Endocrinology and Metabolism Clinics of North America (Acute Endocrinology)

234 Pages·2006·3.3 MB·English

by  van den Berghe G.

Lipids
Foreword
DerekLeRoith,MD,PhD
ConsultingEditor
Thisissue,writtenbyexpertsinthefieldoflipidologyandcompiledbyDonaldSmith,
bringstothereaderbothbasicaspectsandclinicalapplicability.
An important question that often arises is the benefit of ordering more advanced
lipoprotein profiles. The main reason for the quandary, as pointed out in the article
by Lau and Smith, is that calculated low-density lipoprotein (LDL) cholesterol,
measured by standard technologies, or non–high-density lipoprotein (non-HDL)
cholesterol,arelesspredictiveofischemiccardiovascularriskthanareapolipoprotein
B(apoB)andnuclearmagneticresonance(NMR)–measuredLDLparticlesinnumerous
studies.Thisisespeciallytrueinthepresenceofhightriglycerides,orlow-HDLcholes-
terol.AlthoughapoBlevelsandthenumberofNMR-measuredLDLparticlesmaybe
morepredictive,noclinicaltrialscomparingtheuseofthesegoalsversusLDLcholes-
terolornon-HDLcholesterolgoalshavebeenperformed.Forthosewhocaninterpret
theresults, theirusemaybejustifiedoccasionally toconfirmlipid goal attainmentin
those with mixed dyslipidemias and particularly in patients already at standard lipid
goalsinthepresenceofprogressivecoronaryheartdisease.
Predictionofcoronaryheartdiseaseisextremelyimportantinclinicalpracticefor
primary and secondary prevention. Wilson emphasizes in his article the importance
of standardizing baseline measurements of the factors involved, such as the lipid
profileanddiabetesstatus,toenableoutcomestudiestoleadtodefinitivedecisions.
Ithasbeenestablished thattheFraminghamscoreisstillveryusefulasapredictive
indexexceptinJapanese-AmericansandinAfricanAmericans.Inaddition,investiga-
torsincertainEuropeancountrieshavefoundthat,whileFraminghamisuseful,itmay
overestimate cardiovascular disease in some groups, such as Italians. Future esti-
mateswillundoubtedlyaddotherbiomarkersandimagingtechniquesforatheroma-
tousburden,andeventuallymayaddgeneticmarkerstoaidinthepredictions.
Animportantaspectoflipidmanagementinvolveslifestylechanges.Katcher,Hill,
Lanford, Yoo, and Kris-Etherton comprehensively discuss dietary components
contributing to elevated LDL cholesterol, including saturated fat, trans fats, and
cholesterol. They present descriptions and clinical trial evidence of various dietary
manipulationsthatcansignificantlyalterthelipoproteinprofile,includingweightreduc-
tionanddietsthatincludemoresolublefiber,plantsterols,andsoy,allhavingvariable
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xiv Foreword
quantitativeeffects.Inaseparatesection,theeffectsoflow-carbohydrateandMedi-
terranean diets, omega 3 fatty acids, mono-unsaturated fatty acids, and alcohol on
triglycerides and HDL cholesterol are presented. Finally the lipid-altering effects of
physicalexercise arediscussed as animportant component oflifestyle change that
shouldalwayscomplementthesedietarymanipulations.
The minimal goal for reductions in LDL cholesterol is 40 mg/dL (1 mM/L). This is
oftenachievedbyasinglestatindrug,thoughoftenthepractitionerhastoconsider
additionaltherapies.HouandGoldbergdiscusstheseoptionsanddescribethemech-
anismsofactionandpracticalaspectsoftheirusage.Themajordrugsdiscussedare
statins,ezetimibe,andbileacidsequestrants,aswellasniacinandfibrates.Combi-
nationtherapieshaveindeedreducedLDLcholesterollevelsfurtherandstudiesare
ongoingtoquantifytheirpreventiveeffectsintheclinicalenvironment.
Research progresses on other new medications and other methodologies to
reduceLDLcholesterol.EvanSteinhasbeeninvolvedinmanyoftheseearly-phase
clinical trials. Hedescribes indetail compounds being studiedthat notonly provide
possible new therapies, but also illustrate the biochemistry of lipid metabolism and
thesafetyproblemsofinterferingwithit.Compoundsdiscussedincludesqualenesyn-
thaseinhibitors,apoBantisenseoligonucleotides,smallinterferingRNAsofapoB,and
proproteinconvertasesubtilismkexin9.
Venero and Thompson in their article describe the etiology and management of
statin-inducedmyopathy,animportantclinicalproblemgiventhewidespreaduseof
statins.Theincidenceasreportedinclinicaltrialsofapproximately5%islowerthan
that found in surveys of patients in clinical practice, where incidence is around
10%. The symptoms range from tolerable myalgias to fatal rhabdomyolysis in
extremely rare cases. Creatine kinase measurements may be important at baseline
withrepeattestingonlynecessarywhenthepatientactuallyexperiencesmyopathic
symptoms. Stopping the agent, reintroducing a different statin, increasing the
dosing interval, and even trying coenzyme Q10 are suggested therapeutic ways
to handle this.
IraGoldbergdiscussesthevalueoftreatinghypertriglyceridemia.Whiletreatment
ofhypercholesterolemiawithstatinsandotheragentshasshownclear-cutresultsin
preventingcardiovascularevents,andwhilethetreatmentofveryelevatedtryglycer-
idestopreventpancreatitisisimportant,thevalueoftreatingmoderatehypertriglycer-
idemia to prevent such cardiovascular events is debatable. There are numerous
dietaryregimensanddrugsthatcaneffectivelylowertriglyceridesandtheyareeffec-
tive both for very high levels (>500 mg/dL) as well as for levels below 500 mg/dL.
Despite inconsistent evidence in preventive clinical trials, lowering triglycerides to
below 150 mg/dL in patients at risk is considered a secondary lipid-altering goal,
whichoftenalsoprovidestheadditionalbenefitofraisingHDLcholesterol.
An important risk factor for the development of atheromatous cardiovascular
disease is reduced HDL cholesterol, and a few trials have shown that raising HDL
cholesterol reduces cardiovascular risk. While statins are extremely effective in
reducing LDL cholesterol, they are only mildly effective in raising HDL cholesterol.
Drugs,suchasniacin,andfibratesinthepresenceofhypertriglyceridemiaaremore
effective. Peter Toth describes efforts to find agents that will raise HDL cholesterol.
Investigators have looked into therapies involving apolipoprotein A1 (apoA1) itself,
apoA1-mimetics, novel peroxisome proliferator-activated receptor alpha agonists,
liverXreceptoralphaagonists,cholesterolestertransferproteininhibitors,andfarne-
soidXreceptorantagonists.Todatetheseagents,whiledemonstratingeffectiveness
inpreclinicalstudiesandinsomeclinicalstudies,arenotyetadequatelydevelopedfor
useinpatients.
Foreword xv
Atherosclerosis can clearly begin in childhood and adolescence. Initially it was
thoughttobepurelytheconsequenceofgeneticcauses,suchasfamilialhypercho-
lesterolemia. However, withtheepidemic of obesity thatis affectingyouth, environ-
mental factors normally involved in atherosclerosis in adults are clearly in play.
Dietary intervention and lifestyle changes are clearly indicated to reverse these
processes.Ontheotherhand,incasesoffamilialhyperlipidemiaandinthoseadoles-
centsthatfaillifestyleinterventionandareathighrisk,pharmacologicalinterventionis
clearlyindicated.ZappallaandGiddingdeveloptheseissuesintheirarticle.
NairandDarrowaddresstheimportanttopicoflipidmanagementinthegeriatric
patient.Asthepopulationages,morepatientsareatriskforcardiovasculardisease.
Such patients require lipid-lowering agents for primary and secondary prevention,
astrategythat has beenshownto work quiteeffectively in anumber of well-known
trials. Statins are particularly useful. However, when statins are inadequate as solo
agents, combinations with other lipid-altering therapies should be considered, as in
thenongeriatricagegroup.Judicioususageisessential,especiallywhenconsidering
high doses, as the elderly are more prone to the known side effects. However, this
caution should not result in avoidance of prescribing these agents to the elderly
withdyslipidemia.
Useofanti-retroviralagentsintreatingHIV-infectedindividualscommonlyresultsin
dyslipidemia. Once dyslipidemia appears, there are two therapeutic approaches:
alteringtheanti-retroviraltherapyorinitiatingtherapyforthedyslipidemia.Thesether-
apies, however, may interfere with each other, as outlined in the article by Judith
Aberg.Ifchangesinanti-retrovirals isundertakentoaffectthelipid profile,it should
bedoneundersupervisiontomaintainvirologicsuppression.Nutritionalalternatives
tolipidtherapyshouldundoubtedlybeconsideredfirst.
Chronickidneydiseaseisassociatedwithincreasedcardiovascularmorbidityand
mortality.MontagueandMurphydiscussthenotionthat,whilenumerousfactorsmay
accountforthiseffect,theroleoflipidabnormalitiesisunclear.Thisarisesfromtwo
important aspects. One is the fact that, in end-stage renal disease with patients on
dialysis,theprofileoflipidabnormalitieschangesfromthatseeninthegeneralpopu-
lation. Total cholesterol, LDL cholesterol, and HDL cholesterol may all be lower,
whereas small dense LDL particles and lipoprotein (a) may increase. Furthermore,
onlyafewclinicaltrialsusinglipid-loweringdrugshavebeencompleted,whileothers
areongoing.Allinall,theclinical-trialpreventiveevidenceisnotyetclear-cut.
Ibelievethatthisup-to-datepresentationwillbeoftremendousvalueandwillbe
mostappreciatedbyallofusinvolvedinanimportantareaofendocrinology.
Derek LeRoith, MD,PhD
Divisionof Endocrinology,Metabolism, andBoneDiseases
MountSinai School ofMedicine
OneGustave L.Levy Place
Box1055,Altran 4-36
NewYork,NY 10029,USA
E-mail address:
[email protected](D.LeRoith)
Lipids
Preface
DonaldA.Smith,MD,MPH
GuestEditor
Thefieldofclinicallipidologyhasrapidlyprogressedbeyondthesimplelipidprofileand
the highly useful and simple paradigm of the National Cholesterol Education’s Adult
Treatment Panel III and its more recent modifications. More advanced measures of
lipoprotein testing are being heavily marketed, newer risk-factor prediction models
are being tested, more data are being accumulated on the benefits of lifestyle and
pharmacologictherapiesandtherisksofthelatter,andtheuseoflipid-loweringther-
apiesareextendingtoyoungerandolderpatients,andtopatientswithrenaldiseaseor
HIVwherelipid-loweringtherapybecomesmorecomplex.Inaddition,newermedica-
tionstofurtherlowerlow-densitylipoproteincholesterolandraisehigh-densitylipopro-
teincholesterolhelpusbetterunderstandlipoproteinbiochemistryandtheenormous
creativity and difficulty required to develop a new safe and effective pharmaceutical
compound.IhavebeenextremelyprivilegedinthisissueofEndocrinologyandMetab-
olismClinicsofNorthAmericatohaveworkedandwrittenwithanextraordinarilygifted
and informed group of experts in all these areas with the hope of helping clinicians
responsible for lipid-altering therapy become more knowledgeable and thus in the
endmoreeffectiveinmanagingtheirpatients.
Donald A. Smith,MD, MPH
Associate Professorof Medicine,Community and Preventive Medicine
Zena andMichael A. Wiener CardiovascularInstitute
Marie-JoseeandHenry R.Kravis Center for Cardiovascular Health
MountSinai School ofMedicine
Box1014, 1GustaveLevy Place
NewYork,NY 10029-6574,USA
E-mail address:
[email protected] (D.A. Smith)
EndocrinolMetabClinNAm38(2009)xvii
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Advanced Lipoprotein
Testing:
Recommendations
Based on Current
Evidence
JoeF.Lau,MD,PhDa,DonaldA.Smith,MD,MPHb,*
KEYWORDS
(cid:2)Advancedlipoproteintesting (cid:2)Non-HDLcholesterol
(cid:2)ApolipoproteinB (cid:2) LDLparticlenumber (cid:2) LDLparticlesize
(cid:2)Verticaldensitygradientultracentrifugation
(cid:2)Segmentedgradientgelelectrophoresis
(cid:2)Nuclearmagneticresonancespectroscopy(NMR)
As information has emerged from recent clinical trials, it has become clear that the
incidence of ischemic atherosclerotic events is related to low-density lipoprotein
(LDL) cholesterol concentration as measured using the Friedewald equation.1 Up to
50% of secondary cardiovascular events can be prevented simply by lowering the
LDL cholesterol level to 70 to 80 mg/dL by using high-dose statin drugs.2 Because
there may be a discrepancy between the LDL cholesterol concentration and the
numberofLDLparticles,andbecausethesizeofLDLparticlesmaymodifytherisk
associated with LDL cholesterol at any concentration, it has become important to
understandbetterthemoreadvancedmethodsoflipoproteintestingforallpotential
atherogeniclipoproteins—very-low-densitylipoproteins(VLDL),intermediate-density
lipoproteins(IDL),lipoprotein(a),andLDL.Thisarticlebrieflydescribesthesemethods
and possible therapeutic target values, with special attention to target values for
patientswhohavecoronaryheartdisease(CHD).
NationalguidelineshavebeenbasedpredominantlyonLDLcholesterollevels.3–5By
examining these goals, it is possible to determine at what percentiles these LDL
cholesterol values lie within the Framingham Offspring population. One then can
look at advanced lipoprotein measures of apolipoprotein B (apoB) and the number
ofLDLparticleswithinthesamepopulationorwithinotherpopulationsrepresentative
a MountSinaiMedicalCenter,Box1030,1GustaveLevyPlace,NewYork,NY10029-6574,USA
b ZenaandMichaelA.WienerCardiovascularInstitute,Marie-JoseeandHenryR.KravisCenter
forCardiovascular Health, MountSinaiSchoolofMedicine,Box1014, 1Gustave LevyPlace,
NewYork,NY10029-6574,USA
*Correspondingauthor.
E-mailaddress:[email protected](D.A.Smith).
EndocrinolMetabClinNAm38(2009)1–31
doi:10.1016/j.ecl.2008.11.008 endo.theclinics.com
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2 Lau&Smith
oftheUnitedStatessuchastheNationalHealthandNutritionExaminationSurveyIII
(NHANES III)6 ortheMulti-Ethnic Study of Atherosclerosis (MESA) populations7 and
determinewhereequivalentpercentilegoalsfortheseparametersmightlie.Lacking
results from clinical trials to set target goals for these newer parameters, one only
canhypothesizethatincertainsubgroupsofthepopulationattainingsuchpopulation
percentile–based goals may reduce risk more effectively than simply attaining the
moreevidence-basedLDLcholesterolgoals.
MEASURESOFLIPIDTESTING
Someofthetestsavailabletocliniciansformeasuringatherogeniclipoproteinsare
1. Non–high-densitylipoprotein(non-HDL)cholesterol(fromastandardlipidprofile)
2. ApoB
3. Verticaldensitygradientultracentrifugation(VerticalAutoProfile[VAP];Atherotech)
4. Segmentedgradientgelelectrophoresis(S-GGE;BerkeleyHeartLab)
5. Nuclearmagneticresonance(NMR;Lipoprofile;Liposcience)
RefertoTable1forapartiallistoflaboratoriesthatofferadvancedlipidtestswith
theirassociatedcosts.
LOW-DENSITYLIPOPROTEINCHOLESTEROLLEVELSFROMTHESTANDARDLIPIDPROFILE
Inthestandardlipidprofile,theLDLcholesterolleveliscalculatedfromtheFriedewald
equation,8which,inthefastingstateandthuswithoutchylomicrons,isasfollows:
Total cholesterol level 5 LDLcholesterol level 1 HDL cholesterol level
1 VLDLcholesterol level
Thus
LDLcholesterol level 5 total cholesterol level(cid:3)HDL cholesterol level
(cid:3) VLDLcholesterol level
Because
VLDL cholesterol level 5 triglyceride level=5
(a good approximation when fasting triglycerides levels are < 400 mg/dL and in the
absenceoftypeIII,ordysbetalipoproteinemia),then
LDLcholesterol level 5 total cholesterol level(cid:3)HDL cholesterol level
(cid:3)triglycerides level=5
Thiscalculationallowsthetotalcholesterolandtotaltriglyceridelevelstobemeasured
enzymaticallyandrapidlyinserum,followedbyprecipitationofallapoBlipoproteinsand
enzymaticmeasurementofcholesterolinthesupernatetogivetheHDLcholesterollevel.
TheLDLcholesterolleveltheniscalculatedbytheFriedewaldequation.
NON^HIGH-DENSITYLIPOPROTEINCHOLESTEROL
Thenon-HDLcholesterollevel,thedifferencebetweentheHDLcholesterolconcentra-
tionandthetotalcholesterolconcentration,isameasureofcholesterolinallpotential
atherogenic lipoproteins including IDL, VLDL, lipoprotein (a), and LDL. It was sug-
gestedbytheNationalCholesterolEducationProgram(NCEP)asasecondarytarget
AdvancedLipoproteinTesting 3
Table1
PricesoflipidandlipoproteintestsbyvariouslaboratoriesasofSeptember2008
Laboratory Cost($)
QuestDiagnostics(800-631-1390–NewYorkCity)
Lipidprofile(standard) 75
ApoB 59
VerticalAutoProfile(VAP) 154
BerkeleyHeartLab(800-432-7889)
Lipidprofile 27
LDLgradientgelelectrophoresis(S -GGE) 51
3
ApoB 28
LipoScience(877-547-6837)
Lipoproteinsubparticlesbynuclearmagneticresonance(NMR) 80
Withstandardlipidprofile 99
inpatientswhohavetriglycerideslevelsof200mg/dLorhigher,withgoallevelsbeing
30 mg/dL greater than those for LDL cholesterol.3 This target assumes triglyceride
levels of 150 mg/dL or lower, and thus a calculated VLDL cholesterol level of
30 mg/dL or less (ie, a triglyceride level of 150 divided by 5) is a reasonable goal.
ForpatientswhohaveCHD,especiallythoseathighestrisk,4thenon-HDLcholesterol
goal is less than 100 mg/dL. The Framingham Offspring population percentiles for
NCEP III LDL cholesterol and calculated non-HDL cholesterol goals are listed in
Table2.
Table2
SuggestedLDLandnon-HDLcholesterolandapoBgoalsbasedonthreedifferentpopulations
LDLParticle
Population LDL-C Non-HDL-C ApoB Number
Percentile (mg/dL) (mg/dL) (mg/dL) (nmol/L) RiskCategory
5thpercentile 70 100 65 700 Highriskof
coronaryheart
disease
80(ADA/
ACC)51
20thpercentile 100 130 85 1000 Coronaryheart
diseaseequivalent,
diabetesmellitus
90(ADA/
ACC)51
50thpercentile 130 160 105 1300 >2cardiovascular
riskfactors
80thpercentile 160 190 125 1600 0,1cardiovascular
riskfactors
DatafromRefs.6,7,55
4 Lau&Smith
APOLIPOPROTEINB
ApoB,ameasureofallnon-HDLlipoproteins(LDL,IDL,VLDL,lipoprotein(a),andchylo-
microns[<1%ofallnon-HDLlipoproteins])9butlargelydeterminedbythenumberof
LDLparticles,canbeusedasasurrogatemeasureofLDLorthenumberofatherogenic
particlesandmaybeabettermeasureoflipoprotein-associatedatheroscleroticrisk
thantheLDLcholesterolconcentration.10Therearemanystandardizedimmunochem-
icaltechniquesformeasuringApoBlevelsinclinicallaboratories,butin1994theWorld
Health Organization, the International Federation for Clinical Chemistry, and the
CentersforDiseaseControlandPreventiondevelopedaninternationalreferencestan-
dard,SP3-07,thatreducedtheamong-methodcoefficientofvariationto6%orless,
imprecisionto5%orless,andbiascomparedwiththereferenceto6%orless.11Certi-
fied laboratories should have this level of accuracy and precision when using this
referencestandard.
ApproximatepercentilelevelsintheNHANESIIIstudyareshowninTable2.6Thus,
apoB goals corresponding to less than 70 mg/dL, less than 100 mg/dL, less than
130 mg/dL, and less than 160 mg/dL of LDL cholesterol in NHANES III population
percentiles according to this inspection of the population data would be less than
65mg/dL,lessthan85mg/dL,lessthan105mg/dL,andlessthan125mg/dL,respec-
tively.However,oneauthorityhasrecommendedthepreferencefora5mg/dLhigher
goalforApoBthanthevaluesestablishedbypopulationpercentiles(ie,agoalof<90
mg/dLforLDL-Cof<100mg/dL;apoBgoalof<110mg/dLforLDL-C<130mg/dL;
apoBgoalof<130mg/dLforLDL-C<160mg/dL;seeTable2).12
VERTICALDENSITYGRADIENTULTRACENTRIFUGATION
Based on ultracentrifugation studies at the Berkeley National Laboratories of the
University of California in 1954, HDL, VLDL,LDL, and IDLparticles were defined by
a range of migration rates measured in Svedberg units.13 The original Framingham
lipid distributions associated with this technology required 20 hours of sequential
ultracentrifugation, thus precluding the use of centrifugation in mass lipoprotein
screeningofindividuals.Amorepracticalapproach,verticaldensitygradientultracen-
trifugation, is marketed as the VAP test.14 With this method, the major lipoprotein
groups can be sorted by density into subcomponents, including four levels of LDL
andatleastthreelevelsofeachoftheothermajorlipoproteingroups.TheVAPeval-
uationincludesmeasuresofnon-HDLcholesterol,totalLDLcholesterol,anditsthree
components:lipoprotein(a)cholesterol,IDLcholesterol,and‘‘real’’LDLcholesterol.
ThepositionofthemostprominentpeakofrealLDLcholesterolisshownalongalinear
scale defining LDL particle size from large to small as patterns A, A/B, and B. The
concentrationsofeachofthefourLDLsubfractionsallowdeterminationoftherelative
percentagesofsmall,less-preferableLDL andlargeLDL particles,buttheclin-
314 112
icaluseofthisinformationhasnotbeendetermined.Lipoprotein(a),measuredasthe
cholesterolcontentinthelipoprotein(a)densitypeak,haselevatedvalueshigherthan
10mg/dL,ratherthanhigherthan30mg/dL(orhigherthan75nmol/Lusingthemore
commonantibodyassaysoflipoprotein(a)mass).15
Goals for LDL cholesterol and non-HDL cholesterol levels in VAP reports are the
sameasthegoalsintheNCEPATPIII.Practicallyspeaking,thistestyieldsveryaccu-
ratemeasuresofLDLcholesterol,eveninanonfastingstateorinthepresenceofhy-
pertriglyceridemia.ItalsoprovidesadeterminationofLDLsize.Forinstance,apatient
whohaspatternB(small)orpatternA/B(intermediate)LDLmayrequireanevenlower
LDL cholesterol goal, because the number of such small LDL particles generally is
AdvancedLipoproteinTesting 5
higherthantheLDLcholesterolconcentrationmightsuggest.Toobtainameasureof
thenumberofLDLparticles,onecouldusenon-HDLcholesterolororderanimmuno-
chemical assay of apoB, using population percentiles from Table 2 to obtain
acomparativepopulation-basedestimateofLDL-associatedrisk.
Usingnon-HDLcholesterolandsubclasslipoproteindatafromfreshserumspeci-
menswithtriglycerideslowerthan500mg/dLsenttoAtherotechforverticalultracen-
trifugation, VAP reports provide a calculated apoB level that correlates with an
immunochemical apoB assay calibrated to the international apoB standard with
acorrelationcoefficientof0.961;themeanbiasofthecalculatedvalueis3.8%higher
thanthemeasuredvalue.16ThusthisfreecalculatedapoBvaluemaybesufficiently
accuratetoavoidtheextraexpenseofanimmunochemicalassayforapoBinaddition
totheVAPtestitself.
SEGMENTEDGRADIENTGELELECTROPHORESIS
Anotherwaytoseparatelipoproteinsinvolveselectrophoresisinnon-denaturingpoly-
acrylamide gels, available from Berkeley HeartLab. Such gels form cross-linked
matricesthattraplipoproteinsandproteinsastheytraveltowardtheanode.Theoriginal
lineargelhadonlyoneconcentrationofpolyacrylamide,limitingitsseparationpower;
large lipoproteins could notenter the gel, and smaller lipoproteins traversed thegel
withoutentrapmentinthematrix.Thelatestsegmented-gradientgelsconsistofthree
gradientsinsequence,providinggreaterlipoproteinseparation ofsevensubclasses
ofLDL(LDL-S GGE)and10subclassesofHDL(HDL-S GGE).TheLDLdiameteris
3 10
givenforthetwopredominantLDLpeaks(inAngstromunits),determinedbymigration
distancescalibratedusingproteinsandlatexbeadsofknownsizes.Thepercentage
goalsgivenonthereportsforfractionforsmallLDLparticles(IIIa1b<15%andIV
b < 5%) are based on the values for the lowest coronary plaque progression rates
measuredbyquantitativecoronaryangiographyintheStanfordCoronaryRiskInter-
vention Project.17 Below-median versus above-median apoB levels of 116 mg/dL
addedtotheefficacyofGGE-measuredLDLparticlesizeinpredictingriskforangina,
myocardialinfarction(MI),andCHDdeathintheQuebecCardiovascularStudy.18Thus
bothinformationaboutthesizeofLDLparticlesobtainedfromGGEandinformation
about the number of LDL particles from apoB, which can be ordered through the
same laboratory, are important for maximizing preventive information using GGE-
measuredLDLparticlesizing.Thislaboratoryalsocanprovideotheradvancedlipopro-
teininformationincludingHDLsubclasses,lipoprotein(a),andapoEsubtypes.
NUCLEARMAGNETICRESONANCESPECTROSCOPY
Amongthelatesttechnologicaldevelopmentsisprotonnuclearmagneticresonance
(NMR) spectroscopy.19 A plasma sample is subjected to a microsecond radiofre-
quencyNMRpulse,andtheemittedspectrumofinterestreflectstheterminalmethyl
groups of the cholesterol, cholesterol esters, triglycerides, and phospholipid mole-
cules.PurelipoproteinfractionsobtainedbyGGEhavespecificNMRprofilesbased
onsize.TheseprofilesarecombinedtogivethreesizemeasurementsforVLDLand
HDL(large,intermediate,andsmall),two forLDL(largeandsmall),andoneforIDL.
The clinical report contains the number of LDL particles and levels of risk based on
percentilesintheMESApopulations.7Thelowestriskcategory(<1000nmol/L)corre-
spondsto an LDL cholesterol level lowerthan 100 mg/dL,which defines thelowest
20%ofthepopulation.Conveniently,dividingthenumberofLDLparticlesby10gives
theequivalentpopulationpercentileintheMESApopulation.Thus,onecandetermine