedailyintake
Totalcalories:2000kcal/day
Compositionas%oftotalcalories
Protein:16%
Fat:37%
Saturated:17%
Monounsaturated:15%
Polyunsaturated:5%
Carbohydrate:47%
Cholesterolcontent:373g/day
Fiber:13g/day
Case#2
49yo
MI
59yo
hypertension
34yo
MI
34yo
CH159
healthy
36yo
CH299
MI6mosago
6yo
healthy
CH249
66yo
healthy
9yo
healthy
CH255
11yo
healthy
CH250
62yo
healthy
RiskFactorsforAtherosclerotic
HeartDisease
Hypercholesterolemia
Smoking
Hypertension
Diabetes
Sedentarylifestyle
MaleSex
FamilyhistoryofCHD
Age(male>45yoa,female>55yoa)
EvidenceRelatingDiet,SerumCholesterol
Level,andCoronaryHeartDisease
Animalstudies
Geneticdisorders,suchasfamilial
hypercholesterolemiawithelevatedserumLDL
cholesterol,areassociatedwithpremature
atherosclerosis
Epidemiologicstudies
Clinicaltrials
Autopsystudies
DietarySaturatedFatandCholesterol
IntakeandSerumTotalCholesterolin
BoysAged79YearsinSixCountries
Country
Philippines
SaturatedFat
(%ofenergy)
9.3
Cholesterol
(mg/1000kcal)
97
Italy
10.4
159
159
China
10.5
48
128
U.S.
13.5
151
167
Netherlands
15.1
142
174
Finland
17.7
157
190
SerumChol
(mg/dl)
147
SerumCholesterolinBoysandMiddleAged
MenandCHDMortalityRatesinMiddleAged
MeninIndustrializedCountries
SerumTotal
Cholesterol
(mg/dl)
BoysMen
CHDMortality
Per100,000
Menaged
4554years
Portugal
149203
71
Israel
155204
119
Italy
159200
91
Hungary
159203
276*
U.S.
167217
170
Netherlands
171221
134
Poland
176192
218*
Country
Finland
190240
264
CoronaryPrimaryPrevention
Trial(CPPT)
Hypercholesterolemic,middleagedmen
Treatedwithcholestyramine
19%reductioninfataland/ornonfatalMIover7
years
A25%reductioninserumcholesterollevel
resultedina50%reductioninCHDrisk
ControlledAngiographicTrialsof
CholesterolLowering
Severalstudiestodateinadults
Regressionoflesionsin1647%withlarge
decreasesinserumLDLcholesterollevels(34
48%reduction)for25years
Mainbenefitmaybeslowingofprogressionof
atheroscleroticlesions
WhyInterveneinChildren
Roleofhypercholesterolemiainatherosclerosiswell
establishedinadults
Childrenwithelevatedcholesterolaremorelikelytohave
familymemberswithelevatedlevelsandcomefrom
familieswithprematureatherosclerosis
Tracking
Childrenwithelevatedserumcholesterollevelsarelikelytohave
hypercholesterolemialaterinlife
Autopsystudies
AutopsyStudies
U.S.soldiersinKoreanWar(Enosetal,1955)
Grosscoronarydiseasein77%ofsubjectsstudied
Meanage22years
ConfirmedinstudiesfromVietNamWar
Holman,1961;StrongandMcGill,1962;Stary,1989
Aorticfattystreaksareextensiveinchildhood
Coronaryfattystreaksappearinadolescence
Fibrousplaquesappearintheseconddecadewithprogression
intotheseconddecade
BogalusaStudy
PDAYStudy
BogalusaStudy
N=93,239yoa
NEJM338:1650,1998
PathobiologicalDeterminantsof
AtherosclerosisinYouth(PDAY)
Multicenterpostmortemstudyin1079males,364
females,1534yearsofage
Violentdeath
Arteriesgradedforatheroscleroticlesionsinaorta
andrightcoronaryartery
Serumlipoproteinsmeasured
Serumthiocyanatemeasuredasanindexofsmoking
ArteriosclerThrombVascBiol17:95,1997
PDAYResults
Extentofsurfaceareawithfattystreaksandraisedlesions
increasedwithageinallvessels
SerumVLDLplusLDLcholesterolpositivelycorrelated
withextentoffattystreaksandraisedlesionsinallvessels
SerumHDLcholesterolnegativelycorrelatedwithextent
offattystreaksandraisedlesionsinallvessels
Smokingassociatedwithmoreextensivefattystreaksand
raisedlesionsinaorta
PediatricScreeningStrategies
Screennoone.Treateveryonewithdiet.
Screenonlythosechildrenwithapositivefamily
historyofprematureatheroscleroticdiseaseor
knownhyperlipidemia.
Screenallchildren.
NationalCholesterolEducation
Program(NCEP)Recommendations
forPediatricCholesterolScreening
Screenafter2yearsofage
Allchildrenwithfirstdegreerelativewith
symptomsordiagnosisofatheroscleroticdisease,
hyperlipidemia(serumcholesterol>240mg/dl),
orsuddencardiacdeathbefore55yearsofage
PercentageofChildrenAged019YearsWhoWouldBe
Screened,andPercentageofThosewithLDLCholesterol130
mg/dlWhoWouldBeIdentified,IfthePresenceofCVDisease
orVariousLevelsofElevatedTotalCholesterolinatLeastOne
ParentIsUsedtoSelectChildrenforScreening
ParentalCholesterol
(mg/dl)HigherThan
ChildrenWhoWould
BeScreened(%)
Sensitivityfor
Identificationof
ChildrenwithLDL
Cholesterol130mg/dl
200
63.5
86.5
220
44.3
63.5
240
25.1
40.5
260
18.3
29.7
280
15.3
28.4
300
13.9
28.4
TheLipidResearchClinicsPrevalenceStudy(N=1042)
WhattoMeasure
Totalcholesterol
Triglycerides
HDLcholesterol
CalculateLDLcholesterol
LDLcholesterol=totalcholesterolHDLcholesteroltriglycerides/5
Notaccurateiftriglycerides>400mg/dl
SomecommerciallabsnowmeasureLDLcholesteroldirectly
Fastingnotnecessaryforcholesterolmeasurementalone,
butovernightfastisrequiredforprofile
ClassificationofTotalandLDLCholesterol
LevelsinChildrenandAdolescents
Acceptable
TotalCholesterol
(mg/dl)
<170
LDLCholesterol
(mg/dl)
<110
Borderline
170199
110129
High
200
130
WhattodoAfterScreening
Iftotalcholesterol>95th%tile(200mg/dl),
repeatwithfullprofile
Ifconfirmed,ruleoutsecondarycauses
Screenfamilymembers
StartPhaseIdietandriskfactor
reduction/prevention
FollowupandconsiderPhaseIIdiettoreduce
LDLcholesteroltobelow95thpercentile
BorderlineCases
70th90thpercentile(170199mg/dl)
Repeat,ifaverageoftwostillborderline,get
completeanalysis
IfLDLcholesterolisborderline,startphaseIdiet
andriskfactorreduction/prevention
Recheckin1year
Abnormalitiesnotdetectedbya
simplecholesterolmeasurement
Hypertriglyceridemia
Hypoalphalipoproteinemia(lowHDL)
ElevatedapolipoproteinBlevelwithnormal
LDLC(excessnumberofsmallLDLparticles)
Elevatedlipoprotein(a)level
Elevatedhomocysteinelevel
SecondaryCausesofHyperlipidemia
Endocrine
Hypothyroidism
Diabetesmellitus
Glycogenstoragedisease
Pregnancy
RenalDisease
Nephroticsyndrome
Obstructiveliverdisease
Drugs
Corticosteroids,isotretinoin,thiazides,anticonvulsants,blockers,
anabolicsteroids,oralcontraceptives
FamilialAggregationof
Hyperlipidemia
Monogenic
Heterozygousfamilialhypercholesterolemia
MutationsinLDLreceptor
90%willhaveCHDby65yoa
4%ofallcasesofprematureCHD
FamilialCombinedHyperlipidemia
Expressionvariable(cholesteroland/ortriglycerideelevation)andmaybedelayed
11%ofallcasesofprematureCHD
Polygenic
AccountsformajorityofcasesofprematureCHD
Expressionofanumberofgenescontributingtohypercholesterolemiaand
atherosclerosiscombinedwithenvironmentalfactors
DietaryFatinChildrenand
AdolescentsintheUnitedStates
Age119years14%oftotalcaloriesfrom
saturatedfat
Age111years35%oftotalcaloriesfromfat
Age1219years36%oftotalcaloriesfromfat
PhaseIDiet
Nomorethan30%oftotalcaloriesfromfat
Lessthan10%oftotalcaloriesfromsaturatedfat
Lessthan300mgofcholesterol/day
Totalcaloricintakeappropriatefornormal
growthandidealbodyweight
PhaseIIDiet
Nomorethan30%oftotalcaloriesfromfat
Lessthan7%oftotalcaloriesfromsaturatedfat
Lessthan200mgofcholesterol/day
Totalcaloricintakeappropriatefornormal
growthandidealbodyweight
CriteriaforDrugTherapy
InChildrenandAdolescents
10yearsofageorolder
Adequatetrialofdietarytherapy(6mos1yr)
LDLcholesterollevel190mg/dl
LDLcholesterollevel160mg/dland
PositivefamilyhistoryofprematureCVD
or
2ormoreCVDriskfactorspersistingaftervigorous
effortstocontroloreliminatethesefactors
GoalsofDrugTherapy
inChildrenandAdolescents
AcceptableLDLcholesterollevel<130mg/dl
IdealLDLcholesterollevel<110mg/dl
Monitor6weeksafterstartingtherapy,thenevery
3monthsuntilmaximaleffect,thenevery6
months
Monitorcompliance,lipids,growth,and
appearanceofsideeffects
BileAcidSequestrants
Cholestyramine(Questran ),Colestipol(Colestid )
Onlyclassofdrugsapprovedforuseinchildrentotreat
hyperlipidemia
Bindbileacidsandenhancefecalelimination,upregulatehepaticbile
acidsynthesisfromcholesterol,andtherebyupregulatehepaticLDL
receptors
Willoftenincreaseserumtriglyceridelevelsinmixedhyperlipidemias
Notabsorbed,sideeffectsmainlyconstipation,bloating
Canlowerfatsolublevitaminandfolatelevels,butusuallynot
importantclinically
Gritty,sandyconsistency;compliancearealproblem
NCEPTreatmentGuidelines
forLDLCLevelsforAdults
Definite
Twoor
atherosclerotic moreother
disease
riskfactors
No
No
Initiation
level
(mg/dl)
>190
Goal
(mg/dl)
<160
No
Yes
>160
<130
Yes
YesorNo
>130
<100
HMGCoAReductaseInhibitors
Statins
Cerivastatin(BaycolR)
Fluvastatin(LescolR)
Atorvastatin(LipitorR)
Lovastatin(MevacorR)
Pravastatin(PravacholR)
Simvastatin(ZocorR)
Decreasehepaticcholesterolsynthesisresultinginincreased
hepaticLDLreceptorswithincreasedclearanceofplasmaLDL
particles
HMGCoAReductaseInhibitors
DecreaseserumLDLcholesterollevels
ModestincreasesinserumHDLClevels
Themorepotentstatins,atorvastatin,cerivastatin,
andfluvastatin,alsosignificantlydecrease
triglyceridelevels,possiblyservingaseffective
monotherapyinmixedhyperlipidemias
HMGCoAReductaseInhibitors
AdverseEffects
Myalgias,myopathy,rhabdomyolysis
Riskofrhabdomyolysisandacuterenalfailure
especiallyhighwithcombinedtherapywithfibric
acidderivatives,niacin,cyclosporine,
erythromycin,andazoleantifungals
Transaminaseelevation
Fetaltoxicity
Niacin
NiaspanR(extendedreleasetablets)
Ifequivalentdoseofcrystallineniacinissubstituted,
toxicitywillresult,andfulminantliverfailurehasbeen
reported
Decreasestotalcholesterol,LDLC,andtriglycerides
IncreasesHDLC
Escalatingdosetitrationtominimizesideeffects,
particularlyflushing
Niacin
AdverseEffects
Flushing
Usuallytransientandimproveswithdurationof
therapy
ASAorNSAIDpriortodosingmayminimize
Avoidingestionofalcoholorhotdrinksaroundtime
ofdosing
Ifdiscontinuedforanextendedperiod,mustescalate
andtitratedosingagain
Niacin
AdverseEffects
Transaminaseelevation
RarecasesofrhabdomyolysiswithconcomitantHMG
CoAreductaseinhibitors
Glucoseintolerance
Uricacidelevation
Monitoranticoagulanttherapy
Usewithcautioninunstableangina/recoveringMI,
especiallywithconcomitantvasoactivedrugs
FibricAcidDerivatives
Clofibrate(AtromidR),gemfibrozil(LopidR),fenofibrate
(TricorR)
Decreasetriglycerides,increaseHDLClevels
Serumtriglycerides>1000mg/dlassociatedwith
significantriskofpancreatitis
NottobeusedtotreatlowHDLCasonlylipidabnormality
Increasedincidenceofnoncoronaryandageadjustedall
causemortalityinstudies(WHO)
FibricAcidDerivatives
AdverseEffects
Myalgias,myopathy,rhabdomyolysis
Riskofrhabdomyolysisandacuterenalfailureespecially
highwithcombinedtherapywithstatins
Cholelithiasis
TransaminaseelevationandHgb/WBCdepression
Needtoreduceanticoagulantdose
Increasedriskofliverandtesticularmalignancy
Fetaltoxicity
FamilyApproachtoTreating
HyperlipidemiaandReducing
CardiovascularRisk
Affectedfamilymembersgenerallyhavesamelipid
disorder
TeamApproachSpecialistsfrompediatrics,adult
medicine,andnutrition
Programsaredesignedtofitintothefamilyroutineand
altereatinghabitsandphysicalactivity
Familiesdevelopaninternalsupportstructurewhich
improvescompliance