老年病学教学课件：Dyslipidemia in elderly

DyslipidemiainelderlyDefinitionsDyslipidemia:isadiagnosisof“abnormallipidlevels”,asmeasuredonabloodsampleandwhichreflectsoneofseveraldisordersinthemetabolismoflipoproteins.Itmaybeclassifiedsas:HypercholesterolemiaLowlevelsofhighdensitylipoproteins(HDL)Hypertriglyceridemia

NationalCholesterolEducationProgramAdultTreatmentPanelIIIApproachtoDyslipidemias1.Measurefastinglipoproteins(inmg/dL):TC(mmol/L)

<200(<5.17)Desirable200–239(5.17–6.18)Borderlinehigh≥240(≥6.20)HighLDLcholesterol

<100(<2.58)Optimal100–129(2.58–3.33)Nearoptimal/aboveoptimal130–159(3.36–4.11)Borderlinehigh160–189(4.13–4.88)High≥190(≥4.91)VeryhighHDLcholesterol

<40(<1.03)Low≥60(≥1.55)HighTG

<150(<1.695)Desirable150–199(1.695–2.249)Borderlinehigh200–499(2.26–5.639)High≥500(≥5.65)VeryhighCholesterolAfat-likesubstance(lipid)thatispresentincellmembranesandisaprecursorofbileacidsandsteroidhormones.Cholesteroltravelsinthebloodindistinctparticlescontainingbothlipidandproteinsknownaslipoproteins.Theremajorclassesoflipoproteinsarefoundintheserumofafastingindividual:lowdensitylipoproteins(LDL),highdensitylipoproteins(HDL),andverylowdensitylipoproteins(VLDL).Lipoproteinlipidparticlessurroundedbyproteinstransportcholesterolwithinthebody.Eachlipoproteinisacombinationoftriglyceride,cholesterolandproteinuniquetoitstype.LowDensityLipoprotein(LDL)iscommonlyreferredtoas“bad”cholesterol.Ittypicallymakesup60-70%ofthetotalserumcholesterolandcontainsasingleapolipoprotein,namelyapolipoproteinB(apoB).LDListhemajoratherogeniclipoproteinandhaslongbeenidentifiedbytheNationalCholesterolEducationProgram(NCEP)astheprimarytargetofcholesterolloweringtherapy;thealternateprimarytargetisapoB.Basedonevidence,manyexpertshaveconcludedthatapoBisabettertestbyprovidingabetterindicationofvasculardiseasethanLDL-C,abetterindexofhowLDLtherapyisworkingandlesslaboratoryerrorsthantheLDL-C.NotallexpertsareconvincedthatapoBshouldberoutinelymeasureandtherefore,theyareconsideredsecondaryandoptionaltargets.HighDensityLipoprotein(HDL):iscommonlyreferredtoas“good”cholesterol.Itmakesupapproximately20-30%ofthetotalserumcholesterolwithhighestlevelofprotein.HDLcholesterollevelsareinverselycorrelatedwithriskforCardiovascularDisease(CVD).SomeevidenceindicatedthatHDLprotectsagainstthedevelopmentofatherosclerosis,althoughalowHDLleveloftenreflectsthepresenceofotheratherogenicfactors.VeryLowDensityLipoprotein(VLDL)

istriglyceride-richlipoproteinandmakesup10-15%ofthetotalserumcholesterol.VLDLisproducedbytheliverandisaprecursorofLDL.VLDLremnantsappeartopromoteatherosclerosissimilartoLDL.

IntermediateDensityLipoproteins(IDL)comefromthebreakdownofVLDLandareusedtoformlowdensitylipoproteins.

Triglycerides(TG)

Anotherformoflipidinthebody.Non-lipidriskfactorsofobesity,hypertension,diabetes,andcigarettesmokingarealsointerrelatedwithtriglyceridesasareseveralemergingriskfactors(insulinresistanceglucoseintoleranceandprothromboticstate).Thus,manypersonswithelevatedtriglyceridesareatincreasedriskforCVD.Inaddition,elevatedtriglyceridesareassociatedwithotherdisorders,mostnotablypancreatitis.LIPOPROTEINCHARACTERISTICSLIPOPROTEINMAJORLIPIDSAPOLIPOPROTEINCONTENTSIZE(NMDIAMETER)DENSITY(G/ML)Chylomicrons,chylomicronremnantsApoB48,apoE,apoAI,apoAII,apoAIV,apoCII,apoCIIITriglyceridesfromdiet80-500<<1.006VLDLApoB100,apoE,apoCII,apoCIIITriglyceridesfromliver30-80<1.006IDLApoB100,apoECholesterylesters,triglycerides25-351.006-1.019LDLApoB100Cholesterylesters18-251.019-1.063HDLApoAI,apoAII,apoAVCholesterylesters,phospholipids5-121.063-1.210Lp(a)ApoB100,apo(a)Cholesterylesters~301.055-1.085RiskFactorsforDyslipidemiaMen≥40yearsoldWomen≥50yearsoldorpostmenopausalFamilyhistoryofhypercholesterolemiaorchylomicronemiaExertionalchestdiscomfortDyspneaErectiledysfunctionCigarettesmoking(currentorwithinpastyear)Abdominalobesity(men>94cmorwomen>80cm)Familyhistoryofprematurecoronaryarterydisease(CAD)Manifestationsofhyperlipidemia(xanthelasma,xanthoma,cornealarcus)Diabetesmellitus(DM)Hypertension(HTN)ChronickidneydiseaseGFR<60ml/min/1.73m2Inflammatoryconditions(systemiclupuserythematosus,rheumatoidarthritis,psoriasis)EvidenceofatherosclerosisSedentarylifestyleStressScreening

Patientsofanyagemaybescreenedatthedirectionofthephysician,particularlywhenlifestylechangesareindicated,butthefollowingrepresenttheusualrecommendations:Allmen≥40yearsofage,every1–3yearsAllwomen≥50yearsofageorpostmenopausal,every1–3yearsChildrenwithafamilyhistoryofseverehypercholesterolemiaorchylomicronemiaAllindividualswiththefollowingconditions,regardlessofageDiabetesHypertensionCurrentcigarettesmokingObesity(BMI>27kg/m2)FamilyhistoryofprematureCAD(<60yearsinfirst-degreerelatives)Inflammatorydiseases(systemiclupuserythematosis,rheumatoidarthritis,psoriasis)Chronicrenaldiseases(eGFR<60mL/min/1.73m2)EvidenceofatherosclerosisHIVinfectiontreatedwithhighlyactiveantiretroviraltherapyClinicalmanifestationsofhyperlipidemias(xanthomas,xanthelasmas,prematurearcuscornealis)ErectiledysfunctionSignsandSymptomselevatedcholesteroldoesnotleadtospecificsignsunlessithasbeenlongstanding.Xanthoma(thickeningoftendonsduetoaccumulationofcholesterol,lipiddepositsunderskinthatappearasyellowpatchesornodulesonthesurfaceoftheskin)Xanthelasmapalpabrum(yellowishpatchesaroundtheeyelids)Arcussenilis(whitediscolorationoftheperipheralcornea)Evidenceofatherosclerosis(abdominalbruits,carotidbruits,diminishedperipheralpulses,ankle-brachialindex<0.0)Symptoms

Therearenospecificsymptomsofelevatedcholesterol,butbecauseitleadstoacceleratedatherosclerosis,anumberofcardiovasculardiseasescanbetheresultofhypercholesterolemia.Anginapectoris,leadingtoCoronaryArteryBypassGrafting(CABG)MyocardialInfarction(MI)TransientIschemicAttacks(TIAs)Cerebrovascularaccidents/strokesPeripheralArteryDisease(PAD)Complications

Whentriglyceridesareelevated>10.0mmol/LindividualsareatriskfordevelopingpancreatitisHypertriglyceridemia:greaterthan11.30mmol/Lmaycauseacutepancreatitis.AlesssevereandoftenunrecognizedconditionisthechylomicronemiasyndromewhichisusuallycausedbyTGlevelsgreaterthan1000mg/dL.SymptomsofPancreatitisPaininuppermiddleorleftpartofabdomen(mayradiatetoback)SuddenpainorgraduallybuildingpainthatbecomesseverePainoftenworsensaftereatingNausea(occasionalvomiting)SwollenortenderabdomenClassification/TypeStaging

Althoughnotusedcommonlyinprimarycarefortheusualinvestigationandtreatmentofdyslipidemia,theFredricksonClassificationperformedusinglipoproteinplasmaphoresishasbeenthetraditionalandremainsthemostrigorousmethodforclassifyingdyslipidemias.TypeAverageofovernightserumElevatedparticlesAssociatedclinicaldisordersSerumTCSerumTGICreamytoplayerChylomicronsLipoproteinlipasedeficiency,apolipoprotienC-IIdeficiency↑↓↓IIaClearLDLFamilialhypercholesterolemia,polygenichypercholesterolemia,nephrosis,hypthyroidism,familialcombinedhyperlipidemia↑↑↑IIbClearLDL,VLDLFamilialcombinedhyperlipidemia↑↑↑IIITurbidIDLDysbetalipoproteinemia↑↑↑IVTurbidFamilialhypertriglyceridemia,familialcombinedhyperlipidemia,sporadichypertriglyceridemia,diabetes↑↑VCreamytop,turbidbottomChylomicrons,VLDLDiabetes↑↑↑Classificationincreasesincholesterolonly(pureorisolatedhypercholesterolemia),increasesinTGsonly(pureorisolatedhypertriglyceridemia),increasesinbothcholesterolandTGs(mixedorcombinedhyperlipidemias).Thissystemdoesnottakeintoaccountspecificlipoproteinabnormalities(eg,lowHDLorhighLDL)thatmaycontributetodiseasedespitenormalcholesterolandTGlevels.LipoproteinPatterns(FredricksonPhenotypes)PhenotypeElevatedLipoprotein(s)ElevatedLipidsIChylomicronsTGsIIaLDLCholesterolIIbLDLandVLDLTGsandcholesterolIIIVLDLandchylomicronremnantsTGsandcholesterolIVVLDLTGsVChylomicronsandVLDLTGsandcholesterolLDL=low-densitylipoprotein;TGs=triglycerides;VLDL=very-low-densitylipoprotein.Genetic(Primary)DyslipidemiasDisorderGeneticDefect/MechanismFamilialhypercholesterolemiaLDLreceptordefectDiminishedLDLclearanceFamilialdefectiveapoB-100ApoB(LDLreceptor–bindingregiondefect)DiminishedLDLclearancePCSK9gainoffunctionmutationsIncreaseddegradationofLDLreceptorsPolygenichypercholesterolemiaUnknown,possiblymultipledefectsandmechanismsLPLdeficiencyEndothelialLPLdefectDiminishedchylomicronclearanceApoC-IIdeficiencyApoC-II(causingfunctionalLPLdeficiency)FamilialhypertriglyceridemiaUnknown,possiblymultipledefectsandmechanismsFamilialcombinedhyperlipidemiaUnknown,possiblymultipledefectsandmechanismsFamilialdysbetalipoproteinemiaApoE(usuallye2/e2homozygotes)DiminishedchylomicronandVLDLclearanceGenetic(Primary)DyslipidemiasDisorderGeneticDefect/MechanismPrimaryhypoalphalipoproteinemia(familialornonfamilial)Unknown,possiblyapoA-I,C-III,orA-IVFamilialapoA/apoC-IIIdeficiency/mutationsApoAorapoC-IIIIncreasedHDLcatabolismFamilialLCATdeficiencyLCATgeneFisheyedisease(partialLCATdeficiency)LCATgeneTangierdiseaseABCA1geneFamilialHDLdeficiencyABCA1geneHepaticlipasedeficiencyHepaticlipaseCerebrotendinousxanthomatosisHepaticmitochondrial27-hydroxylasedefectBlockageofbileacidsynthesisandconversionofcholesteroltocholestanol,whichaccumulatesSitosterolemiaABCG5andABCG8genesCholesterylesterstoragediseaseandWolmandiseaseLysosomalesterasedeficiencySecondarycauses:Secondarycausescontributetomanycasesofdyslipidemiainadults.Themostimportantsecondarycauseindevelopedcountriesisasedentarylifestylewithexcessivedietaryintakeofsaturatedfat,cholesterol,andtransfats.Transfatsarepolyunsaturatedormonounsaturatedfattyacidstowhichhydrogenatomshavebeenadded;theyarecommonlyusedinmanyprocessedfoodsandareasatherogenicassaturatedfat.

Othercommonsecondarycausesincludediabetesmellitus,alcoholoveruse,chronickidneydisease,hypothyroidism,primarybiliarycirrhosisandothercholestaticliverdiseases,anddrugs,suchasthiazides,β-blockers,retinoids,highlyactiveantiretroviralagents,cyclosporine,estrogenandprogestins,andglucocorticoids.SecondarycausesoflowlevelsofHDLcholesterolincludecigarettesmoking,anabolicsteroids,HIVinfection,andnephroticsyndrome.DiagnosisDyslipidemiaisdiagnosedbymeasuringserumlipids.Routinemeasurements(lipidprofile)includetotalcholesterol(TC),TGs,HDLcholesterol,andLDLcholesterol.Lipidprofilemeasurement:TC,TGs,andHDLcholesterolaremeasureddirectly.TCandTGvaluesreflectcholesterolandTGsinallcirculatinglipoproteins,includingchylomicrons,VLDL,intermediate-densitylipoprotein(IDL),LDL,andHDL.TCvaluescanvaryby10%andTGsbyupto25%day-to-dayevenintheabsenceofadisorder.TCandHDLcholesterolcanbemeasuredinthenonfastingstate,butmostpatientsshouldhavealllipidsmeasuredwhilefasting(usuallyfor12h)formaximumaccuracyandconsistency.OthertestsPatientswithprematureatheroscleroticcardiovasculardisease,cardiovasculardiseasewithnormalornear-normallipidlevels,orhighLDLlevelsrefractorytodrugtherapyshouldprobablyhaveLp(a)levelsmeasured.Lp(a)levelsmayalsobedirectlymeasuredinpatientswithborderlinehighLDLcholesterollevelstodeterminewhetherdrugtherapyiswarranted.C-reactiveproteinmaybeconsideredinthesamepopulations.MeasurementsofLDLparticlenumberorapoproteinB-100(apoB)maybeusefulinpatientswithelevatedTGsandthemetabolicsyndrome.ApoBprovidessimilarinformationtoLDLparticlenumberbecausethereisoneapoBmoleculeforeachLDLparticle.ApoBmeasurementincludesallatherogenicparticles,includingremnantsandLp(a).Testsforsecondarycausesincludingmeasurementsoffastingglucose,liverenzymes,creatinine,thyroid-stimulatinghormone(TSH),andurinaryprotein—shouldbedoneinmostpatientswithnewlydiagnoseddyslipidemiaandwhenacomponentofthelipidprofilehasinexplicablychangedfortheworse.TreatmentRiskassessmentbyexplicitcriteriaLifestylechanges(eg,exercise,dietarymodification)ForhighLDLcholesterol,statins,sometimesbileacidsequestrants,ezetimibe,andothermeasuresForhighTG,niacin,fibrates,omega-3fattyacids,andsometimesothermeasuresGeneralprinciplesTreatmentisindicatedforallpatientswithcardiovasculardisease(secondaryprevention)andforsomewithout(primaryprevention).TheNationalInstitutesofHealth'sNationalCholesterolEducationProgram(NCEP)AdultTreatmentPanelIII(ATPIII)guidelinesarethemostcommonreferencefordecidingwhichadultsshouldbetreated(Table4:NationalCholesterolEducationProgramAdultTreatmentPanelIIIApproachtoDyslipidemiasandseeTable5:NCEPAdultTreatmentPanelIIIGuidelinesforTreatmentofHyperlipidemia).TheguidelinesfocusprimarilyonreducingelevatedLDLcholesterollevelsandsecondarilyontreatinghighTGs,lowHDL,andmetabolicsyndrome(seeMetabolicSyndrome).NewguidelineshavejustbeenpublishedbytheAmericanHeartAssociation(lateNovember2013;seeACC/AHAGuidelineontheTreatmentofBloodCholesterol)andwillbeavailableonthispageshortly.

GoalofManagementThegoalofmanagementistoreducetheriskofCardiovascularDiseaseandinthecaseofseverelyelevatedtriglycerides,topreventpancreatitis.NationalCholesterolEducationProgramAdultTreatmentPanelIIIApproachtoDyslipidemias1.Measurefastinglipoproteins(inmg/dL):TC(mmol/L)

<200(<5.17)Desirable200–239(5.17–6.18)Borderlinehigh≥240(≥6.20)HighLDLcholesterol

<100(<2.58)Optimal100–129(2.58–3.33)Nearoptimal/aboveoptimal130–159(3.36–4.11)Borderlinehigh160–189(4.13–4.88)High≥190(≥4.91)VeryhighHDLcholesterol

<40(<1.03)Low≥60(≥1.55)HighTG

<150(<1.695)Desirable150–199(1.695–2.249)Borderlinehigh200–499(2.26–5.639)High≥500(≥5.65)Veryhigh

IdentifymajorCADriskfactorsCigarettesmokingHypertension(BP≥140/90ortakingantihypertensivedrug)LowHDL(≤40mg/dL[1.03mmol/L])FamilyhistoryofprematureCAD(CADinamale1st-degreerelative<55orinafemale1st-degreerelative<65)Age(men≥45,women≥55)NCEPAdultTreatmentPanelIIIGuidelinesforTreatmentofHyperlipidemiaRiskCategoryBeginLifestyleChangesIfConsiderDrugTherapyIfLDLGoalHighCADorCADequivalents(10-yrrisk>20%)LDL≥100mg/dL(≥2.58mmol/L)LDL≥100mg/dL(≥2.58mmol/L)DrugtherapyoptionalifLDLis<100mg/dL[<2.58mmol/L])<100mg/dL<70mg/dLoptionalModeratehigh≥2riskfactorswith10-yrrisk10to20%*LDL≥130mg/dL(≥3.36mmol/L)LDL≥130mg/dL(≥3.36mmol/L)<130mg/dL<100mg/dLoptionalModerate≥2riskfactorswith10-yrrisk<10%*LDL≥130mg/dL(≥3.36mmol/L)LDL≥160mg/dL(≥4.13mmol/L)<130mg/dL<100mg/dLoptionalLower0–1riskfactorLDL≥160mg/dL(≥4.13mmol/L)LDL≥190mg/dL(≥4.91mmol/L)DrugtherapyoptionalifLDLis160–189mg/dL[4.13–4.88mmol/L])<160mg/dL危险等级TLC开始药物治疗开始治疗目标值低危：10年危险性＜5%TC≥240(6.22)LDL-C≥160(4.14)TC≥270(6.99)LDL-C≥190(4.92)TC＜240(6.22)LDL-C＜160(4.14)中危：10年危险性5-10％TC≥200(5.18)LDL-C≥130(3.37)TC≥240（6.22）LDL-C≥160(4.14)TC＜200(5.18)LDL-C＜130(3.37)高危：CHD或CHD等危症，或10年危险性10-15％TC≥160(4.14)LDL-C≥100(2.6)TC≥160(4.14)LDL-C≥100(2.59)TC＜160(4.14)LDL-C＜100(2.59)极高危：急性冠脉综合征，或缺血性心血管病合并糖尿病TC≥120(3.11)LDL-C≥80(2.07)TC≥160(4.14)LDL-C≥80(2.07)TC＜120(3.11)LDL-C＜80(2.07)Lifestylechanges

caninvolvedietandexercise.Dietarychangesincludedecreasingintakeofsaturatedfatsandcholesterol;increasingtheproportionofdietaryfiber,andcomplexcarbohydrates;andmaintainingidealbodyweight.Referraltoadietitianisoftenuseful,especiallyforolderpeople.Thelengthoftimeforwhichlifestylechangesshouldbeattemptedbeforebeginninglipid-loweringdrugsiscontroversial.Inpatientsataverageorlowcardiovascularrisk,3to6moisreasonable.

SmokingCessationThemostimportanthealthbehaviourinterventionforthepreventionofCVDResultsina36%reductionintherelativeriskofmortalityfromCADAdvisepatientswhosmoketoquitandencourageyoungpeoplenottosmoke.Providepatientswhoareunabletoquitontheirownwithinformationonsmokingcessationprograms,nicotinereplacementtherapyanddrugtherapywhereindicated.DietDecreasesodiumDecreasesimplesugarsandrefinedcarbohydratesIncreasefruitsandvegetablesIncreasewholegraincerealsIncreaseproportionofmonoandpolyunsaturatedoils,includingomega-3fattyacids.Substitutesaturatedandtransfatsforunsaturatedfats.

MaintainHealthyBodyWeightAdviseclientswithdyslipidemiawhoseBMI>25kg/m2toreducetheirweight.Optimalwaistcircumferenceformen<94cm(37in).Optimalwaistcircumferenceforwomen<80cm(32in).PhysicalActivityAtleast150minutes(30minutes/day)ofmoderateactivityConsumeAlcoholinModerationPatientswhochoosetodrinkshouldlimittheiralcoholconsumptionto2orfewerstandarddrinksperday.

Advisepatientswithelevatedtriglyceridelevelstodecreaseoreliminatealcoholconsumption.

PsychologicalFactorsStressmanagementisimportantbecausestresscanbeenidentifiedasaCVDriskfactor.DepressedpatientspostMIexperienceaworseprognosisDrugsarethenextstepwhenlifestylechangesarenoteffective.However,forpatientswithextremelyelevatedLDLcholesterol(≥190mg/dL[≥4.9mmol/L])andthoseathighcardiovascularrisk,drugtherapyshouldaccompanydietandexercisefromthestart.Classesoflipid-loweringmedicationsStatinsFibricacidderivativesCholesterolabsorptioninhibitorsNiacinBileacidsequestrants(resins)GenericNameTradeName(manufacturer)RecommendedStatinsAtorvastatinFluvastatinLovastatinPravastatinRosuvastatinSimvastatin*Lipitor(PfizerCanadaInc)Lescol(NovartisPharmaceuticalsCanadaInc)Mevacor(MerckFrosstCanadaLtd)Pravachol(Bristol-MyersSquibb)Crestor(AstraZeneca)Zocor(MerckFrosstCanadaLtd)10mg-80mg20mg–80mg20mg–80mg10mg–40mg5mg–40mg10mg–80mg*BileAcidCholestyramineColestipolEzetimibe(cholesterolabsorptioninhibitor)Questran(Bristol-Myers)Colestid(PfizerCanadaInc)Ezetrol(MerckFrosst/ScheringPharmaceuticals)2g–24g5g–30g10mgFibrates**BezafibrateFenofibrate†Gemfibrozil†‡Bezalip(ActavisGroupPTCEHF,)LipidilMicro/Supra/EZ(FournierPharmaInc,Canada)Lopid(PfizerCanadaInc)400mg48mg–200mg600mg–1200mgNiacinNicotinicacidGenericcrystallineniacinNiaspan(OryxPharmaceuticalsInc,)1g–3g0.5g–2gMonitoringLabTestFrequency/monitoringALT(alanineaminotransferase)BaselineALTlevelsRepeatbetween1and3monthsafterinitiatingstatinorniacintherapySignificantincreasesinALTlevels>3timesupperlimitofnormaloccurin0.3%-2.0%ofpatientsandaregenerallydose-related.CK(creatininekinase)BaselineCKlevelsPatientswithsignificantsymptomssofmusclediscomfortorweaknessshouldbeadvisedtoimmediatelytipstatinandreportforlabinvestigationDiscontinuedrugtherapypromptlyifmusclediscomfortorweaknessisaccompaniedbyCKlevels?>10timesupperlimitofnormalIncreasedriskofmyositisifstainsadministeredwithinteractingmedicationseg.clyclosporine,gemfibrozil,certainantifungalsandmacrolideantibioticsStatinsWelltoleratedbymostindividuals.Complaintsofmusclepain(myalgia)representmostcommonsideeffectanddoesnotnecessarilyprecludetheuseofstatinsunlessmyositisorrhabdomyolitisarepresent(thesearerare).Contraindicatedinwomenwhoareormaybecomepregnant.UselowerdoserangesinpersonsofSouthandEastAsianorigin.StatinmonotherapywillachievetargetLDL-Clevelsinmostpatients.Forpatientswithmoderatehypertriglyceridemia,theadditionofsalmonoil(1-2gthreetimesdaily)tostatintherapymaybeusefultolowertriglyceride(TG)levels;helpingtoachieveTC-HDL-Cratio.Ifclientisonanticoagulantsorlargedosesofaspirin,reducesalmonoilto1-2g/dayandwatchforbleeding.Clientshoulddiscusswithphysician.

Bileacidsequestrants

blockintestinalbileacidreabsorption,forcingup-regulationofhepaticLDLreceptorstorecruitcirculatingcholesterolforbilesynthesis.Theyareprovedtoreducecardiovascularmortality.Bileacidsequestrantsareusuallyusedwithstatinsorwithnicotinicacid(seeLowHDL)toaugmentLDLcholesterolreductionandarethedrugsofchoiceforwomenwhoareorareplanningtobecomepregnant.Bileacidsequestrantsaresafe,buttheiruseislimitedbyadverseeffectsofbloating,nausea,cramping,andconstipation.TheymayalsoincreaseTGs,sotheiruseiscontraindicatedinpatientswithhypertriglyceridemia.FibratesLowerTGsandVLDL,increaseHDL,mayincreaseLDL-C(inpatientswithhighTGs)Dietarysupplements

thatlowerLDLcholesterollevelsincludefibersupplementsandcommerciallyavailablemargarinesandotherproductscontainingplantsterols(sitosterolandcampesterol)orstanols.ThelatterreduceLDLcholesterolbyupto10%withoutaffectingHDLorTGsbycompetitivelydisplacingcholesterolfromintestinalmicelles.

NiacinInpatientswithDMorglucoseintolerance,initiatetherapyat500–100mg/dayandadjustglycemiccontrol(maycausehyperglycemia).Carefulmonitoringifgivenwithastatin.Extendedreleaseniacin(Niaspan)hassimilarefficacyandbettertolerabilitythanimmediatereleaseniacin(generic).Long-actingniacinshouldnotbeusedduetoincreasedhepatotoxicityanddecreasedefficacyCholesterolabsorptioninhibitorssuchasezetimibe,inhibitintestinalabsorptionofcholesterolandphytosterol.

usuallylowersLDLcholesterolby15to20%andcausessmallincreasesinHDLandamilddecreaseinTGs.

canbeusedasmonotherapyinpatientsintoleranttostatinsoraddedtostatinsforpatientsonmaximumdoseswithpersistentLDLcholesterolelevation.Adverseeffectsareinfrequent.Age-relatedchangesinlipoproteinmetabolism

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Longitudinalstudieshaveshownthattotalcholesterollevelsincreaseinmalesaftertheonsetofpubertyuntilage50.Thisisfollowedbyaplateauuntilage70,withtheserumcholesterolconcentrationthenfallingslightly.AlthoughithasbeensuspectedthatthelatterchangemaybeanartifactresultingfromCHDdeathsinhypercholesterolemicmen[3],themostimportantfactorinfluencingcholesterolmaybeweightchange[4].ThereductionintotalandLDLcholesterolandtheincreaseinHDL-cholesterolinoldermen,primarilyoccurinthosewholostweight,whileageisnotafactor.KeyPointsElevatedlipidlevelsareariskfactorforatherosclerosisandthuscanleadtosymptomaticcoronaryarterydiseaseandperipheralarterialdisease.Causesofdyslipidemiaincludeasedentarylifestylewithexcessivedietaryintakeofsaturatedfat,cholesterol,andtransfatsand/orgenetic(familial)abnormalitiesoflipidmetabolism.Diagnoseusingserumlipidprofile(measuredtotalcholesterol,TG,andHDLcholesterolandcalculatedLDLcholesterolandVLDL).Screeningtestsshouldbedoneatage9to11years(age2ifthereisastrongfamilyhistoryofseverehyperlipidemiaorprematureCAD;adultsarescreenedevery5yrbeginningatage20.AgerelatedchangeinlipidprofileInwomen,theserumcholesterolconcentrationisslightlyhigherthaninmenpriortoage20to25.Betweentheagesof25to55,theserumcholesterolrisesalthoughataslowerincrementalratethaninmen.Cholesterollevelsinwomenareequaltothoseofmenbetweentheagesof55to60andexceedthoseinmeninolderagegroups.AgerelatedchangeinlipidprofileTheage-relatedchangesintheserumcholesterolconcentrationprimarilyresultfromanincreaseinLDL-cholesterol(figure2)

[3].Incomparison,HDL-cholesterollevelsdonotvarymuchwithage,beingabout10mg/dL(0.26mmol/L)higherinwomenthanmen.AgerelatedchangeinlipidprofileThemechanismsresponsiblefortheprogressiveage-relatedelevationinLDL-cholesterolhavenotbeenfullyexplained;however,thedatasupportaprimaryroleforadecreaseinthefractionalcatabolicrateofLDL-cholesterol.ThisreductioninLDLcatabolismisthoughttoresultfromdiminishedactivityofhepaticLDLreceptors.ChangeinlipidlevelswithageChangesinplasmaLDL-andHDL-cholesterolconcentrationswithageinmenandwomen.LDL-cholesterollevelsrisewithage;thiseffectisinitiallymoreprominentinmenbut,byage70,LDL-cholesterollevelsarehigherinwomen.Datafrom:HeissG,TamirI,DavisCE,etal,Circulation,1980;61:302.Graphic61522Version3.0Age-relatedchangesinriskforCHDChangesinriskratio(dashedline)andattributableriskforcoronaryheartdisease(CHD)withage(solidline).Althoughtheriskratio(relativerisk)declineswithage,theincreasingprevalenceofCHDinolderpatientsresultsinanincreaseinattributable(absolute)risk.DatafromMalenka,DJ,Baron,JA,ArchInternMed1988;148:2247.Cholesterolasapredictorofcardiovascularrisk

TC=totalcholesterol;CHD=coronaryheartdisease.MartinMJetal.Lancet.1986;2:933-936;CastelliWP.AmJMed.1984;76:4-12.TC(mg/dL)6-yearCHDincidence

per1000men<204205–234235–264265–294>2950255075100125150Age-adjusted6-yearCHDmortalityper1000menTC(mg/dL)024681012141618160200260300140180220240280320MultipleRiskFactorInterventionTrial