ANNALS Dyslipidemia

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Dyslipidemia

Prevention and Screening page ITC2-2

Diagnosis page ITC2-4

Treatment page ITC2-7

Practice Improvement page ITC2-13

CME Questions page ITC2-16

Section EditorsBarbara Turner, MD, MSEDSankey Williams, MDDarren Taichman, MD, PhD

Physician WritersLaurie Kopin, MS, ANPCharles Lowenstein, MD

The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), includingPIER (Physicians’ Information and Education Resource) and MKSAP (MedicalKnowledge and Self-Assessment Program). Annals of Internal Medicineeditors develop In the Clinic from these primary sources in collaborationwith the ACP’s Medical Education and Publishing Division and with the assistance of science writers and physician writers. Editorial consultants fromPIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consulthttp://pier.acponline.org, http://www.acponline.org/products_services/mksap/15/?pr31, and other resources referenced in each issue of In the Clinic.

CME Objective: To review current evidence for the prevention and screening,diagnosis, and treatment of dyslipidemia.

The information contained herein should never be used as a substitute for clinical judgment.

© 2010 American College of Physicians

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What preventive lifestylemeasures should cliniciansrecommend to reduce risk fordyslipidemia?Lifestyle changes can favorably af-fect total cholesterol, HDL choles-terol, LDL cholesterol, and triglyc-eride levels. The American HeartAssociation (AHA) recommendsthat all adults consume a healthydiet, exercise regularly, and avoidtobacco smoke. However, the U.S.Preventive Services Task Force(USPSTF) points out that lifestylemodifications, such as diet andphysical activity, are unlikely tosubstantially reduce lipid levels andthat many patients with hyperlipi-demia require drugs to reach thera-peutic goals (4, 5).

Regardless of the presence of pre-existing CHD, patients who adoptthese habits will have healthier lipidprofiles, reducing their CHD risk.Because of their higher baseline risk,patients with CHD or coronary ar-tery disease (CAD) risk–equivalentconditions (Box) may see the mostmarked reduction in risk for poorhealth outcomes. Ultimately, in-creasing healthy lifestyles should reduce population-wide lipid levelsand, consequently, reduce the needfor drug therapy.

Who should be screened fordyslipidemia?No direct evidence links lipidscreening and subsequent treatmentwith reduced adverse outcomes

from CVD or stroke. However,moderate-quality indirect evidencesupports routine dyslipidemiascreening for men older than 35years and women older than 45years (6). According to the USPSTF, clinicians should alsoscreen younger adults (men aged 20to 35 years or women aged 20 to45 years) who have other risk fac-tors for CVD, whose family historyof premature CHD or history oflipid abnormalities suggests a heri-table familial lipid disorder, or whohave evidence of hyperlipidemia onphysical examination. In contrast,the National Cholesterol EducationProgram Adult Treatment Panel III(NCEP-ATP III) recommends be-ginning screening of all adults atage 20 years, regardless of theirCHD risk profile (5). This recom-mendation is based on the rationalethat screening promotes healthybehaviors, increases public aware-ness of cholesterol, and identifiespatients with a high risk for CHD(7, 8). However, the incrementalyield and cost-effectiveness of earli-er universal screening versus riskfactor–based screening in youngadults is unclear.

In 2007, the USPSTF concludedthat the evidence was insufficientto recommend for or against rou-tine screening for lipid disorders inchildren or adolescents (aged ≤20years) (9). But, in 2010, the USPSTF recommended routinescreening for overweight and

© 2010 American College of Physicians ITC2-2 In the Clinic Annals of Internal Medicine 3 August 2010

1. Centers for DiseaseControl and Preven-tion. Cholesterol. Ac-cessed atwww.cdc.gov/nchs/fastats/cholest.htm on22 June 2010.

2. Anderson KM, CastelliWP, Levy D. Choles-terol and mortality.30 years of follow-upfrom the Framing-ham study. JAMA.1987;257:2176-80.[PMID: 3560398]

3. Goldbourt U, Yaari S.Cholesterol and coro-nary heart diseasemortality. A 23-yearfollow-up study of9902 men in Israel.Arteriosclerosis.1990;10:512-9.[PMID: 2369362]

4. Grundy SM, BaladyGJ, Criqui MH, et al.Guide to primary pre-vention of cardiovas-cular diseases. Astatement for health-care professionalsfrom the Task Forceon Risk Reduction.American Heart Asso-ciation Science Advi-sory and Coordinat-ing Committee.Circulation.1997;95:2329-31.[PMID: 9142014]

More than 15% of U.S. adults have high serum cholesterol levels. Hy-percholesterolemia is a major risk factor for cardiovascular disease(CVD), cardiovascular death, and all-cause mortality (1). Large ob-

servational studies have reported a strong, graded relationship between increas-ing levels of low-density lipoprotein (LDL) cholesterol or decreasing levels ofhigh-density lipoprotein (HDL) cholesterol and increasing risk for atheroscle-rotic coronary heart disease (CHD) events (2, 3). Long-term, prospective epi-demiologic studies have consistently shown that persons with healthier lifestylesand fewer CHD risk factors, and particularly persons with favorable lipid pro-files, have lower incidences of CHD. Prevention and sensible management ofdyslipidemia can markedly alter cardiovascular morbidity and mortality.

Prevention and

Screening

Coronary Artery DiseaseEquivalents• Diabetes mellitus• Aortic aneurysm• Peripheral vascular disease

(claudication, ankle–brachialindex <0.9)

• Symptomatic carotid artery disease(transient ischemic attack, stroke)

• 10-year risk for coronary arterydisease >20% using Framinghamrisk equation


© 2010 American College of PhysiciansITC2-3In the ClinicAnnals of Internal Medicine3 August 2010

obesity in persons younger than 20years (10). The American Associa-tion of Pediatrics (AAP) recom-mends a more aggressive screeningpolicy: targeted screening of chil-dren and adolescents aged 2 yearsor older for abnormal blood lipidlevels based on family history andother CVD-related risk factors(11). Untreated abnormal lipid lev-els in children and adolescents arelinked to increased risk for CHDin adulthood, so behavioral lifestylecounseling is an important first stepto prevent or reduce abnormal lipidlevels in youths (10). This lifestylecounseling is particularly importantfor young persons with 1 or moreCVD risk factors and high LDLcholesterol levels or who are over-weight or obese with low HDLcholesterol levels or high triglyc-eride levels. The AAP recommendsconsidering pharmacologic inter-vention to treat children whoseLDL cholesterol level remains per-sistently high even after therapeuticlifestyle counseling (10).

Moderate-quality evidence supportsscreening adults older than 65 years.Total cholesterol level predictsCHD in elderly persons. Personsolder than 65 years have a higherbaseline risk for CHD, increasingtheir potential absolute benefit frominterventions to manage dyslipi-demia (12). Regardless of age, allpatients with known CHD or CADrisk equivalent conditions shouldhave lipid levels measured.

How and how often shouldclinicians screen for dyslipidemia?The AHA and the NationalCholesterol Education Program(NCEP) recommends that everyadult age 20 years or older havetheir fasting lipid profile meas-ured every 5 years (4, 5). Howev-er, the USPSTF recommenda-tions are more restrictive thanthose of the AHA and NCEP.The USPSTF recommends lipidscreening for men older than 35years and women older than 45

years who have an increased riskfor CHD. Furthermore, theUSPSTF recommends measure-ment of only total cholesterol andHDL cholesterol instead of acomplete lipid profile and acceptslipid profiles from both fastingand nonfasting subjects (6).A study of fasting versus nonfasting totalcholesterol values in 181 general internalmedicine outpatients found no clinicallyimportant differences between fasting andnonfasting results for total and HDL cho-lesterol levels (13). Another large cross-sectional population study that comparedfasting and non-fasting lipid profiles for 33 391 persons aged 20 to 95 years report-ed that lipid profiles changed minimally inresponse to normal food intake in personsin the general population (14).

The NCEP-ATP III advocates ini-tial screening with a fasting lipidprofile that includes measurementof triglycerides and indirect calcula-tion of LDL cholesterol level (5).The USPSTF does not recommendtriglyceride measurement as part ofa lipid profile evaluation (6). Meas-urements of LDL cholesterol andtriglyceride levels are useful forguiding treatment, but do not im-prove on risk prediction as with to-tal and HDL cholesterol values.

The primary treatment target isLDL cholesterol level. Once theLDL cholesterol goal has been at-tained, attention should turn toother lipid risk factors when pres-ent. If triglycerides are high (≥2.26mmol/L [≥200 mg/dL]), the sec-ondary target of treatment be-comes non-HDL cholesterol level.Non–HDL cholesterol level is thedifference between the total andHDL cholesterol levels and in-cludes the cholesterol carried on allof the potentially proatherogenicapolipoprotein B–containing parti-cles, such as very low-densitylipoprotein (VLDL) cholesterol,intermediate-density lipoproteincholesterol, and LDL cholesterolas well as chylomicrons (triglyc-eride-rich) and lipo protein(a). If

5. National CholesterolEducation Program.Detection, Evaluation,and Treatment ofHigh Blood Choles-terol in Adults.Bethesda, MD: Na-tional Institutes ofHealth; 2002. Ac-cessed atwww.nhlbi.nih.gov/guidelines/choles-terol/atp3full.pdf on22 June 2010.

6. U.S. Preventive Servic-es Task Force. Screen-ing for Lipid Disor-ders in Adults.Rockville, MD: U.S.Department ofHealth and HumanServices; 2001. Ac-cessed atwww.ahrq.gov/clin-ic/uspstf/uspschol.htm on 22 June 2010.

7. Cleeman JI, GrundySM. National Choles-terol Education Pro-gram recommenda-tions for cholesteroltesting in youngadults. A science-based approach. Cir-culation.1997;95:1646-50.[PMID: 9118536]

8. LaRosa JC, He J, Vup-puturi S. Effect ofstatins on risk ofcoronary disease: ameta-analysis of ran-domized controlledtrials. JAMA.1999;282:2340-6.[PMID: 10612322]

9. U.S. Preventive Servic-es Task Force. Screen-ing for lipid disordersin children. Rockville,MD: U.S. Departmentof Health and HumanServices; 2007. Ac-cessed atwww.ahrq.gov/clin-ic/uspstf/uspschlip.htm on 22 June 2010.

10. Barton M; US Pre-ventive Services TaskForce. Screening forobesity in childrenand adolescents: USpreventive servicestask force recom-mendation state-ment. Pediatrics.2010;125:361-7.[PMID: 20083515]

11. Daniels SR, Greer FR;Committee on Nutri-tion. Lipid screeningand cardiovascularhealth in childhood.Pediatrics.2008;122:198-208.[PMID: 18596007].

12. Murray DM, Kurth C,Mullis R, et al. Cho-lesterol reductionthrough low-intensi-ty interventions: re-sults from the Min-nesota Heart HealthProgram. Prev Med.1990;19:181-9.[PMID: 259741]


13. Craig SR, Amin RV,Russell DW, et al.Blood cholesterolscreening influenceof fasting state oncholesterol resultsand managementdecisions. J Gen In-tern Med.2000;15:395-9.[PMID: 10886474]

14. Langsted A, FreibergJJ, Nordestgaard BG.Fasting and nonfast-ing lipid levels: influ-ence of normal foodintake on lipids,lipoproteins,apolipoproteins, andcardiovascular riskprediction. Circula-tion. 2008;118:2047-56. [PMID: 18955664]

15. Grover SA, Coupal L,Hu XP. Identifyingadults at increasedrisk of coronary dis-ease. How well dothe current choles-terol guidelineswork? JAMA.1995;274:801-6.[PMID: 7650803]


the LDL cholesterol goal has beenattained but the non-HDL choles-terol goal has not, there are 2 alter-native approaches: Increase thedose of the LDL-lowering drug toreduce both LDL and VLDL cho-lesterol levels, or consider adding atriglyceride-lowering drug (fibrateor nicotinic acid) to LDL choles-terol–lowering therapy, which willmainly lower VLDL cholesterollevels. Thereafter, persons can bemonitored for response to therapyevery 4 or 6 months, or more oftenif considered necessary (5). Calcu-lation of LDL cholesterol level isbest performed on a lipid profileobtained after the patient has fast-ed for at least 8 to 10 hours. Direct

measurement of LDL cholesterollevel does not require the patientto be fasting, but it may be expen-sive and does not improve on riskprediction. However, direct meas-urement is necessary when triglyc-eride levels are greater than 4.52 mmol/L (>400 mg/dL).

In the absence of data to support aspecific screening interval, screeningevery 5 years seems to be reasonablein low-risk patients, because lipidlevels do not vary greatly from year toyear. Clinicians might consider morefrequent screening for patients whohave lipid values near treatmentthresholds or who develop new car-diovascular risk factors.

An electronic tool for calculatingrisk is publicly available at a Na-tional Heart Lung and Blood Dis-ease Web site (http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof ) (16). The Fram-ingham risk equation allows theclinician to classify patients by theirlevel of risk: CHD or CAD riskequivalent (Box) (including >20%10-year risk for a cardiovascularevent), moderate risk (10% to 20%risk), or low risk (<10%). These as-sessments of risk should guidetreatment strategies and goals.

What laboratory test resultsshould clinicians obtain beforestarting therapy for dyslipidemia?High levels of LDL cholesterol inpersons with 2 or more CAD risk

How should clinicians interpretresults of lipid screening inrelation to evaluating overallcardiovascular risk?When diagnosing dyslipidemia, cli-nicians should estimate a patient’scardiovascular risk. Calculation ofrisk using specific risk equationsseems to be more accurate than using lipid levels alone or simplycounting risk factors.

Data from the Lipid Research ClinicPrevalence and Follow-up Studies, whichincluded 3678 men and women aged 35to 74 years, suggest that a Framingham-based coronary risk model (area underthe receiver-operating characteristiccurve, 0.85) was superior to all otherforms of risk assessment, including lipidmeasures alone and algorithms basedon expert guidelines (15).

Prevention and Screening... Healthy diet, regular exercise, and avoidance of tobaccocan help patients avoid or reduce dyslipidemia. Evidence supports routine screeningfor dyslipidemia in men aged 35 years or older and women aged 45 years or older.However, the NCEP-ATP III advocates that screening for dyslipidemia begin at age 20 years, in part, to increase awareness of dyslipidemia and promote healthy behav-iors. Screening at earlier ages is warranted for children and adolescents with cardio-vascular risk factors or a clinical history suggestive of familial hyperlipidemia. Although authorities disagree on which cholesterol values to measure and at whatage to begin testing, AHA and NCEP guidelines recommend measuring a fasting lipidprofile on all adults age 20 years or older every 5 years (5).

CLINICAL BOTTOM LINE

Diagnosis


16. National CholesterolEducation Program.Risk Assessment Toolfor Estimating 10-year Risk of Develop-ing Hard CHD (My-ocardial Infarctionand CoronaryDeath). Bethesda,MD: National Insti-tutes of Health; 2002Accessed athttp://hp2010.nhlbi-hin.net/atpiii/calcu-lator.asp?usertype=prof 22 June 2010.

17. Brand FN, Larson M,Friedman LM, et al.Epidemiologic as-sessment of anginabefore and after my-ocardial infarction:The Framinghamstudy. Am Heart J.1996;132:174-8.[PMID: 8701860]

18. Martineau P, Gaw A,de Teresa E, et al;ACTFAST investiga-tors. Effect of indi-vidualizing startingdoses of a statin ac-cording to baselineLDL-cholesterol lev-els on achievingcholesterol targets:the achieve choles-terol targets fastwith atorvastatinstratified titration(ACTFAST) study.Atherosclerosis.2007;191:135-46.[PMID: 16643923]

19. Miller M. Is hyper-triglyceridaemia anindependent riskfactor for coronaryheart disease? Theepidemiological evi-dence. Eur Heart J.1998;19 SupplH:H18-22.[PMID: 9717060]

20. Sarwar N, Danesh J,Eiriksdottir G, et al.Triglycerides and therisk of coronaryheart disease: 10,158incident casesamong 262,525 par-ticipants in 29 West-ern prospectivestudies. Circulation.2007;115:450-8.[PMID: 17190864]

21. Austin MA, Hokan-son JE, Edwards KL.Hypertriglyc-eridemia as a cardio-vascular risk factor.Am J Cardiol.1998;81:7B-12B.[PMID: 9526807]

22. The Lipid ResearchClinics Coronary Pri-mary Prevention Trialresults. I. Reductionin incidence of coro-nary heart disease.JAMA. 1984;251:351-64. [PMID: 6361299]


factors have been associated inprospective studies with an absolute10-year risk of more than 20% formyocardial infarction or CADdeath (17). Furthermore, clinicaltrials show that therapy targeted atreducing LDL cholesterol levelsdecreases the risk for CHD death.Therefore, the clinician must firstfocus on identifying and treatingelevated LDL cholesterol levels.

Before initiating potentially life-long therapy, clinicians need torisk-stratify patients and set appro-priate LDL cholesterol goals. It isimportant to identify causes of ele-vated LDL cholesterol levels to appropriately target diet and drugtherapy. The efficacy in loweringLDL cholesterol level depends onhow high it is at baseline (18).

How should clinicians measureand interpret triglyceride and HDLcholesterol levels?Triglyceride levelsTriglyceride levels are a secondarytarget for therapy. Numerousprospective epidemiologic studieshave shown that increased triglyc-eride levels are related to increasedrisk for CAD (19), and a meta-analysis of prospective studiesshows that high triglyceride levelsare an independent risk factor forCAD (20).

The association of elevated triglyc-eride levels with CAD seems to bestronger for women than men (20),because, in men, adjustment forother risk factors (for example, dia-betes, HDL cholesterol level, obe-sity) seems to explain this associa-tion (21). The clinician shouldstratify patients based on fastingtriglyceride levels as follows: nor-mal, less than 1.70 mmol/L (<150 mg/dL); borderline high,1.70 to 2.25 mmol/L (150 to 199mg/dL); high, 2.26 to 5.64mmol/L (200 to 499 mg/dL); andvery high, greater than 5.65mmol/L (>500 mg/dL). Borderlinehigh triglyceride levels suggest

specific familial abnormalities oftriglyceride-rich lipoprotein metabo-lism in which the liver overproducestriglyceride-rich lipoproteins. In per-sons with high triglyceride levels(>2.26 mmol/L [>200 mg/dL]), theAdult Treatment Panel (ATP) IIIsuggests that non-HDL cholesterolis a secondary target for lipid-lowering therapies (5). However, it isimportant to note that LDL choles-terol level is the primary target for allpatients with hyperlipidemia.

Persons with elevated triglyceridelevels are more likely to have themetabolic syndrome. High triglyc-eride levels may also result from re-duced clearance of triglyceride-richlipoproteins or may identify per-sons with other clinical problemsthat require intervention (for exam-ple, diabetes, alcoholism, chronicrenal failure, and the nephrotic syn-drome). Triglyceride levels greaterthan 5.65 mmol/L (>500 mg/dL)are associated with pancreatitis andwarrant treatment.

HDL cholesterol levelHDL cholesterol levels are 1 of 5factors used in Framingham riskscoring and are inversely associatedwith CHD. Coronary events de-crease 2% for every 1% increase inHDL cholesterol level (22). AnHDL cholesterol level greater than1.6 mmol/L (>60 mg/dL) has beenassociated with a decreased risk forcoronary events, whereas an HDLcholesterol level less than 1.0mmol/L (<40 mg/dL) predicts anincrease in coronary events. LowHDL cholesterol levels are causedmost commonly by acquired condi-tions, such as smoking tobacco,obesity, inactivity, hypertriglyc-eridemia, type 2 diabetes mellitus,and a high-carbohydrate diet. LowHDL cholesterol levels can also becaused by drugs, such as β-blockersor androgenic steroids. Genetic ab-normalities, including mutations ingenes encoding apoA-I, LCAT, andABC1, can also decrease HDLcholesterol levels.


23 Gordon T, Castelli WP,Hjortland MC, Kan-nel WB, Dawber TR.High densitylipoprotein as a pro-tective factor againstcoronary heart dis-ease. The Framing-ham Study. Am JMed. 1977;62:707-14. [PMID: 193398]

24. Stone N, Blum C.Management ofLipids in ClinicalPractice. Caddo, OK:Professional Com-munications; 2010.

25. Ernst ND, SemposCT, Briefel RR, et al.Consistency be-tween US dietary fatintake and serum to-tal cholesterol con-centrations: the Na-tional Health andNutrition Examina-tion Surveys. Am JClin Nutr.1997;66:965S-972S.[PMID: 9322575]


Before initiating drug therapy in apatient with an HDL cholesterollevel less than 1.0 mmol/L (<40 mg/dL), it is important to ruleout other possible contributing fac-tors, such as smoking tobacco; somemedications (Box); and lifestylehabits, such as being sedentary.When patients have CHD or anequivalent condition and an HDLcholesterol level less than 1.0mmol/L (<40 mg/dL), they shouldreceive nicotinic acid or fibrate ther-apy (23); however, better-toleratedand more effective therapeuticagents are in development (19).

What should clinicians look for inthe history and physicalexamination of a patient withdyslipidemia?History and physical examinationshould focus on identifying coronaryrisk factors and detecting secondarycauses of dyslipidemia. A thoroughhealth history, including a detailedreconciliation of all medications,should be performed, because some medications may affect lipidlevels, such as thiazide diuretics, β-blockers, anabolic steroids, and estrogens/progestins (Box). TheFramingham Risk Calculationshould be performed to risk-stratifythe patient (16). The physical exam-ination should include measuringthe body mass index (BMI), check-ing the blood pressure, and examin-ing peripheral pulses as well aschecking carotids and other vesselsfor bruits. An examination of theliver and thyroid may also identifysecondary causes of dyslipidemia.

What are the causes of secondarydyslipidemia, and how shouldclinicians diagnose them?Secondary causes of dyslipidemiainclude hypothyroidism, obstruc-tive liver disease, the nephroticsyndrome, renal failure, uncon-trolled diabetes mellitus, and tobacco or alcohol use. The clini-cian should review the patient’smedications for those that cancause dyslipidemia (Box).

It is important to address second-ary causes before starting drugtherapy to reduce lipids, becausethe abnormality may resolve afteraddressing these factors and be-cause drug therapy may be inef-fective in persons with these conditions. If a drug is suspectedas the cause of the lipid abnor-mality, consider the benefits ver-sus the risks before discontinuingtherapy.

When should clinicians considerspecialized lipid tests or referralto a specialist?Clinicians should consider anapolipoprotein evaluation and re-ferral to a lipid specialist whenthey suspect the patient has a ge-netic familial hypercholes-terolemia. Apolipoproteins areproteins in lipid particles, andtheir measurement can be helpfulfor 2 reasons. First, direct meas-urement of apolipoproteins can bemore accurate than measurementof lipid levels in the setting ofmassively elevated lipids. Second,measurement of apolipoproteinscan provide clues about the causeof some dyslipidemias. An assess-ment of particle size may be war-ranted in these patients, alongwith levels of apolipoprotein Aand B to provide a more detailedcharacterization of the given lipiddisorder. Accurate typing can helpguide the choice of therapeuticpharmacologic agents. When agenetic disorder of lipid metabo-lism is suspected, especially inconjunction with a history of pre-mature atherosclerotic disease, alipoprotein(a) level can serve as a

Drugs That Can Cause Dyslipidemia• Corticosteroids• Androgenic steroids• Progestogens• Thiazide diuretics• β-blockers• Retinoic acid derivatives• Oral estrogens


26. de Lorgeril M, SalenP, Martin JL, et al.Mediterranean diet,traditional risk fac-tors, and the rate ofcardiovascular com-plications after my-ocardial infarction: fi-nal report of theLyon Diet HeartStudy. Circulation.1999;99:779-85.[PMID: 9989963]

27. Carleton RA, Baz-zarre T, Drake J, et al.Report of the ExpertPanel on Awarenessand BehaviorChange to the Boardof Directors, Ameri-can Heart Associa-tion. Circulation.1996;93:1768-72.[PMID: 8653885]


risk marker for futureatherothrombotic events (24).Screening first-degree relativesshould be strongly considered. It

can be very difficult to controllipid levels in these patients, andthey have an increased risk forearly CHD.

TreatmentOverweight patients (BMI, 25 to29.9 kg/m2) and obese patients(BMI, >30 kg/m2), should reducetheir caloric intake from fats andsimple carbohydrates and aim for atleast 30 minutes of physical activityon most days. A structured aerobicexercise program using large-musclegroups (for example, running, walk-ing, cycling, or swimming) willgreatly enhance weight reductionprograms. Studies of weight losswith or without exercise suggestthat exercise facilitates achievingoptimum lipid levels (27).

The clinician and patient shouldset goals and select treatmentstrategies for weight loss and riskfactor control and should scheduleperiodic weight checks and mainte-nance counseling. Obese patientsmay require more intensive inter-ventions and counseling for weightreduction.

When should cliniciansrecommend drug therapy?Decisions about adding drug thera-py to dietary modifications dependon underlying risk factors and onthe patient’s clinical situation.Strong evidence supports drugtherapy for high-risk patients whenLDL cholesterol levels exceedNCEP-ATP III goals (Box). In

What should clinicians advisepatients with dyslipidemia aboutlifestyle changes?All patients with lipid disordersshould be advised about the impor-tance of behavioral lifestylechanges. Patients should adoptthese changes regardless of whetheror not drug therapy is being pre-scribed. Use of the NCEP-ATP IIITherapeutic Lifestyle Change Dietcan result in a 5% to 15% reductionin LDL cholesterol level. Accord-ing to the National Health andNutrition Examination Survey(NHANES) III, a 15% reductionin LDL cholesterol can reduce theneed for cholesterol-lowering drugsfrom 14% to 5% of the population,if adopted by everyone (25). A dietrich in fruits, vegetables, nuts, andwhole grains with use of mono-unsaturated oils (for example, oliveoil and canola oil) and low in redmeat and animal fat seems to sub-stantially reduce risk, independentof serum lipid levels (26). Increasedsoy consumption can increaseHDL cholesterol level.

Patients with dyslipidemia and anormal BMI of 18.5 to 24.9 kg/m2

should focus on healthy eating andregular exercise in order to main-tain a normal body weight and reduce their lipid levels (4).

Diagnosis... Low-density lipoprotein cholesterol levels should be interpreted inlight of cardiovascular risk based on the Framingham risk equation. Measure-ment of high-density lipoprotein cholesterol and triglyceride levels can helpidentify the causes of dyslipidemia and further target interventions. Historyand physical examination should focus on the identification of coronary heartdisease, cardiovascular risk factors, and potential secondary causes of dyslipi-demia. Specialized testing and specialty referral may be useful when familialhypercholesterolemia is suspected.



28. Grundy SM, Paster-nak R, Greenland P,et al. V. Assessmentof cardiovascular riskby use of multiple-risk-factor assess-ment equations: astatement forhealthcare profes-sionals from theAmerican Heart As-sociation and theAmerican College ofCardiology. Circula-tion. 1999;100:1481-92. [PMID: 10500053]


patients with none or 1 CHD riskfactor, a 6-month trial of lifestylechanges should be completed be-fore initiating treatment. WhenLDL cholesterol levels are morethan 15% above threshold, startingdrugs earlier may be reasonable. Inpatients with CAD or a CADequivalent, an LDL cholesterol lev-el greater than 2.59 mmol/L (>100mg/dL) should prompt initiation ofdrug therapy. In high-risk patientswho show CVD progression, someclinicians begin therapy at lowerLDL cholesterol levels (that is,>1.8 mmol/L [>70 mg/dL]). In pa-tients who are hospitalized with acardiovascular event, even though

Implementation of Interventions forDyslipidemia Based on NCEP-ATP IIIGoals

Patients with none or 1 cardiac riskfactor• LDL cholesterol level ≥4.14 mmol/L

(≥160 mg/dL), institute lifestylechanges.

• LDL cholesterol level ≥4.9 mmol/L(≥190 mg/dL), add drug therapy.

• LDL cholesterol 4.14 to 4.89 mmol/L(160 to 189 mg/dL), consider addingdrug therapy based on patientpreferences.

Patients with 2 or more risk factorsand 10-year risk <10%• LDL cholesterol level ≥3.35 mmol/L

(≥130 mg/dL), institute lifestylechanges.

• LDL cholesterol level ≥4.14 mmol/L(≥160 mg/dL), consider adding drugtherapy.

Patients with 10-year risk 10% to20%• LDL cholesterol level ≥3.35 mmol/L

(≥130 mg/dL), strongly consideradding drug therapy to lifestylechanges.

• LDL cholesterol level 2.59 to 3.34mmol/L (100 to 129 mg/dL), consideradding drug therapy to lifestylechanges based on patient preferences.

Patients with 10-year risk >20%, CAD,or CAD risk equivalent• LDL cholesterol level ≥2.59 mmol/L

(≥100 mg/dL), initiate drug therapyand lifestyle changes.

• LDL cholesterol level 1.81 to 2.59mmol/L (70 to 100 mg/dL), initiatelifestyle changes and consider drugtherapy.

cholesterol levels can change duringhospitalization, LDL cholesterol-lowering drugs should be initiatedbefore discharge when the LDLcholesterol level is 3.35 mmol orgreater (≥130 mg/dL). Clinicaljudgment should be used when thecholesterol level is 2.59 to 3.34mmol/L (100 to 129 mg/dL) (28).Reduction in LDL cholesterol lev-els will reduce the risk for clinicalcoronary disease and stroke in di-verse situations, including primaryprevention, secondary prevention,and persons with diabetes. The rec-ommendations about when to starttherapy are based on the data sup-porting the effectiveness of drugtherapy for reducing cardiovascularevents by improving lipid levels.

What options are available fordrug therapy?There are various lipid-loweringagents to use alone or in combina-tion to achieve NCEP-ATP IIIcholesterol goals (Table 1). Astrong knowledge of drug actionsand interactions allows the clinicianto adapt drug therapy to meet thespecific lipid abnormality. AfterLDL cholesterol goals are attained,reduce triglyceride levels to lessthan 1.7 mmol/L (<150 mg/dL)and then attempt to increase HDLcholesterol levels to greater than1.0 mmol/L (>40 mg/dL) by selec-tion or combination of drugs witheffects on multiple lipoproteins.The selection of the agent dependson the type of dyslipidemia (Box).

When is combination drug therapy for dyslipidemiawarranted?Combination therapy should beconsidered in patients with severe-ly elevated lipid levels that are un-responsive to monotherapy. Insome disorders, such as familialhypercholesterolemia, up to 3 or 4drugs may be required. Many randomized trials of short dura-tion (3 to 6 months) have com-pared single and combination drugregimens for their effects on serum



Selection of Drugs for Lipid Control• For high LDL cholesterol level only, consider statins first, resins or an intestinal absorption-

blocker second, and niacin third.• For high LDL cholesterol and low HDL cholesterol levels, consider statins first and niacin

second.• For high LDL cholesterol, low HDL cholesterol, and high triglyceride levels, consider niacin

and statins first and fibrates second.• For high triglyceride levels, with or without low HDL cholesterol levels, consider fibrates

first and niacin second.• For low HDL cholesterol levels only, consider niacin first and fibrates second.

Table 1. Goals for Therapy Using LDL Cholesterol LevelsRisk Group LDL Cholesterol Initiate Therapeutic Consider

Goal Lifestyle Changes Drug Therapy

mmol/L mg/dL mmol/L mg/dL mmol/L mg/dL

High riskCHD or CHD risk <2.59 <100 ≥2.59 ≥100† ≥2.59 ≥100

equivalents (optional (optional (consider (10-year risk goal goal drug >20%)* <1.81) <70) options

if <100)‡

Moderately high risk≥2 risk factors§ <3.35 <130 ≥3.35 ≥130† ≥3.35 ≥130

(10-year risk (optional (optional (consider 10% to 20%) goal goal drug

<2.59) <100) options if 100 to 129)||

Moderate risk≥2 risk factors§ <3.35 <130 ≥3.35 ≥130 ≥4.14 ≥160

(10-year risk <10%)

Lower risk0 to 1 risk factor <4.14 <160 ≥4.14 ≥160 ≥4.92 ≥190 (LDL

cholesterol–lowering drug

optional if 160 to 189)

CHD = coronary heart disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein.

* CHD includes history of myocardial infarction, unstable angina, stable angina, coronary artery proce-dures (angioplasty or bypass surgery), or evidence of clinically significant myocardial ischemia. CHDrisk equivalents include clinical manifestations of noncoronary forms of atherosclerosis (peripheralvascular disease, abdominal aortic aneurysm, carotid disease, and stroke; diabetes, and ≥2 risk factorswith 10-year risk for CHD >20%).

† Any person at high risk or moderately high risk who has lifestyle-related risk factors (obesity, physi-cal inactivity, elevated triglyceride levels, low HDL cholesterol levels, or the metabolic syndrome) is acandidate for therapeutic lifestyle changes to modify these risk factors regardless of LDL cholesterollevels.

‡ If baseline LDL cholesterol level is <2.59 mmol/L (<100 mg/dL), an LDL cholesterol–lowering drug is atherapeutic option on the basis of available clinical trial results. If a high-risk person has high triglyc-eride levels and low HDL cholesterol levels, combining a fibrate or nicotinic acid with an LDL choles-terol–lowering drug can be considered.§ Risk factors include cigarette smoking, hypertension (blood pressure ≥140/90 mm Hg or on medica-tion), low HDL cholesterol level (<1.03 mmol/L [<40 mg/dL]), family history of premature CHD (<55years of first-degree male relative and <65 years of first-degree female relative), and age (men, ≥45years; women, ≥55 years).

|| For moderately high-risk persons, when LDL cholesterol levels are 2.59 to 3.34 mmol/L (100 to 129mg/dL), at baseline or with lifestyle therapy, using an LDL cholesterol–lowering drug to achieve an LDLcholesterol level <2.59 mmol/L (<100 mg/dL) is a therapeutic option on the basis of available clinicaltrial results.


29. Ezetimibe StudyGroup. Effect of eze-timibe coadminis-tered with atorvas-tatin in 628 patientswith primary hyperc-holesterolemia: aprospective, ran-domized, double-blind trial. Circula-tion.2003;107:2409-15.[PMID: 12719279]

30. Ezetimibe StudyGroup. Efficacy andsafety of ezetimibeadded to ongoingstatin therapy fortreatment of pa-tients with primaryhypercholes-terolemia. Am J Car-diol. 2002;90:1084-91. [PMID: 12423708]

31. Pearson TA, DenkeMA, McBride PE, etal. A community-based, randomizedtrial of ezetimibeadded to statin ther-apy to attain NCEPATP III goals for LDLcholesterol in hyper-cholesterolemic pa-tients: the ezetimibeadd-on to statin foreffectiveness (EASE)trial. Mayo Clin Proc.2005;80:587-95.[PMID: 15887425]

32. Rossebø AB, Peder-sen TR, Boman K, etal; SEAS Investiga-tors. Intensive lipidlowering with sim-vastatin and ezetim-ibe in aortic stenosis.N Engl J Med.2008;359:1343-56.[PMID: 18765433]

33. Kastelein JJ, Akdim F,Stroes ES, et al; EN-HANCE Investigators.Simvastatin with orwithout ezetimibe infamilial hypercholes-terolemia. N Engl JMed. 2008;358:1431-43. [PMID: 18376000]

34. Law M, Rudnicka AR.Statin safety: a sys-tematic review. Am JCardiol. 2006;97:52C-60C.[PMID: 16581329]

35. Sharma M, AnsariMT, Abou-Setta AM,et al. Systematic re-view: comparativeeffectiveness andharms of combina-tion therapy andmonotherapy fordyslipidemia. AnnIntern Med.2009;151:622-30.[PMID: 19884623]

36. Kashani A, PhillipsCO, Foody JM, et al.Risks associated withstatin therapy: a sys-tematic overview ofrandomized clinicaltrials. Circulation.2006;114:2788-97.[PMID: 17159064]


lipid levels. It is also important torealize that specific agents may bemore effective when used in com-bination, because they act syner-gistically to treat certain lipid ab-normalities. Combination therapycan lower LDL cholesterol levelbut can also lower triglyceride lev-els and raise HDL cholesterol levels,both secondary goals in lipid man-agement (29–31). Ezetimibe de-creases LDL cholesterol levels byblocking absorption through theintestine (30). Although ezetimibedecreases LDL cholesterol levels,clinical trials show that it does notreduce coronary events (30, 31).

Two major studies released in 2008showed no survival benefit of ezetimibewhen used in combination with statintherapy (32, 33). Because no clinical trialhas shown that ezetimibe decreases coro-nary events, it is not recommended as pri-mary therapy for patients with elevatedLDL cholesterol levels.

The lipid-lowering medicationsthat are combined most frequentlyinclude statins, bile acid–bindingresins, fibrates, and nicotinic acid.However, when prescribing com-bination therapy, the clinicianneeds to be vigilant for drug in-teractions. Fibrates should be usedwith caution when combined withstatins, particularly gemfibrozil,because they compete with thestatin for metabolism via the cy-tochrome P450 system. This in-teraction may induce rhabdomyol-ysis (34). Nicotinic acid, eithercrystalline or the extended-releaseniacin preparation (Niaspan), canbe effective with statins because itis complementary by raising HDLcholesterol levels and loweringtriglyceride levels. Cliniciansshould avoid using long-acting,nonflushing, over-the-counterniacin preparations, because theycan cause hepatotoxicity. A sys-tematic review found that high-dose stain monotherapy seems tobe superior to combination therapy (35).

What are the therapeutic goals oftreatment?Just like therapeutic decisions,treatment goals are individuallydetermined according to the pa-tient’s level of risk based on thepresence or absence of CAD,CAD risk equivalents, non–coronary vascular disease, andother risk factors (Box).

How should therapy fordyslipidemia be monitored?Most interventions to treat dyslipi-demia require at least 6 months toreduce the risk for CVD event rates(5), and treatment is usually life-long. Regular follow-up is impor-tant after initiation, but in the absence of strong evidence to sup-port a specific monitoring interval,it seems reasonable to schedule follow-up 6 weeks after the initia-tion of any new lipid-loweringagent with a fasting lipid profile.During this follow-up visit, the cli-nician should discuss adherence,identify side effects, and encouragelifestyle changes. The frequency offollow-up visits should depend onthe patient’s progress. Althoughsome authors advocate routinelymonitoring liver function tests be-fore each follow-up visit, statin-induced hepatotoxicity seems muchless common than previously be-lieved, so the American College ofPhysicians’ guideline on treatmentfor dyslipidemia in type 2 diabetesdoes not recommend routine liverfunction tests in patients treatedwith statins (36, 37).

More frequent visits may be re-quired to provide counseling aboutbehavioral lifestyle changes, whichgenerally require much supportfrom the clinician to foster adher-ence. Overall, only 39% of patientsreceiving drug therapy and only34% of patients receiving dietarytherapy reach their NCEP goal(38). New or additional drugsshould be added one at a time be-cause, if adverse reactions occur, it iseasier to determine which drug



Table 2. Drug Treatment for Lipid DisordersDrug Class and

Mechanism of Action Dose Benefits Side Effects Notes

Statins (HMG-CoA reductase) Atorvastatin Well-studied for Abnormal liver function Choice of drug for elevated LDL Partially inhibit HMG-CoA (10–80 mg/d) safety and efficacy tests (relatively cholesterol based on efficacy reductase, the rate-limiting Fluvastatin (20–40 mg in many trials: uncommon). Myositis/ and safety. The 6 statins are step of cholesterol synthesis. every night or 80 mg LDL cholesterol– myalgias (use with metabolized differently, allowing This induces LDL-receptor XL every night) lowering ranges fibrates increases risk). substitution if side effects occur. formation and the removal of Lovastatin (10–40 mg from 22% to 63% Rosuvastatin should not Used in combination with bile LDL cholesterol from blood. evening meal or 10–60 depending on drug. be given with warfarin acid–binding resins to synergistically

XL every night) or gemfibrozil. reduce LDL cholesterol. Use with Pravastatin (10–80 mg niacin and fibrates in patients

at bedtime) combined hyperlipidemia. Rosu-Rosuvastatin (5–40 mg/d) vastatin is newest and as well Simvastatin (5–80 mg studied as the other statins. Do

at evening meal) not use in pregnant or nursingwomen. Avoid with active liverdisease.

Bile acid sequestrants Colestipol (2 scoops 2 or Nonabsorbed with Unpleasant taste/texture, First-line drug to lower Interrupt bile acid reabsorption 3 times per day) long-term safety bloating, heartburn, cholesterol in children and in requiring bile acid synthesis Colsevelam hydrochloride established. LDL constipation, drug women with child-bearing from cholesterol. (three 625 mg tables cholesterol–lowering interaction (avoidable potential. Second-line drug with

2 times per day by 10% to 15%. by administrating drugs statins to synergistically induce [3.8 g total]) 1 h before or 4 h after LDL cholesterol receptors. Do not

meals). Triglyceride levels use if triglyceride levels >3.39 increase. mmol/L (>300 mg/dL) or in gas-

trointestinal motility disorder.Fibrates Gemfibrozil (600 mg Best triglyceride level- Nausea, skin rash. Use with Does not reliably reduce (and

Reduce VLDL synthesis and 2 times per day) reducing drugs, lowers caution if renal can increase) LDL cholesterol lipoprotein lipase. Fenofibrate (45–145 by 50% or more in insufficiency or gallbladder level. Use cautiously with statins

mg/d depending many patients. disease. due to myositis/myalgia. Use on brand) Increases HDL cho- with repaglinide may cause

lesterol level by 15%. severe hypoglycemia.

Ezetimibe 10 mg once per day Reduces LDL Well-tolerated, but contra- Can use with statins for further Selectively inhibits intestinal cholesterol level by indicated in patients with LDL cholesterol and triglyceride absorption of cholesterol 18%, triglyceride level liver disease or elevated level reduction and to increase and related phytosterols. by 8%, and apolipo- liver enzyme levels. HDL cholesterol level. Do not

protein B by 16%. combine with resins, fibrates, orcyclosporine.

Niacin Niacin (500–750 mg to Lowers LDL chol- Flushing, nausea, glucose Drug of choice for combined Largely unknown; reduces 1–2g every night of esterol and triglyceride intolerance, gout, liver hyperlipidemia and in patients hepatic production of extended-release niacin) levels 10% to 30%. function test abnormalities, with low HDL cholesterol level. B-containing lipoproteins. Most effective drug and elevated uric acid. Extended-release preparations Increases HDL cholesterol. to raise HDL chol- May increase limit flushing and liver function

esterol level (25% homocysteine. test abnormalities. Long-acting to 35%) OTC niacin preparations not recom-

mended, because they increase theincidence of hepatotoxicity. Lowerslipoprotein(a). Used in combinationwith statins or bile acid–bindingresins in patients with combined hy-perlipidemia. Do not use in pregnantor nursing women.

Omega-3 4–6 g/d with higher Effective in controlling Dyspepsia, nausea. May Can increase LDL cholesterol Polyunsaturated fatty acids inhi- dosing for OTC triglyceride levels up increase bleeding time. level in some patients with bit hepatic triglyceride synthesis formulations to 45%. Raises HDL Use cautiously in patients increased triglyceride levels.and augment chylomicron trigly- cholesterol level 13%. receiving anticoagulant ceride clearance secondary to therapy.increased activity of lipoprotein lipase.

Ezetimibe and simvastatin Ezetimibe, 10 mg Combination therapy Abnormal liver function Avoid use with fibrates, >1 g; (combination drug) every night may improve patient tests. Myositis, myalgia. niacin; amiodarone; or verapamil Both selectively inhibit the Simvastatin, 10– 80 mg adherence. Synergistic due to increased risk for myopathy. intestinal absorption of every night benefits. Contraindicated in liver disease and cholesterol and partially inhibit in pregnant or nursing women.HMG-CoA reductase

HDL = high-density lipoprotein; LDL = low-density lipoprotein; OTC = over-the-counter; VLDL = very low-density lipoprotein.


37. Clinical Efficacy As-sessment Subcom-mittee of the Ameri-can College ofPhysicians. Lipidcontrol in the man-agement of type 2diabetes mellitus: aclinical practiceguideline from theAmerican College ofPhysicians. Ann In-tern Med.2004;140:644-9.[PMID: 15096336]

38. Pearson TA, KopinLA. Compliance ofhealthcare profes-sionals with screen-ing and treatmentguidelines. In: BurkeLA, Ockene IS, eds.Compliance inHealthcare and Re-search. Armonk, NY:Futura Publishing;2001.

39. Armitage J. The safe-ty of statins in clini-cal practice. Lancet.2007;370:1781-90.[PMID: 17559928]

40. Link E, Parish S, Ar-mitage J, et al;SEARCH Collabora-tive Group. SLCO1B1variants and statin-induced myopa-thy—-agenomewide study.N Engl J Med.2008;359:789-99.[PMID: 18650507]

41. Bruckert E, Hayem G,Dejager S, et al. Mildto moderate muscu-lar symptoms withhigh-dosage statintherapy in hyperlipi-demic patients - PRI-MO study. Cardio-vasc Drugs Ther.2005;19(6):403-14[PMID: 16453090]

42. Ferdowsian HR,Barnard ND. Effectsof plant-based dietson plasma lipids. AmJ Cardiol.2009;104:947-56.[PMID: 19766762)

43. Swain JF, Rouse IL,Curley CB, Sacks FM.Comparison of theeffects of oat branand low-fiber wheaton serum lipopro-tein levels and bloodpressure. N Engl JMed. 1990;322:147-52. [PMID: 2152973]

44. Sabaté J, Oda K, RosE. Nut consumptionand blood lipid lev-els: a pooled analysisof 25 interventiontrials. Arch InternMed. 2010;170:821-7. [PMID: 20458092]


caused the problem. The NCEPATP III recommends that aftertreatment with the initial lipid-lowering agent is started, the clini-cian should reassess the fasting lipidprofile in 6 weeks to assess the re-sponse to therapy. If the LDL cho-lesterol goal is still not achieved,further intensification of therapyshould be considered, with re-evaluation in another 6 weeks (5).

What are the side effects of drugtherapy for dyslipidemia?The most common side effect ofstatins (HMG-CoA reductase in-hibitors) are myalgias, myositis, andelevated liver enzyme levels; howev-er, frequency of serious events is low,and rhabdomyolysis is rare. The inci-dence of myopathy due to statins is 1 per 10 000 patients per year (39).A study discovered that variations ina gene encoding a transporter pro-tein are linked to many cases ofstatin-induced myopathy (36).

A systematic review quantified the risks formusculoskeletal, renal, and hepatic com-plications associated with statin therapy.After examining data from 74 102 personsenrolled in 35 trials and followed for up to65 months, the authors concluded thatstatin therapy is associated with a smallexcess risk for aminotransferase elevations(risk difference per 1000 patients [RD], 4.2[95% CI, 1.5 to 6.9]) but not for myalgias(RD, 2.7 [CI, −3.2 to 8.7]), creatine kinase el-evations (RD, 0.2 [CI,−0.6 to 0.9]), rhab-domyolysis (RD, 0.4 [CI, −0.1 to 0.9]), orwithdrawal of therapy compared withplacebo (RD, −0.5 [CI, −4.3 to 3.3]) (40).

However, trial findings may differfrom the experience in actual clini-cal practice.

In a prospective, observational cohort (PRI-MO [Pexelizumab for Reduction in Infarctionand Mortality] study) of nearly 8000 Frenchpatients aged 18 to 75 years who receivedhigh-dose statins for at least 3 months,10.1% developed muscular pain, with 24.2%of these reported pain “all over” that oftencaused a disruption in daily activities. Themedian time to developing muscular symp-toms was 1 month, but 80% of those whodeveloped symptoms did so by 3 months af-ter initiating or intensifying the statin (41).

Fibrates can cause nausea and skinrash and must be used cautiouslywith statins, because the combina-tion tends to increase the incidenceof myositis and myalgias. The intes-tinal cholesterol absorption-blockingdrugs and the bile acid–bindingdrugs tend to cause abdominalbloating and constipation; otherwise,they are generally well-tolerated.Niacin is valuable and efficaciousbut probably the least well-toleratedlipid-lowering agent. However,community-based studies revealedhigher rates of muscle symptoms.

Niacin can cause flushing, nausea,headache, glucose intolerance, andgout. Some of these effects can beminimized with proper drug admin-istration. To minimize flushing, anonenteric-coated aspirin can betaken 1 hour before the eveningdose along with a low-fat snack. Pa-tients should also avoid hot bever-ages, baths, or showers around thetime of a niacin dose.

Clinicians should be vigilant forside effects when prescribing drugsfor dyslipidemia. Unfortunately, ev-idence is insufficient to establishclear recommendations regardingmonitoring and management ofside effects. When severe side ef-fects occur, discontinuation may bethe only option. Clinicians and pa-tients need to weigh the risks andbenefits of therapy with minor sideeffects. Because metabolism of thevarious statins differ, it may be rea-sonable to substitute one statin foranother when side effects occur.

What should clinicians advisepatients about the use ofcomplementary–alternativetherapies for dyslipidemia?Among commonly used alternativetherapies for controlling lipids,plant-based diets have shown someeffectiveness (42), including stanolester-containing margarines orfoods, oat bran (43), and nuts inmoderation (44). Some dietarychanges might affect serum lipidlevels merely by replacing fatty foods


45. Medicare Pay-for-Re-porting Program:Physicians QualityReporting Initiative(PQRI) Overview.American College ofPhysicians. Accessedatwww.acponline.org/running_practice/practice_manage-ment/payment_coding/pqri_gi.htm on22 June 2010.

46. Vijan S, Hayward RA;American College ofPhysicians. Pharma-cologic lipid-lower-ing therapy in type 2diabetes mellitus:background paperfor the AmericanCollege of Physi-cians. Ann InternMed. 2004;140:650-8. [PMID: 15096337]


with healthier choices. However,complementary–alternative therapiesshould not substitute for drug therapy in high-risk patients.

When should clinicians consult alipid specialist for help inmanaging patients withdyslipidemia?The clinician should consider con-sulting a lipid specialist for patientswith lipid disorders that are rare orresistant to treatment. These includethose patients with specific rare dis-orders that require either specialmonitoring or complex regimens thatare difficult to initiate in a routinepractice setting. Patients in this category may include those with fa-milial hypercholesterolemia, type IIIdyslipoproteinemia, very low HDL cholesterol syndromes (HDL cholesterol level <0.5 mmol/L

[<20 mg/dL]), and resistant hyper-triglyceridemia (triglyceride level>11.3 mmol/L [>1000 mg/dL]).Also, patients with a high risk for avascular event, such as young patientswith vascular disease before the ageof 45 years and patients with evi-dence of disease progression despitetreatment, are candidates for referralto a lipid specialist. Patients at veryhigh risk may need multiple inter-ventions to lower their LDL choles-terol level substantially below theusual LDL cholesterol goal, to raisetheir HDL cholesterol level, or toidentify and treat other lipid andnonlipid risk factors. Current treat-ments to lower LDL cholesterol levelare very efficacious; however, a poorresponse may prompt an examinationof secondary causes, such as unusuallipid and lipoprotein disorders orpoor adherence to medication.

Practice

Improvementapply to their patients from 1 Julythrough 31 December 2007 (45) andincludes a measure related to lipidcontrol in patients with diabetes.

What do professionalorganizations recommendregarding the care of patientswith dyslipidemia?As noted earlier, several organiza-tions offer recommendations aboutdyslipidemia screening that differwith respect to the age at whichscreening should be started andwhich screening tests should be used(5, 6). In addition, evidence-basedguidelines include an American College of Physicians’ guideline onlipid control in patients with type 2diabetes (46). A comprehensive

What measures do U.S. stake-holders use to evaluate the qualityof care for patients withdyslipidemia?In April 2005, the Ambulatory CareQuality Alliance released 26 healthcare quality indicators for clinicians,consumers, and health care pur-chasers to use in quality improve-ment efforts, public reporting, andpay-for-performance programs atwww.aqaalliance.org. In May 2005,the Centers for Medicare & Medi-caid Services endorsed the develop-ment of these indicators. Of the 26indicators, 3 focus on dyslipidemia.In addition, the voluntary MedicarePhysicians Quality Reporting Initia-tive pays physicians a bonus for re-porting on quality measures that

Treatment... Treatment of dyslipidemia should always include modification of dietand exercise to optimize lipid levels. Clinicians should base decisions on drugtherapy on the individual patient’s risk for cardiovascular events and should se-lect drugs that target the lipid abnormalities. Strong evidence supports statintherapy for high-risk patients.



inth

ec l

inic

Tool Kitin the clinic

Dyslipidemia

PIER Moduleshttp://PIER.acponline.org

Access the following PIER modules: Screening for Dyslipidemia, Lipid Disorders.PIER modules provide an evidence-based, electronic resource for clinical recommenda-tions and links to patient information materials at the point of care.

Practice Guidelineswww.ahrq.gov/clinic/uspstf/uspschol.htm

Access the U.S. Preventive Services Task Force recommendations on screening for dys-lipidemia (update anticipated in late 2007).

www.nhlbi.nih.gov/guidelines/cholesterol/index.htm

Access the National Cholesterol education Program Adult Treatment Panel III recom-mendations on detection, evaluation, and treatment of high cholesterol.

www.annals.org/cgi/reprint/140/8/644.pdf

Access the American College of Physicians’ guideline on pharmacologic treatment ofdyslipidemia in patients with type 2 diabetes.

Framingham Risk Calculatorhttp://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof

Use this calculator to estimate a person’s risk for cardiovascular events.

Patient Informationwww.annals.org/intheclinic/toolkit-dyslipidemia.html

Download a copy of the patient information sheet that appears on the following pagefor duplication and distribution to your patients.

www.doctorsforadults.com/images/healthpdfs/cholesterol_report.pdf

Obtain the patient information pamphlet, “Managing Your Cholesterol,” developed bythe American College of Physicians.

3 August 2010Annals of Internal MedicineIn the ClinicITC2-14© 2010 American College of Physicians

listing of guidelines is availablethrough the National GuidelineClearinghouse at www.guidelines.gov. However, the most widelyused lipid guideline in the United

States is the National Heart Lungand Blood Institute’s NCEP-ATPIII document, which is available atwww.nhlbi.nih.gov/guidelines/cholesterol/index.htm.

Figure. Treatment of dyslipidemia helps prevent this disease. Low magnifica-tion micrograph of the distal right coronary artery with complex atheroscle-rosis and luminal narrowing.


In the ClinicAnnals of Internal Medicine

Pati

ent

Info

rmat

ion

THINGS YOU SHOULDKNOW ABOUT LIPIDS(CHOLESTEROL)

Lipids (cholesterol) are fatty substances in the blood.Lipids can build up and clog blood vessels, whichcontributes to heart attack, stroke, or other forms ofheart disease. There are several types of lipids thataffect health: Your LDL cholesterol is a bad type ofcholesterol, whereas the HDL cholesterol is a goodtype that removes cholesterol build up.

Ideal lipid levels and the need to control lipid levelsdepend on whether a person is at greater risk forheart attacks or strokes. This risk is increased fordiabetes, high blood pressure, tobacco use, familyhistory of heart disease, or other factors thatincrease risk for heart attack and stroke. Talk aboutyour lipid levels with your doctor.

Things You Can Do to Control Lipids• Keep body weight normal (BMI, 18.5 to 24.9 kg/m2).

• Get fewer than 25% to 35% of your daily caloriesfrom fat, less than 7% of your calories fromsaturated fat, and less than 200 mg of cholesterolper day.

• Eat a diet that contains more plant-based foods(vegetables, fruits, grains) than animal-based foods(meat, dairy, eggs).

• Exercise at least 30 minutes on most days of theweek.

• Avoid all forms of tobacco.

• Drink no more than 1 to 2 alcoholic beverages perday.

For More Information

Web Sites With Good Information AboutLipidswww.nlm.nih.gov/medlineplus/cholesterol.htmlMedlinePLUS

www.americanheart.org/presenter.jhtml?identifier=4488American Heart Association

www.nhlbi.nih.gov/chd/why.htmwww.nhlbisupport.com/chd1/S2Tipsheets/foodgroup.htmNational Heart, Lung, and Blood Institute


4.

3.

CME Questions

3 August 2010Annals of Internal MedicineIn the ClinicITC2-16© 2010 American College of Physicians

A 57-year-old woman is seen after astenting procedure of the left maincoronary artery. The patient has type 2diabetes mellitus. Her father had amyocardial infarction at age 62 years.Current medications are rosuvastatin,40 mg/d; aspirin, 81 mg/d; andglipizide, 10 mg/d.

On physical examination, blood pressureis 152/92 mm Hg. Lungs are clear.Cardiac examination reveals no murmurs,and the point of maximal impulse is notdisplaced. Fasting lipid levels are asfollows: total cholesterol level, 5.18mmol/L (200 mg/dL); HDL cholesterollevel, 1.09 mmol/L (42 mg/dL); LDLcholesterol level, 3.13 mmol/L (121mg/dL); triglyceride levels, 2.07 mmol/L(183 mg/dL). Hemoglobin A

1clevel is

6.9%.

Which is the most appropriate treatmentfor this patient?

A. Add a second lipid-lowering drugB. Increase the dose of rosuvastatinC. Substitute fenofibrate for

rosuvastatinD. Substitute metformin for glipizide

A 63-year-old man is evaluated during afollow-up appointment. One month ago,he had a transient ischemic attack.Carotid ultrasonography revealed a 60%left internal carotid artery stenosis, andtransthoracic echocardiogram revealedleft ventricular hypertrophy. He iscurrently asymptomatic. He hashypertension and quit smoking 10 yearsago. He has no history of coronary arterydisease and no family history ofpremature coronary artery disease.Current medications arehydrochlorothiazide and aspirin. His LDLcholesterol level 6 months ago was 3.57mmol/L (138 mg/dL), and he has adheredto recommended lifestyle modifications,including diet and exercise.

On physical examination, blood pressureis 132/84 mm Hg. There are no focalneurologic abnormalities. Fasting lipid

levels are as follows: total cholesterollevel, 5.34 mmol/L (206 mg/dL); HDLcholesterol level, 1.3 mmol/L (50 mg/dL);LDL cholesterol level, 3.32 mmol/L (128mg/dL); triglyceride level, 1.63 mmol/L(144 mg/dL).

In addition to continuing therapeuticlifestyle changes, which is the mostappropriate management option for thispatient?

A. Add atorvastatinB. Add nicotinic acidC. Change hydrochlorothiazide to

amlodipineD. Change hydrochlorothiazide to

carvedilol

A 65-year-old man is evaluated during aroutine visit. His medical history includeshypertension controlled withhydrochlorothiazide. He is otherwisehealthy, however, he admits to asedentary lifestyle and no regularexercise program.

On physical examination, the bloodpressure is 125/85 mm Hg, the BMI is 30kg/m2, waist circumference 38 inches,and the remainder of the examination isunremarkable. Fasting lipid levels are asfollows: serum total cholesterol, 4.63mmol/L (184 mg/dL); serum triglyceridelevel, 2.26 mmol/L (226 mg/dL); serumHDL cholesterol level, 1.01 mmol/L (39mg/dL); serum LDL cholesterol level, 2.59mmol/L (100 mg/dL).

Which is the most appropriate next stepin the management of this patient?

A. Statin therapyB. Fibric acid derivative C. Serum LDL cholesterol particle-size

measurementD. Diet and exercise

A 50-year-old man has a routineevaluation. He has type 2 diabetesmellitus, diagnosed 5 years ago. Hereports measuring his plasma glucoselevel in the morning and sporadically

throughout the day and has noted nofoot or eye problems. Medical history isalso significant for hypertension,hyperlipidemia, and coronary arterydisease treated with stenting 3 yearsago. He reports rare episodes of chestpain. Medications include metformin,1000 mg twice daily; aspirin, 81 mg/d;lovastatin, 80 mg/d; lisinopril, 20 mg/d;and atenolol, 25 mg/d.

Physical examination findings, includingblood pressure of 120/80 mm Hg, areunremarkable. Lipid levels are as follows:hemoglobin A

1c, 6.9%; serum creatinine,

normal; serum potassium, normal; serumtotal cholesterol level, 4.78 mmol/L (185mg/dL); serum triglyceride level, 1.69mmol/L (150 mg/dL); serum HDLcholesterol level, 1.16 mmol/L (45mg/dL); serum LDL cholesterol level, 2.84mmol/L (110 mg/dL).

Which is the most appropriate next stepin the management of this patient?

A. Increase lovastatin doseB. Continue periodic monitoring of

serum cholesterol levelC. Substitute a higher-potency statin,

such as atorvastatin orrosuvastatin

D. Add gemfibrozil

1.

2.

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed athttp://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/

to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.


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