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The patient with chronic renal insufficiency has hypertension that is usually partially volume
dependent.Retentionofsodiumandwaterexacerbatestheexistinghypertensivestate,anddiureticsare
importantinthemanagement ofthisproblem. WhenestimatedGFRis<30–35mL/min/1.73m2,loop
diureticsarethemosteffectiveclass. Inthepresenceofproteinuria,ACEinhibitors/ARBsshouldbe
consideredbecausehigherurinaryexcretionofproteinisassociatedwithamorerapiddeclineinGFR,
regardless of the cause ofrenal insufficiency. More recently, anupdated Kidney Disease Improving
GlobalOutcomesBPguidelinerecommendedmoreintensiveBPcontrolwithasystolictargetof<120
mmHgfor all patients with CKDnotondialysis.45 Data from the SPRINT trial seemed to indicate
higher rates of acute kidney injury with intensive treatment for patients with stage 3 or 4 CKD.
46
However,subsequentanalysesofSPRINTandfindingsfromasubstudyhaveshownthatthesechanges
were likelybenign andhemodynamic rather than causing permanentinjury.
47-49
Longer-term data are
neededforclarificationandconfirmationofthesefindings.
ThehypertensivepatientwithLVHisatincreasedriskforsuddendeath,MI,andall-causemortality.
Although there is no direct evidence, regression of LVH could be expected to reduce the risk for
subsequent complications. Aggressive BP control and renin–angiotensin system blockade with ACE
inhibitors/ARBsappeartohavethegreatesteffectontheregression.
50-52
The hypertensive patient with CAD is at increased risk for unstable angina (UA) and MI. βAdrenergic antagonists can be used as first-line agents in these patients because they can decrease
cardiacmortalityandsubsequentreinfarctioninthesettingofacuteMIandcandecreaseprogressionto
MIinthosewhopresentwithUA.β-Adrenergicantagonistsalsohavearoleinsecondarypreventionof
cardiaceventsandincreasinglong-termsurvivalafteranMI. Careshouldbe exercisedinthosewith
cardiacconductionsystemdisease.ACEinhibitorsare beneficialinpatientswithCADanddecrease
mortalityinindividualswhopresentwithacuteMI,especiallythosewithleftventriculardysfunction.
53-
56
Thehypertensivepatientwithheartfailurewithreducedejectionfraction(HFrEF)isatriskfor
progressive left ventricular dilatation and sudden death. Patients should be prescribed guidelinedirected medical therapy to attain a BP <130/80 mm Hg (see Chapter 5, Heart Failure and
Cardiomyopathy). In this population,ACEinhibitors decrease mortality,54 andinthe settingof acute
MI,theydecreasetheriskofrecurrentMI,hospitalizationforHF,andmortality.57ARBshavesimilar
beneficialeffects,andtheyappeartobeaneffectivealternativeinpatientswhodonottolerateanACE
inhibitor.33 Several recent studieshavesupported the useofARNI over ACEinhibitors or ARBs in
HFrEF patients as sacubitril–valsartan (ARNI) was shown to reduce all-cause and cardiovascular
mortality and HF hospitalization rate when compared head-to-head to enalapril (ACE inhibitor).
36
ARNItherapyalsolikelyhasbeneficialeffectsonrenalfunctionandglucosecontrol,basedonrecent
emerging data.
37-39
β-Adrenergic antagonist therapy has also been shown to decrease morbidity and
mortality. Agents shown to have proven benefit include metoprolol succinate, carvedilol, and
bisoprolol.
29,58,59
Nitrates andhydralazinealsodecreasemortalityinspecificsubsetsofpatientswith
HFirrespectiveofhypertension,buthydralazinecancausereflextachycardiaandworseningischemia
in patients with unstable coronary syndromes and should be used with caution. Mineralocorticoid
receptor antagonists have been shown to decrease mortality in patients with HFrEF.
Nondihydropyridinecalciumchannelantagonistsshouldgenerallybeavoided.
Thehypertensivepatientwithheartfailurewithpreservedejectionfraction(HFpEF)maypresent
withsignsofvolumeoverloadandthusdiureticsmaybeusedasinitialtherapy.Theoptimaltreatment
regimenforhypertension inpatients with HFpEFis unclear. ACEinhibitors/ARBshavethe greatest
effectonregressionofLVHandthusmayimprovediastolicfunction.
60
Inthepregnantpatientwithhypertension,thereisconcernforpotentialmaternalandfetalmorbidity
andmortalityassociatedwithelevatedBPandtheclinicalsyndromesofpreeclampsiaandeclampsia.
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The possibility of teratogenic or other adverse effects of antihypertensive medications on fetal
developmentshouldalsobeconsidered.
Classification of hypertension during pregnancy has been proposed by the American College of
ObstetricsandGynecology.
61
Preeclampsia–eclampsia: Diagnosis is established ifthere is new-onset hypertensionafter 20
weeksofgestationandthepresenceofproteinuria.ElevatedSBP≥140mmHgorDBP≥90mm
Hg ontwo occasionsatleast4hoursapartoraone-time measurementofSBP≥160mmHgor
DBP≥110mmHgqualifiesashypertension.Ifnoproteinuriaispresent,thenhypertensionalong
with oneof the followingqualifies: platelets <100,000/μL, creatinine>1.1 mg/dL (or doubling
from baseline), liver transaminases greater than twice the normal, pulmonary edema, or
cerebral/visual symptoms. Eclampsia encompasses these parameters in addition to generalized
seizures.
Chronic (preexisting) hypertension: This disorder is defined as hypertension diagnosed or
presentbefore pregnancyor 20 weeksof gestation(traditionally, a BP≥140/90mm Hgwithat
leasttwodeterminationsatleast4hoursapartisused).
Chronic hypertension with superimposed preeclampsia: This classification is used when a
womanwithchronic hypertensiondevelops worseninghypertension andnew proteinuriaand/or
otherfeaturesofpreeclampsiaasoutlinedpreviously.
Gestationalhypertension:ThisdisorderisdefinedbyaBP≥140/90mmHgafterthe20thweek
ofpregnancywithoutproteinuriaorotherfeaturesofpreeclampsia.
Therapy: Treatment of hypertensioninpregnancyis recommended when SBP is ≥160 mmHgor
DBPis≥100mmHg;however,clinicaljudgmentshouldbeusedindeterminingtreatmentinpregnant
womenwithcomorbidconditionssuchasCVDorCKD.
Nonpharmacologictherapy,suchasweightreductionandvigorousexercise,isnotrecommended
duringpregnancy.
Alcoholandtobaccouseshouldbestronglydiscouraged.
Pharmacologicinterventionwithlabetalol,nifedipine,ormethyldopaisrecommendedasfirst-line
therapybecauseoftheirprovensafety.
ACE inhibitors and ARB have been proven to be teratogenic and increase fetal morbidity or
mortality.
β-Blockersmaybeusedinpregnancy;however,atenololshouldnotbeusedduetoincreasedrisk
offetalgrowthrestriction.
Ifapatientissuspectedofhavingpreeclampsiaoreclampsia,urgentevaluationisrecommended.
MAOIs:MAOIsusedinassociationwithcertaindrugsorfoodscanproduceacatecholamineexcess
stateandacceleratedhypertension.Interactionsarecommonwithtricyclicantidepressants,meperidine,
methyldopa, levodopa, sympathomimetic agents, and antihistamines. Tyramine-containing foods that
canleadtothissyndromeincludecertaincheeses,redwine,beer,chocolate,chickenliver,processed
meat, herring, broad beans, canned figs, andyeast. Nitroprusside, labetalol, and phentolamine have
been used effectively in the treatment of accelerated hypertension associated with MAOI use (see
Table3-5).
Complications
Withdrawalsyndromeassociatedwithdiscontinuationofantihypertensivetherapy:Whensubstituting
therapyinpatientswithmoderatetoseverehypertension,itisreasonabletoincreasedosesofthenew
medicationinsmallincrementswhiletaperingthepreviousmedicationtoavoidexcessiveBP
fluctuations.Onoccasion,anantihypertensivewithdrawalsyndrome(AWS)develops,usuallywithinthe
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first24–72hours,whenBPrisestolevelsthataremuchhigherthanthoseofbaselinevalues.Themost
severecomplicationsofAWSincludeencephalopathy,stroke,MI,andsuddendeath.AWSismost
commonlyassociatedwithcentrallyactingadrenergicagents(particularlyclonidine)andβ-adrenergic
antagonistsbuthasbeenreportedwithotheragentsaswell,includingdiuretics.Discontinuationof
antihypertensivemedicationsshouldbedonewithcautioninpatientswithpreexistingcerebrovascularor
cardiacdisease.ManagementofAWSbyreinstitutionofthepreviouslyadministereddrugisgenerally
effective.
Dyslipidemia
GENERALPRINCIPLES
Lipidsaresparinglysolublemacromoleculesthatincludecholesterol,fattyacids,andtheirderivatives.
Plasmalipids are transported bylipoproteinparticles composed ofapolipoproteins, phospholipids,
freecholesterol,cholesterolesters,andtriglycerides.
Humanplasmalipoproteinsareseparatedintofivemajorclassesbasedondensity:
Chylomicrons(leastdense)
Very-low-densitylipoproteins(VLDLs)
Intermediate-densitylipoproteins(IDLs)
Low-densitylipoproteins(LDLs)
High-densitylipoproteins(HDLs)
A sixth class, lipoprotein(a) [Lp(a)], resembles LDL in lipid composition and has a density that
overlapsLDLandHDL.
PhysicalpropertiesofplasmalipoproteinsaresummarizedinTable3-6.
TABLE3-6
PHYSICALPROPERTIESOFPLASMALIPOPROTEINS
A
Lipoprotein Lipid
Composition
Origin Apolipoproteins
Chylomicrons TG,85%;chol,3% Intestine A-I,A-IV;B-48;C-I,C-II,C-III;
E
VLDL TG,55%;chol,
20%
Liver B-100;C-I,C-II,C-III;E
IDL TG,25%;chol,
35%
Metabolicproductof
VLDL
B-100;C-I,C-II,C-III;E
LDL TG,5%;chol,60% MetabolicproductofIDL B-100
HDL TG,5%;chol,20% Liver,intestine A-I,A-II;C-I,C-II,C-III;E
Lp(a) TG,5%;chol,60% Liver B-100;Apo(a)
Chol,cholesterol;HDL,high-densitylipoprotein;IDL,intermediate-densitylipoprotein;LDL,low-densitylipoprotein;Lp(a),
lipoprotein(a);TG,triglyceride;VLDL,very-low-densitylipoprotein.
a
Remainderofparticleiscomposedofphospholipidandprotein.
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Nearly 90% of patients with congestive heart disease (CHD) have some form of dyslipidemia.
Increased levels of LDL cholesterol (LDL-C), remnant lipoproteins, Lp(a), anddecreased levels of
HDLcholesterolhaveallbeenassociatedwithanincreasedriskofprematurevasculardisease.
62,63
In
addition,dyslipidemia is highly prevalent inchildrenwith nonalcoholic fatty liver disease and may
playaroleinitspathophysiology.
64
Clinicaldyslipoproteinemias
Mostdyslipidemiasaremultifactorialinetiologyandreflecttheeffectsofgeneticinfluencescoupled
with diet, inactivity, smoking, alcoholuse,andcomorbid conditions such as obesity and diabetes
(DM).
DifferentialdiagnosisofthemajorlipidabnormalitiesissummarizedinTable3-7.
TABLE3-7
DIFFERENTIALDIAGNOSISOFMAJORLIPIDABNORMALITIES
LipidAbnormality PrimaryDisorders SecondaryDisorders
Hypercholesterolemia Polygenic,familial
hypercholesterolemia,familial
defectiveapoB-100;PCSK9
gain-of-functionmutation
Hypothyroidism,nephrotic
syndrome,anorexianervosa
Hypertriglyceridemia Lipoproteinlipasedeficiency,apo
C-IIdeficiency,apoA-V
deficiency,familial
hypertriglyceridemia,
dysbetalipoproteinemia
Diabetesmellitus,obesity,
metabolicsyndrome,alcoholuse,
oralestrogen,renalfailure,
hypothyroidism,retinoicacid,
lipodystrophies
Combined
hyperlipidemia
Familialcombinedhyperlipidemia,
dysbetalipoproteinemia
Diabetesmellitus,obesity,
metabolicsyndrome,nephrotic
syndrome,hypothyroidism,
lipodystrophies
LowHDL Familial
hypoalphalipoproteinemia,Tangier
disease(ABCA1deficiency),
apoA1mutations,lecithin–
cholesterolacyltransferase
deficiency
Diabetesmellitus,obesity,
metabolicsyndrome,
hypertriglyceridemia,smoking,
anabolicsteroids
apo,apolipoprotein;HDL,high-densitylipoprotein.
ThemajorgeneticdyslipoproteinemiasarereviewedinTable3-8.
65,66
Familial hypercholesterolemia (FH) and familial combined hyperlipidemia are disorders that
contributesignificantlytoprematureCVD.
TABLE3-8
REVIEWOFMAJORGENETICDYSLIPOPROTEINEMIAS
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TypeofGenetic
Dyslipidemia
TypicalLipidProfile TypeofInheritance
Pattern
PhenotypicFeatures
Familial
hypercholesterolemia
Increased LDL
cholesterol
(>190mg/dL)
Homozygous form
or compound
heterozygous form
(rare)canhaveLDL
cholesterol >500
mg/dL
Autosomaldominant
(prevalenceof1in
200–250for
heterozygoteformand
1in250,000for
homozygousform)
PrematureCAD
Tendonxanthomas
Premature arcus
corneae (full arc
beforeage40)
Homozygous form:
planar and tendon
xanthomas andCAD
in childhood and
adolescence
Familialcombined
hyperlipidemia
High levels of
VLDL,LDL,orboth
LDL apo B-100
level>130mg/dL
Autosomaldominant
(prevalenceof1%–
2%)
PrematureCAD
Patients do
develop tendon
xanthomas
Familial
dysbetalipoproteinemia
Symmetric
elevations of
cholesterol and
triglycerides (300–
500mg/dL)
Elevated VLDL-totriglyceride ratio
(>0.3)
Autosomalrecessive
PrematureCAD
Tuberous or
tuberoeruptive
xanthomas
Planar xanthomasof
the palmar creases
are essentially
pathognomonic
Familial
hypertriglyceridemia
(canresultin
chylomicronemia
syndrome)
Most patients have
triglyceridelevelsin
the range of 150–
500mg/dL
Clinical
manifestations may
occur when
triglyceride levels
Familial
hypertriglyceridemia
is an autosomal
dominant disorder
caused by
overproduction of
VLDL triglycerides
and manifests in
Eruptivexanthomas
Lipemiaretinalis
Pancreatitis
Hepatosplenomegaly
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exceed1500mg/dL adults
Familial
hyperchylomicronemia
Similar to familial
hypertriglyceridemia
Onset before
puberty indicates
deficiency of
lipoprotein lipase or
apo C-II, both
autosomal
recessive
Similar to familial
hypertriglyceridemia
CAD,coronaryarterydisease;GHIHBP1,glycosylphosphatidylinositol-anchoredhigh-density lipoprotein–bindingprotein1;
LDL,low-densitylipoprotein;VLDL,very-low-densitylipoprotein.
FHisanunderdiagnosed,autosomalco-dominantconditionwithaprevalenceofapproximately1
in200peoplethatcauseselevatedLDL-Clevelsfrombirth.
67,68
Itisassociatedwithsignificantly
increasedriskofearlyCVD.
69
Familial combined hyperlipidemia has a prevalence of 1%–2% and typically presents in
adulthood, although obesity and high dietary fat and sugar intake have led to increased
presentationinchildhoodandadolescence.
69
Standardsofcareforhyperlipidemia
LDL-C–lowering therapy, particularly with hydroxymethylglutaryl-coenzyme A (HMG-CoA)
reductase inhibitors (commonly referred to as statins), lowers the risk of CHD-related death,
morbidity, and revascularization procedures in patients with (secondary prevention) or without
(primaryprevention)knownCHD.
70-77
LDL-loweringtherapyhasprovenbeneficialeveninpatients
atlowriskforvasculardisease.
78
Prevention of ASCVD is the primary goal of the 2018 ACC/AHA guidelines. These guidelines
addressriskassessment,lifestylemodifications,evaluationandtreatmentofobesity,andevaluation
andmanagementofbloodcholesterolandaimforamorepersonalizedandshareddecision-making
approachtoriskmanagement.
79
Screening
Screeningforhypercholesterolemiashouldbedoneinalladultsage20yearsorolder.
79
Screening is best performed with a lipid profile (total cholesterol, LDL-C, HDL cholesterol, and
triglycerides)obtainedaftera12-hourfast.
If a fastinglipidpanelcannotbe obtained,totalandHDLcholesterolshouldbe measured.Non-HDL
cholesterol≥220mg/dLmayindicateageneticorsecondarycause.Afastinglipidpanelisrequiredif
non-HDLcholesterolis≥220mg/dLortriglyceridesare≥500mg/dL.
IfthepatientdoesnothaveanindicationforLDL-loweringtherapy,screeningcanbeperformedevery
4–6yearsbetweenages40and75.
79
Patientshospitalizedforanacutecoronarysyndromeorcoronaryrevascularizationshouldhavealipid
panelobtainedwithin24hoursofadmissioniflipidlevelsareunknown.
Individuals with hyperlipidemia should be evaluated for potential secondary causes, including
hypothyroidism,DM,obstructiveliverdisease,chronicrenaldiseasesuchasnephroticsyndrome,and
medicationssuchasestrogens,progestins,anabolicsteroids/androgens,corticosteroids,cyclosporine,
retinoids,atypicalantipsychotics,andantiretrovirals(particularlyproteaseinhibitors).
RiskAssessment
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The 2018 guidelines emphasize risk stratification based on predicted future risk, with further
stratificationusingrisk-enhancingfactorstoidentifygroupsinwhomthebenefitsofLDL-C–lowering
therapywithHMG-CoAreductaseinhibitors(statins)clearlyoutweightherisksandtoaimforcertain
goals in the reduction of LDL-C. The more LDL-C is reduced, the greater the subsequent risk
reduction.79Inallindividuals,ahearthealthylifestyleshouldbeencouragedasitreducesASCVDrisk
atallages.
Areasinwhichtreatmentwithstatintherapyisrecommendedincludethefollowing:
PatientswithclinicalASCVD
PatientswithLDL-C≥190mg/dL
PatientswithDMage40–75
Patientsage40–75withacalculatedASCVDrisk≥7.5%ifadiscussionoftreatmentoptionsfavors
statintherapy
For patients without clinical ASCVD or an LDL-C ≥190 mg/dL, the guidelines advise having a
clinician–patientriskdiscussionbeforestartingstatintherapy.Thisincludescalculatingapatient’srisk
for ASCVD based on age, sex, ethnicity, total and HDL cholesterol, SBP (treated or untreated),
presenceofDM,andcurrentsmokingstatusinadditiontothepresenceofrisk-enhancingfactors.
79
TheACC/AHAriskcalculatorisavailableattools.acc.org/ASCVD-Risk-Estimator-Plus/.
ForpatientsofethnicitiesotherthanAfricanAmericanornon-Hispanicwhite,riskcannot bewell
assessedwiththeriskcalculator.Useofthenon-Hispanicwhiteriskcalculationissuggested,with
the understanding that risk may be lower than calculated in East Asian Americans and Hispanic
AmericansandhigherinAmericanIndiansandSouthAsians.
Ten-yearriskshouldbecalculatedbeginningatage40inpatientswithoutASCVDorLDL-C≥190
mg/dL.
Lifetime riskmay be calculatedinpatients age20–39 and patients age40–59 witha 10-yearrisk
<7.5%toinformdecisionsregardinglifestylemodification.
TREATMENT
The2018guidelinesrecognizelifestylefactors,includingdietandweightmanagementasanimportant
componentofriskreductionforallpatients.
79
Patientsshouldbeadvisedtoadoptadietthatishighinfruitsandvegetables,wholegrains,fish,lean
meat,low-fatdairy,legumes,andnuts,withlowerintakeofredmeat,saturatedandtransfats,sweets,
and sugary beverages (Table 3-9). Saturated fat should comprise no more than 5%–6% of total
calories.
80
TABLE3-9
NUTRIENTCOMPOSITIONOFTHETHERAPEUTICLIFESTYLECHANGEDIET
54
Nutrient RecommendedIntake
Saturatedfat
a
<5%–6%oftotalcalories
Polyunsaturated
fat
Upto10%oftotalcalories
Monounsaturated
fat
Upto20%oftotalcalories
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Totalfat 25%–35%oftotalcalories
Carbohydrate
b
50%–60%oftotalcalories
Fiber 20–30g/d
Protein Approximately15%oftotalcalories
Cholesterol <200mg/d
Totalcalories
(energy)
c
Balanceenergyintakeandexpendituretomaintaindesirablebody
weight/preventweightgain
a
Transfattyacidsareanotherlow-densitylipoprotein–raisingfatthatshouldbekeptatalowintake.
b
Carbohydratesshouldbederivedpredominantlyfromfoodsrichincomplexcarbohydrates,includinggrains(especiallywhole
grains),fruits,andvegetables.
c
Dailyenergyexpenditureshouldincludeatleastmoderatephysicalactivity(contributingapproximately200kcal/d).
Effortsshouldbemadetoreplacedietarysaturatedfatwithpolyunsaturatedandmonounsaturatedfats,
asthishasbeenshowntolowerLDL-Candtriglycerides.Polyunsaturatedfatintakehasbeenshownto
promoteatherosclerosisregression.
81
Physicalactivity,includingaerobicandresistanceexercise,isrecommendedinallpatients.
70
The 2019 ACC/AHA guidelines recommend that adults engage in at least 150 minutes per week of
moderate-intensityor75minutesperweekofvigorous-intensityphysicalexercise.
82
Forallobesepatients(bodymassindex≥30)andforoverweightpatients(bodymassindex≥25)who
have additional risk factors, sustained weight loss of 5%–10% of initial weight, achieved through
lifestyle changes, has been shown to improve thelipid profile, lower BP, delaytheonset of type2
diabetes(T2DM),andimproveglycemiccontrolinthosewithT2DM.
82
Consultation with a registered dietitian nutritionist may be helpful to plan, start, and maintain a
saturatedfat–restrictedandweightloss–promotingdiet.
Priortothestartoftreatment,thereshouldbeariskdiscussionbetweenthepatientandtheclinician.
Topicsfordiscussionincludethefollowing:
PotentialforASCVDriskreductionbenefits
Potentialforadverseeffectsanddrug–druginteractions
Hearthealthylifestyleandmanagementofotherriskfactors
Patientpreferences
Aspirin should be used infrequently in the primary prevention of ASCVD because of lack of net
benefit.
82
Alladultsshouldbeassessedfortobaccouse.Thosewhosmokeshouldbestronglyadvisedtoquitand
providedassistanceinthispursuit.
82
ClinicalASCVD
Clinical ASCVD includes acute coronary syndromes, history of MI, stable angina, arterial
revascularization (coronary or otherwise), stroke, transient ischemic attack, or atherosclerotic
peripheralarterialdisease.
Secondary prevention is an indication for high-intensity statin therapy, which has been shown to
reduceeventsmorethanmoderate-intensity statintherapy. StatinregimensarelistedinTable3-10.
GoalisreductionofLDL-Cby>50%.
TABLE3-10
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STATINTHERAPYREGIMENSBYINTENSITY
53
HighIntensity(↓LDL
≥50%)
MediumIntensity(↓LDL30%–
49%)
LowIntensity(↓LDL
<30%)
Atorvastatin40–80mg Atorvastatin10–20mg Fluvastatin20–40mg
Rosuvastatin20–40mg Fluvastatin40mgbid,80mgXL
Lovastatin40mg
Pitavastatin1–4mg
Pravastatin40–80mg
Rosuvastatin5–10mg
Simvastatin20–40mg
Lovastatin20mg
Pravastatin10–20mg
Simvastatin10mg
LDL,low-densitylipoprotein;↓,decreased.
Ifhigh-dosestatintherapyiscontraindicated,poorlytolerated,ortherearesignificantriskstohigh-
intensitytherapy(includingage>75years),themaximallytoleratedstatintherapyisanoption.
In patients with very-high-risk ASCVD, use an LDL-C threshold of 70 mg/dL (1.8 mmol/L) to
consider addition of nonstatins to statin therapy. If proprotein convertase subtilisin/kexin type 9
(PCSK9)inhibitoris considered, add ezetimibetomaximalstatinbeforeaddingPCSK9inhibitor.
Very-high-riskASCVD includesa historyofmultiplemajor ASCVDeventsor onemajorASCVD
event andmultiplehigh-riskconditions(majorASCVDeventsarerecentacutecoronary syndrome
[past12months],historyofMI,historyofischemicstroke,symptomaticperipheralarterialdisease).
High-risk conditions include age >65 years, heterozygous FH, history of prior coronary bypass
surgery or percutaneous intervention outside the major ASCVD event, DM, hypertension, CKD
(eGFR15–59mL/min/1.73m2),currentsmoking,persistentlyelevatedLDL-C(>100mg/dL)despite
maximallytoleratedstatintherapyandezetimibe,historyofCHF.
InpatientswithT2DMandknownASCVD,considerstartinganSGLT2inhibitororGLP-1RAfor
cardiovascularandrenalbenefits.
82-84
LDL-C≥190mg/dL
These individuals have elevated lifetime riskbecause of long-term exposure to veryhigh LDL-C
levels,andtheriskcalculatordoesnotaccountforthis.
LDL-Cshouldbereducedwithhigh-intensitystatintherapy.Ifhigh-intensitytherapyisnottolerated,
maximumtoleratedintensityshouldbeused.
IfLDL-Constatintherapyremains>100mg/dL(>2.6mmol/L),addingezetimibeisreasonable.
IftheLDL-Clevelonstatinplusezetimiberemains>100mg/dL(>2.6mmol/L)andthepatienthas
multiple factors that increase subsequent risk of ASCVD event, a PCSK9 inhibitor may be
considered,althoughthelong-termsafety(>3years)isuncertain.
LDL apheresis is an optional therapy in patients with homozygous FH and those with severe
heterozygous FH with insufficient response to medication. Lomitapide, a microsomal triglyceride
transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide, are
medicationsindicatedforthetreatmentofpatientswithhomozygousFH.
66
Because hyperlipidemia ofthis degree is oftengeneticallydetermined,discuss screening ofother
familymembers(includingchildren)toidentifycandidatesfortreatment.Inaddition,screenforand
treatsecondarycausesofhyperlipidemia.
67
Patientswithdiabetes,aged40–75,LDL-C>70mg/dL
Moderate-intensitystatintherapyisindicatedregardlessofestimated10-yearASCVDrisk.
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InpatientswithDMathigherrisk,especiallythosewithmultipleriskfactorsorthoseaged50–75,it
isreasonabletouseahigh-intensitystatintoreducetheLDL-Cby>50%.
Diabetes-specific risk enhancers: long duration (>10 years for T2DM or >20 years for T1DM),
albuminuria(>30µgofalbumin/mgcreatinine),eGFR<60mL/min/1.73m2,retinopathy,neuropathy,
ankle-brachialindex(ABI)<0.9.
InadultswithDMand10-yearASCVDriskof20%orhigher,itmaybereasonabletoaddezetimibe
tomaximallytoleratedstatintherapytoreduceLDL-Cby50%ormore.
TheJACC2020ExpertConsensusDecisionPathwayonNovelTherapiesforCardiovascularRisk
ReductioninpatientswithT2DMrecommendsconsideringtheuseofansodium–glucose transport
protein2 (SGLT2) inhibitororglucagon-likepeptide-1receptor agonists(GLP-1 RA)for patients
with T2DM who are athigh risk for clinical ASCVD for cardiovascular andrenal benefits. The
2019 AHA/ACC preventative cardiology guidelines recommend metformin first-line and then
considerationofanSGLT2inhibitororGLP-1RAaswell.
82-84
Patientswithoutdiabetes,aged40–75,LDL-Cbetween70and189mg/dL
Using the AHA/ACC riskcalculator, calculate10-year risk of an ASCVD eventinthese patients
(categories:>20%,≥7.5%to<20%,5.0%–7.5%,and<5.0%).
“Borderlinerisk”:A10-yearriskbetween5.0%and7.5%andrisk-enhancingfactorsareindications
formoderate-intensitystatintherapyifadiscussionofoptionsfavorsstatintherapy.
“Intermediaterisk”:A10-yearrisk≥7.5%to<20%isanindicationformoderate-intensitystatinto
reduceLDL-Cby30%–49%.
“High risk”: A 10-year risk of >20% favors initiating statintherapy to reduceLDL-C by at least
50%.
82
Risk-enhancing factors include family historyof premature ASCVD, persistently elevated LDL-C
levels(>160mg/dL),metabolicsyndrome,CKD,historyofpreeclampsia or prematuremenopause
(<40years), chronicinflammatorydisorders(e.g.,rheumatoidarthritis, psoriasis,orchronicHIV),
high-riskethnicgroups(e.g.,SouthAsian),persistentelevationsoftriglycerides>175mg/dL,and,if
measuredinselectedindividuals,apolipoproteinB>130mg/dL,high-sensitivityC-reactiveprotein
>2.0mg/L,ABI<0.9,andLp(a)>50mg/dLor125nmol/L.
Inintermediate-riskadultsinwhomhigh-intensitystatinsareadvisabletoreachgoalreduction,but
not acceptable or tolerated, it is reasonable to add a nonstatin drug (ezetimibe or bile acid
sequestrant)tomoderate-intensitystatin.
Otherpatientpopulations
If a 10-yearASCVDriskis>7.5%–19.9%anddecisionaboutstatintherapyisuncertain,consider
measuringcoronaryarterycalcium(CAC)tohelpidentifyrisk.IftheCACiszero,itisreasonableto
withholdstatin therapyandreassessin5–10years,aslong as higherriskconditionsare absent.If
CACscoreis1–99,itisreasonabletoinitiatestatintherapyforpatients>55years.IfCACscoreis
>100and/orgreaterthan75thpercentile,itisreasonabletoinitiatestatintherapy.
Patients with stage3–5 CKDare high riskfor ASCVD85 andthe use of LDL-lowering therapy is
indicatedinpatientswithnondialysis-dependentCKD.
86
Useofstatin therapyshouldbeindividualizedforpatientsolderthan75.Inrandomizedcontrolled
trials,patientsolderthan75continuedtohavebenefitfromstatintherapy,particularlyforsecondary
prevention.
73,87
Inaddition,manyASCVDeventsoccurinthisagegroup,andpatientswithoutother
comorbiditiesmaybenefitsubstantiallyfromcardiovascularriskreduction.
Inadults>75yearsitmaybereasonabletostopstatintherapywhenfunctionaldecline(physicalor
cognitive), multimorbidity,frailty, or reduced lifeexpectancylimits thepotential benefitsofstatin
therapy.
In adultswithadvancedkidneydiseasethatrequiresdialysistreatmentwhoarecurrentlyonLDL-
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