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CME Objective: To review current evidence for diagnosis, treatment, and practiceimprovement of stable ischemic heart disease.
The information contained herein should never be used as a substitute for clinicaljudgment.
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Why is it important to differen-tiate patients with SIHD frompatients with unstable angina?Stable angina is typically broughton by exertion or emotion. In con-trast, unstable angina symptomsare more random and unpredictableand often occur without an appar-ent trigger (see the Box: PrincipalPresentations of Unstable Angi-na). Patients with low-risk unsta-ble angina can be managed thesame way as patients with SIHD.However, patients with high-riskor intermediate-risk unstableangina should be managed moreaggressively than described inthese materials (4).
What other diseases might beconfused with SIHD?Some patients with symptoms sug-gesting SIHD have an overall clin-ical picture that suggests another
diagnosis (see the Box: AlternativeDiagnoses to Angina for PatientsWith Chest Pain).
Why is it important to estimatethe probability of diseaseseparately from the mortality riskwhen evaluating people withsuspected SIHD?It is important to identify pa-tients with a probability of CADlow enough (< 5%) that they canbenefit from studies looking forcauses of chest pain other thanCAD. The clinician should startthis process using the patient’sage, sex, and type of angina(Table 1 and the Box: ClinicalClassification of Chest Pain).Smoking history, hyperlipidemia,and diabetes mellitus increase thelikelihood of CAD for each typeof patient, with diabetes havingthe greatest influence.
Stable ischemic heart disease (SIHD) affects many millions of Ameri-cans, with associated annual costs measured in tens of billions of dol-lars. It is a leading cause of death in the United States. SIHD occurs
when coronary artery disease (CAD) reduces the blood supply to the heartand typically causes recurrent chest pain or pressure known as angina. Theangina is exacerbated by activity or stress, lasts for minutes not seconds orhours, and goes away with rest or medication. Timely diagnosis and optimaltreatment can reduce complications and mortality from SIHD.
Recent clinical guidelines are designed to improve clinical care for SIHD.For example, in 2011, the U.K. National Institute of Clinical Excellencereleased new guidance on the management of stable angina (www.nice.org.uk/guidance/CG126) Also, in 2012, a collaboration of professional organ-izations in the United States released new guidelines for diagnosis andmanagement (1-3).
Diagnosis
Principal Presentations ofUnstable Angina*Rest angina: Occurring at rest and
usually lasting >20 minutesNew-onset severe angina: Severe
onset within 2 months of initialpresentation
Increasing angina: Previouslydiagnosed angina with acrescendo pattern of occurrence(increasing in intensity, duration,and/or frequency)
*From reference 5.
Table 1. Pretest Likelihood of Coronary Artery Disease in Symptomatic Patients According to Age and Sex*Age, y Nonangina Chest Pain, %† Atypical Angina, %† Typical Angina, %†
* From reference 42. † See the Box: Clinical Classification of Chest Pain.
1. Fihn SD, Gardin JM,Abrams J, et al.ACCF/AHA/ACP/AATS/PCNA/SCAI/STSGuideline for the Di-agnosis and Manage-ment of Patients WithStable Ischemic HeartDisease: A Report ofthe American Collegeof Cardiology Foun-dation/AmericanHeart AssociationTask Force on Prac-tice Guidelines, andthe American Collegeof Physicians, Ameri-can Association forThoracic Surgery, Pre-ventive Cardiovascu-lar Nurses Associa-tion, Society forCardiovascular An-giography and Inter-ventions, and Societyof Thoracic Surgeons.Circulation.2012;126:e354-e471.
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How should information from thephysical examination be used toevaluate people with suspectedSIHD?The physical examination is oftennormal or nonspecific in patients withstable angina. It may, however, revealrelated conditions, such as heart fail-ure, valvular heart disease, or hyper-trophic cardiomyopathy. Signs thatsuggest CAD when they are presentduring chest pain and disappear withresolution of angina include an S3 orS4 gallop, mitral regurgitant murmur,bibasilar rales, paradoxically split S2,or chest wall heave.
Signs of congestive heart failure in-clude jugular venous pulsation, S3gallop, mitral regurgitation murmur,displaced apical impulse, pulmonarycrackles, diminished breath sounds,or dullness to percussion, abdomi-nojugular reflux, hepatomegaly, andlower extremity edema. Signs ofnoncoronary atherosclerotic vasculardisease that increase the probabilityof CAD include carotid bruit, di-minished or absent pedal pulses, oran abdominal aneurysm (6). Xan-thelasma and xanthomas (yellowpatches or plaques on the skincaused by lipid deposits) are signs ofhyperlipidemias.
What other preliminary testsshould be used to evaluate peoplewith suspected SIHD?ElectrocardiogramAll patients with suspected SIHDshould have a resting electrocardio-gram (ECG). Most patients withSIHD have a normal resting ECG,but pathologic Q waves indicate aprior myocardial infarction (MI).Also, left bundle branch block andsome other ECG abnormalities helpdetermine which stress test to selectfor patients who need stress testing.
Chest x-rayAll patients without an obvious non-cardiac cause of angina should have achest x-ray. Chest x-rays are frequent-ly normal in patients with stable angi-na, but they may find evidence of
CHF, which worsens the prognosis,and they may suggest causes of chestpain other than angina.
EchocardiographyRest echocardiography is not recom-mended for most patients with sus-pected angina. The clinician shouldconsider rest echocardiography whenpatients have signs or symptomssuggesting heart failure or cardiacvalvular lesions, a pathologic Q-waveon the ECG, or ECG findings ofcomplex ventricular arrhythmias.
Which diagnostic test shouldfollow the preliminaryassessment?The next diagnostic test should es-tablish or rule out the diagnosis ofCAD and at the same time estimatethe patient’s mortality risk, becauseinformation on mortality risk is necessary to choose among possibletherapies. For most patients the nextdiagnostic test should be a standardexercise ECG using as the diagnosticendpoint for ischemia ≥ 1 mm hori-zontal or down-sloping ST-segmentdepression at 80 ms after the J pointduring peak exercise. Once the diag-nosis is established, the Duke Tread-mill Score, which is based on thestandard exercise ECG, accuratelypredicts the mortality risk (see theBox: Duke Treadmill Score). Pa-tients with low-risk exercise tread-mill scores (≥ + 5) have an estimatedcardiac mortality rate of ≤ 1% peryear and usually do not require fur-ther risk assessment. Patients withintermediate exercise treadmill scores(< + 5 and ≥ – 10) may be stratifiedinto low-risk (appropriate for med-ical management) and high-risk(consider for revascularization)groups using follow-up stress imag-ing or coronary angiography (7). Patients with high-risk exercisetreadmill scores (< – 10) have an an-nual mortality of ≥ 3% and shouldbe considered for revascularization.
Some patients have an ECG thatcannot be interpreted during exercisebecause of left bundle branch block,
Alternative Diagnoses to Anginafor Patients With Chest Pain*
• 2. Provoked by exertion or emo-tional stress and
• 3. Relieved by rest or nitroglycerinAtypical anginaMeets 2 of the above characteristics
Nonanginal chest painMeets 1 or none of typical angina
characteristics*From reference 41.
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2. Qaseem A, Fihn SD,Williams S, Dallas P,Owens DK, Shekelle P,for the Clinical Guide-lines Committee ofthe American Collegeof Physicians. Diagno-sis of Stable IschemicHeart Disease: Sum-mary of a ClinicalPractice GuidelineFrom the AmericanCollege of Physicians/American College ofCardiology Founda-tion/American HeartAssociation/ Ameri-can Association forThoracic Surgery/Pre-ventive Cardiovascu-lar Nurses Associa-tion/Society ofThoracic Surgeons.Ann Intern Med.2012;157:729-34.
3. Qaseem A, Fihn SD,Williams S, Dallas P,Owens DK, Shekelle P,for the Clinical Guide-lines Committee ofthe American Collegeof Physicians. Man-agement of Stable Is-chemic Heart Disease:Summary of a ClinicalPractice GuidelineFrom the AmericanCollege of Physi-cians/American Col-lege of CardiologyFoundation/AmericanHeart Association/American Associationfor ThoracicSurgery/PreventiveCardiovascular NursesAssociation/Society ofThoracic Surgeons.Ann Intern Med.2012;157:735-43.
4. Anderson JL, AdamsCD, Antman EM, et al.American College ofCardiology Founda-tion/American HeartAssociation Task Forceon Practice Guide-lines. 2012 ACCF/AHAfocused update incor-porated into theACCF/AHA 2007guidelines for themanagement of pa-tients with unstableangina/non-ST-eleva-tion myocardial infarc-tion: a report of theAmerican College ofCardiology Founda-tion/American HeartAssociation Task Forceon Practice Guide-lines. Circulation.2013;127:e663-828.
Other noninvasive tests are beingused at some institutions, includingcardiac computed tomography an-giography and stress with cardiacmagnetic resonance imaging. Thesetests are not generally available, andmost observers believe we need toknow more about them before rec-ommending widespread use.
When should clinicians referpatients with suspected SIHD tospecialists?Clinicians should consider consultinga cardiologist for patients with an un-certain diagnosis after noninvasivetesting and for patients in whomnoninvasive testing is contraindicated.
When should coronaryangiography be used as the initialtest to evaluate people withsuspected SIHD?Some patients should have coronaryangiography instead of noninvasivetests to establish the diagnosis ofCAD and to assess its mortalityrisk. Included are patients who havesurvived sudden cardiac death or alife-threatening ventricular arrhyth-mia, patients who have a high likeli-hood of severe CAD, patients inwhom coronary artery spasm isstrongly suspected, and some pa-tients with heart failure. For otherpatients, such as airplane pilots, firefighters, and police officers, theemployer may require coronary an-giography before allowing a returnto work, regardless of the resultsfrom noninvasive testing.
ventricular pacing, or some otherECG abnormality. A patient whoseECG is not interpretable during ex-ercise because of left bundle branchblock should have a pharmacologicstress test using imaging during thetest to replace ECG monitoring,with imaging based either on ra-dionuclide perfusion of the my-ocardium or echocardiography. Apatient whose ECG is not inter-pretable during exercise because ofabnormalities other than left bundlebranch block should have an exercisestress test with imaging, using eitherradionuclide perfusion of the my-ocardium or echocardiography.
Some patients cannot exercise orcannot exercise strenuously enoughto generate a valid test result. Thesepatients should have a pharmacolog-ic stress test with imaging, using ei-ther radionuclide perfusion of themyocardium or echocardiography.
Although a low coronary artery cal-cium score reliably identifies peoplewithout CAD, a high score is less reliable in ruling in CAD, which iswhy the role of this technology inevaluating patients with suspectedSIHD remains uncertain. Some ex-perts recommend it for patients withatypical symptoms who are at lowrisk for CAD because a low scoremight help rule out CAD. Other ex-perts recommend it for patients withan intermediate risk after initialstress testing because it might helpdecide next steps for assessing risk.
DIAGNOSIS... The most useful preliminary predictors of clinically significant CAD arethe patient’s age, sex, and type of chest pain, but smoking history, hyperlipidemia, anddiabetes mellitus are also useful. Information from the physical examination can iden-tify cardiac disease other than CAD and comorbid diseases that exacerbate angina. Allpatients should have a resting ECG, and nearly all patients should have a chest x-ray.Most patients should have a standard exercise ECG test as the initial noninvasive testfor measuring the probability of CAD and estimating the mortality risk. The clinicianshould consider coronary angiography instead of noninvasive testing for a specific andlimited subset of patients. The clinician should consider consulting a cardiologist forpatients with an uncertain diagnosis after noninvasive testing and for patients inwhom noninvasive testing is contraindicated.
CLINICAL BOTTOM LINE
Duke Treadmill Score*Duke Treadmill Score = Minutes of
exercise − (5 × maximal mm of ST deviation) – (0 for no chestpain, 4 for angina with exertion,or 8 if angina is the reason forstopping the test).
*From reference 8.
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5. Kumar A, Cannon CP.Acute Coronary Syn-dromes: Diagnosisand Management,Part I. Mayo Clin Proc.2009;84:917-38.
6. Pryor DB, Shaw L, Har-rell FE Jr, et al. Esti-mating the likelihoodof severe coronary ar-tery disease. Am JMed. 1991;90:553-62.
7. Hachamovitch R,Berman DS, Kiat H, etal. Incremental prog-nostic value ofadenosine stress my-ocardial perfusionsingle-photon emis-sion computed to-mography and im-pact on subsequentmanagement in pa-tients with or sus-pected of having my-ocardial ischemia. AmJ Cardiol.1997;80:426-33.
8. Mark DB, Hlatky MA,Harrell FE Jr, et al. Ex-ercise treadmill scorefor predicting prog-nosis in coronary ar-tery disease. Ann In-tern Med.1987;106:793-800.
9. Ford ES, Ajani UA,Croft JB, et al. Explain-ing the decrease inU.S. deaths from coro-nary disease, 1980-2000. N Engl J Med.2007;356:2388-98.
of the benefits and potential sideeffects of medications and theproper method of administeringmedications. Any limitations onphysical activity, including sexualactivity, should be addressed.
Patients should be instructed onwhen to seek medical help. In par-ticular, they should know the warn-ing signs and symptoms of MI andwhen to use aspirin and nitroglyc-erin. They should know how to con-tact emergency medical personneland where to find the nearest hospi-tal with 24-hour emergency cardio-vascular services. Consider advisingCPR training for family members.
Patients may also benefit fromgroup education, which is often be-haviorally oriented. It may involvemotivational reminders for lifestylechange received on their mobiletelephone and recommendations toaccess health information Websites. Home blood pressure (BP),blood glucose monitoring, and oth-er self-monitoring techniques cansupport lifestyle change.
Factors that may complicate patienteducation include low literacy, emo-tional disorders, social isolation, cul-tural beliefs, environmental factors,poverty, advanced age, and complexcomorbid conditions. These factorsmay impair a patient’s ability to ad-here to recommended medical ther-apies and lifestyle changes.
Which risk factors should bemodified?About half of the decline in cardio-vascular mortality observed duringthe past 40 years has been due tointerventions directed at risk fac-tors. According to 1 analysis, low-ering total cholesterol accountedfor approximately 24% of the ob-served mortality reduction, lower-ing systolic BP for 20%, reducingsmoking for 12%, and increasingphysical activity for 5% (9).
What are the goals of treatment?The main goals are minimizing thelikelihood of death while maximiz-ing health and function. Morespecifically, these goals include re-ducing premature cardiovasculardeath while preventing complica-tions of SIHD that impair patients’functional well-being, includingacute MI and heart failure; elimi-nating ischemic symptoms to theextent possible; and maintaining orrestoring a level of activity andquality of life that is satisfactory tothe patient. This approach ac-knowledges that some treatmentsare intended more to improve sur-vival while others are intendedmore to reduce symptoms, al-though many treatments helpachieve both goals at the same time(see the Box: Strategies for Achiev-ing Treatment Goals).
What is “guideline-directedmedical therapy” for patients withSIHD?A specific combination of treat-ments that is appropriate for mostpatients is called “guideline-directedmedical therapy” (Figure 1) (3) andshould be instituted regardless ofwhether revascularization occurs.
What is the role of patienteducation?Patient education plays a crucial rolein reducing risk factors and improv-ing medication adherence in pa-tients with SIHD. It should includeinformation about the underlyingdisease process and therapeutic op-tions, including the anticipatedrisks, costs, and outcomes.
Individualized patient educationtends to improve adherence tomedical therapy and patient satis-faction. It should focus on review-ing individual prognosis, importantrisk factors and lifestyle modifica-tions, behavioral approaches, andmedications that reduce these riskfactors. It should include a review
Treatment
Strategies for AchievingTreatment GoalsPatient educationLifestyle modificationMedical therapyRevascularization (coronary artery
bypass grafting or percutaneouscoronary intervention)
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Therefore, reducing risk factorsshould be pursued as intensively asis reasonable, and initial patientmanagement should focus oneliminating unhealthy behaviorsand on promoting weight loss,physical activity, and a heart-healthy diet (2).
Smoking cessationSmoking increases cardiovascular dis-ease mortality by 50% (10). Amongnondrug therapies, smoking cessationconfers the greatest possibility of riskreduction. Physicians should system-atically identify all tobacco users andrecommend smoking cessation at each
Figure 1. Guideline-directed medical therapy for patients with stable ischemic heart disease. ACCF = American College of Cardiology Foundation;ACEI = angiotensin-converting enzyme inhibitor; AHA = American Heart Association; ARB = angiotensin-receptor blocker; ASA = aspirin; ATP III =Adult Treatment Panel III; BP = blood pressure; CCB = calcium-channel blocker; CKD _chronic kidney disease; JNC VII = Seventh Report of theJoint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; LV = left ventricular; MI = myocardial in-farction; NHLBI = National Heart, Lung, and Blood Institute; NTG = nitroglycerin. From reference 3. Reprinted with permission from the AmericanCollege of Physicians. * The use of bile acid sequestrant is relatively contraindicated when triglyceride levels are 200 mg/dL or greater and is contraindicated whentriglyceride levels are 500 mg/dL or greater.† Dietary supplement niacin must not be used as a substitute for prescription niacin.
Successfultreatment?
Successfultreatment?
Stable Ischemic Heart Disease
Angina
Drug therapyto achieve BP
<140/90 mm HgConsider ACEI/ARBif LV dysfunction,
diabetes, CKD
Considerrevascularization
to improvesymptoms
Guideline-directedmedical therapy
with ongoingpatient education
β-blockerif no contraindication(especially if prior MI,heart failure, or other
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10. Reducing the healthconsequences ofsmoking: 25 years ofprogress: a report ofthe Surgeon General.Rockville, MD: U.S.Department ofHealth and HumanServices, PublicHealth Service, CDC,Center for ChronicDisease Preventionand Health Promo-tion, Office on Smok-ing and Health; 1989.DHHS publicationno. (CDC) 89-8411.
11. Kottke TE, BattistaRN, DeFriese GH,Brekke ML. Attrib-utes of successfulsmoking cessationinterventions inmedical practice. Ameta-analysis of 39controlled trials.JAMA.1988;259:2883-9.
12. Taylor CB, Houston-Miller N, Killen JD,DeBusk RF. Smokingcessation after acutemyocardial infarc-tion: effects of anurse-managed in-tervention. Ann In-tern Med.1990;113:118-23.
13. Goldberg AC,Ostlund RE, Jr., Bate-man JH, et al. Effectof plant stanoltablets on low-den-sity lipoprotein cho-lesterol lowering inpatients on statindrugs. Am J Cardiol.2006;97:376-9.
14. Hallikainen MA,Sarkkinen ES, Uusitu-pa MI. Plant stanolesters affect serumcholesterol concen-trations of hypercho-lesterolemic menand women in adose-dependentmanner. J Nutr.2000;130:767-76.
15. Nguyen TT, Dale LC,von BK, et al. Choles-terol-lowering effectof stanol ester in aUS population ofmildly hypercholes-terolemic men andwomen: a random-ized controlled trial.Mayo Clin Proc.1999;74:1198-206.
16. Chen JT, Wesley R,Shamburek RD, et al.Meta-analysis of nat-ural therapies for hy-perlipidemia: plantsterols and stanolsversus policosanol.Pharmacotherapy.2005;25:171-83.
clinic visit, because consistent, directphysician reminders to stop smokingincrease smoking cessation (11). Pa-tients with symptomatic CAD areparticularly receptive to treatment di-rected at smoking cessation (12). Pa-tients who are receptive should behelped to develop a cessation plan thatincludes both drug (nicotine replace-men, bupropion) and nondrug (smok-ing cessation programs) approaches.
Physical activityRegular exercise reduces coronaryheart disease mortality and may re-duce angina and improve functionalcapacity. Physicians should encour-age persons with chronic stableangina to incorporate moderateaerobic physical activity, such as 30 minutes of brisk walking, atleast 5 days a week. Resistancetherapy is also well-tolerated andassociated with improvements inquality of life, strength, and en-durance when added to a programof regular aerobic exercise, althoughit has not been extensively evaluat-ed in patients with SIHD. Patientsat high risk for cardiac complica-tions should participate in a med-ically supervised program for 8 to12 weeks to establish the safety ofthe prescribed exercise regimen.
Dietary modificationAn unhealthy diet contributes todyslipidemia, hypertension, obesity,and diabetes mellitus. In contrast,consuming a diet that is low in sat-urated fat, cholesterol, trans-fattyacids, and sodium and rich in freshfruits, vegetables, and whole grainscan reduce serum cholesterol andcardiovascular risk. Consumptionof omega-3 fatty acids in the formof fish (3 servings per week) or incapsule form (1 g/day [2 to 4 g/dayfor treatment of elevated triglyc-erides]) can also reduce risk in patients with SIHD. Plant stanols/sterols (2 g/day) can lower low-density lipoprotein (LDL) choles-terol by 5% to 15%, and the addition of viscous fiber (> 10 g/day)can reduce LDL cholesterol by 3%
to 5% (13-16) If alcohol is part ofthe diet, consumption should bemoderate.
Lipid managementA combination of therapeuticlifestyle interventions, such as di-etary modification with increasedexercise activity, along withHMG-COA reductase inhibitors(statins) should be used for lipidmanagement, unless contraindicat-ed or adverse events occur. Al-though previous guidelines recom-mended titrating statin doses totarget levels for LDL cholesterol,current guidelines recommendstandard doses of statins for pa-tients in specific risk categories.For example, in patients with sta-ble angina, the guidelines recom-mend high-intensity statin therapy(atorvastatin 80 mg or rosuvastatin20 mg) for patients ≤ 75 y andmoderate-intensity statin therapy(atorvastatin 10 mg, rosuvastatin10 mg, and other doses for otherstatins) for patients > 75 y (17).For patients who do not toleratestatins, ezetimibe, plant stanol/sterols, and omega-3 fatty acidsmay be considered, although theyhave not been shown to improveclinical outcomes.
BP controlHypertension is an important inde-pendent risk factor for coronaryheart disease events. Various studieshave demonstrated a continuous andgraded relationship between BP andcardiovascular risk.
A meta-analysis of prospective studies ofnearly 1 million adults without preexistingvascular disease found that risk for vascu-lar death increased linearly over the BPrange of 115/75 mm Hg to 185/115 mmHg, without a threshold effect. Each incre-ment of 20 mm Hg in systolic BP or 10 mmHg in diastolic BP was associated with adoubling of risk (18).
An overview of 17 placebo-controlled trialsshowed that a reduction of 5 to 6 mm Hg indiastolic BP (or an estimated 10 to 20 mmHg in systolic BP) was associated with a sig-nificant reduction in vascular mortality,
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with an approximately 40% reduction instroke and 20% reduction in coronaryevents (19).
In many patients, therapy with antihypertensive medications is required to lower BP. There is noestablished optimal threshold ofbenefit with regard to reduction inBP levels (3). There are, however,reasons for caution in intensive BPlowering in patients with SIHDbecause excessive reduction in dias-tolic BP may compromise coronaryperfusion.
Psychological well-beingInterventions to reduce psychologi-cal stress may improve clinical out-comes in patients with SIHD (19).Clinicians may recommend thatpatients seek counseling or stressmanagement interventions, likemeditation, to reduce risks and improve well-being.
Which medical therapies canprevent MI or death?Antiplatelet therapyBecause platelet aggregation is akey element of the thrombotic re-sponse to plaque disruption, plate-let inhibition is recommended inpatients with SIHD.
Among 2920 patients with SIHD, a meta-analysis associated aspirin use with a 33% re-duction in the risk for serious vascular events,including a 46% decrease in the risk for unstable angina and a 53% decrease in therisk for requiring coronary angioplasty (20)
A meta-analysis of 145 randomized trialsfound an association between medium-dose aspirin (75 to 325 mg/d) and a 27% reduction in the odds ratio for major cardio-vascular events over 5 years in patients withknown coronary or vascular disease (21).
A meta-analysis from the U.S. PreventiveServices Task Forces concluded that aspirinreduces cardiovascular disease in patients,with men having fewer MIs and womenhaving fewer ischemic strokes (22).
Therefore, in the absence of con-traindications, all patients withSIHD should receive aspirin thera-py and continue it indefinitely. A
dose of 75 to 162 mg daily is as effective as higher doses and is associated with a lower risk forbleeding. When aspirin is con-traindicated, patients can be treatedwith clopidogrel 75 mg daily.
Influenza vaccinePatients with SIHD should receivean annual influenza vaccine (23).
ACE inhibitorsAngiotensin-converting enzyme(ACE) inhibitors should be pre-scribed for patients with SIHDwho also have hypertension, dia-betes, left ventricular (LV) systolicdysfunction (ejection fraction < 40%) or chronic kidney disease.For example, ACE inhibitors re-duce mortality, composite cardio-vascular events, MI, and stroke inpatients with LV ejection fraction< 35% or diabetes and ≥ 1 addi-tional cardiovascular risk factor.
In the CONSENSUS trial, enalapril titratedto 40 mg/d in patients with class IV CHF re-duced mortality by 18% at 6 months (NNT= 5.5) (24).
In the SOLVD treatment trial, enalapriltitrated to 20 mg/d in patients with class IIand III CHF reduced mortality by 4.5% at 3 years (NNT = 22) (25).
In the SOLVD prevention trial, enalapriltitrated to 20 mg/d in patients withasymptomatic LV dysfunction reduceddeath from CHF, hospitalization for CHF,and the composite outcome of death ordevelopment of CHF (26).
In the HOPE trial, patients with vasculardisease or diabetes and ≥ 1 additional car-diovascular risk factor who were treatedwith ramipril, 10 mg/d for an average of4.5 years, had significantly reduced risk forcardiovascular events (27).
Angiotensin-receptor blockersWhen ACE inhibitors are contra-indicated, angiotensin-receptor block-ers should be prescribed for patientswith SIHD who also have hyperten-sion, diabetes, LV systolic dysfunction(ejection fraction < 40%), or chronickidney disease (28).
17. Stone NJ, RobinsonJ, Lichtenstein AH, etal. 2013 ACC/AHAGuideline on theTreatment of BloodCholesterol to Re-duce AtheroscleroticCardiovascular Riskin Adults: A Reportof the American Col-lege ofCardiology/Ameri-can Heart Associa-tion Task Force onPracticeGuidelines.Circula-tion. 2013 Nov 12.[Epub ahead ofprint]
18. Lewington S, ClarkeR, Qizilbash N, et al.Age-specific rele-vance of usual bloodpressure to vascularmortality: a meta-analysis of individualdata for one millionadults in 61 prospec-tive studies. Lancet.2002;360:1903-13.
19. Collins R, Peto R. An-tihypertensive drugtherapy: effects onstroke and coronaryheart disease. In:Swales JD, editor.Textbook of Hyper-tension. BlackwellScientific Publica-tions, 1994.
21. Collaborative meta-analysis of ran-domised trials of an-tiplatelet therapy forprevention of death,myocardial infarc-tion, and stroke inhigh risk patients.BMJ. 2002;324:71-86.
22. Collaborativeoverview of ran-domised trials of an-tiplatelet therapy–I:Prevention of death,myocardial infarc-tion, and stroke byprolonged an-tiplatelet therapy invarious categories ofpatients. AntiplateletTrialists’ Collabora-tion. BMJ.1994;308:81-106.
23. Wolff T, Miller T, Ko S.Aspirin for the pri-mary prevention ofcardiovascularevents: an update ofthe evidence for theU.S. Preventive Serv-ices Task Force. AnnIntern Med.2009;150:405-10.
24. de Diego C, Vila-Cor-coles A, Ochoa O, etal. Effects of annualinfluenza vaccina-tion on winter mor-tality in elderly peo-ple with chronicheart disease. EurHeart J. 2008;30:209-16.
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25. Effects of enalaprilon mortality in se-vere congestiveheart failure. Resultsof the CooperativeNorth ScandinavianEnalapril SurvivalStudy (CONSENSUS).The CONSENSUS Tri-al Study Group. NEngl J Med.1987;316:1429-35.
26. Effect of enalapril onsurvival in patientswith reduced leftventricular ejectionfractions and con-gestive heart failure.The SOLVD Investi-gators. N Engl J Med.1991;325:293-302.
27. Yusuf S, Pepine CJ,Garces C, et al. Effectof enalapril on my-ocardial infarctionand unstable anginain patients with lowejection fractions.Lancet.1992;340:1173-8.
28. Yusuf S, Sleight P,Pogue J, et al. Effectsof an angiotensin-converting-enzymeinhibitor, ramipril, oncardiovascularevents in high-riskpatients. The HeartOutcomes Preven-tion EvaluationStudy Investigators.N Engl J Med.2000;342:145-53.
29. Turnbull F, Neal B, Pf-effer M, et al. Bloodpressure-dependentand independent ef-fects of agents thatinhibit the renin-an-giotensin system. JHypertens.2007;25:951-8.
31. Packer M, BristowMR, Cohn JN, et al.The effect ofcarvedilol on mor-bidity and mortalityin patients withchronic heart failure.U.S. Carvedilol HeartFailure Study Group.N Engl J Med.1996;334: 1349-55.761.
32. Leizorovicz A, LechatP, Cucherat M, et al.Bisoprolol for thetreatment of chronicheart failure: a meta-analysis on individ-ual data of twoplacebo-controlledstudies—CIBIS andCIBIS II. Cardiac In-sufficiency Bisopro-lol Study. Am HeartJ. 2002;143:301-7.
β-blocker therapyMetoprolol succinate, carvedilol, orbisoprolol should be prescribed forpatients with LV systolic dysfunc-tion (ejection fraction < 40%) andheart failure or prior MI (29-31).
Alternative therapiesVitamins and mineral supplementsare not recommended for prevent-ing CAD events (32, 33).
Which medical therapies relievesymptoms?A range of drugs are available thatare effective at reducing symptoms,including β-blockers, calcium-channel blockers, and nitrates. All ofthe classes of agents seem to be rela-tively similar in antianginal efficacyand have acceptable safety and toler-ability profiles. Comparative trialsamong these medications are rela-tively few and for the most partsmall. Because β-blockers have beenshown to improve survival in pa-tients after acute MI and have along history of clinical use, they areconsidered first-line drugs for treat-ing angina. In patients who do nottolerate or adequately respond to β-blockers, calcium-channel block-ers or long-acting nitrates may besubstituted or added (34).
Short-acting nitratesSublingual nitroglycerin or nitro-glycerin spray should be used forimmediate relief of angina.
β-blocker therapyβ-blockers should be prescribedas initial therapy for relief ofsymptoms. Expert panels recom-mend titrating β-blockers to aresting heart rate of 55 to 60beats/min.
Calcium-channel blockers and long-acting nitratesCalcium-channel blockers orlong-acting nitrates can be pre-scribed when β-blockers are con-traindicated or produce unaccept-able side effects. When β-blockersare ineffective, calcium-channelblockers or long-acting nitrates
can be prescribed in addition to orinstead of β-blockers (35).
RanolazineRanolazine is a recently approveddrug that shares characteristics withcalcium-channel blockers but seemsto act via different mechanisms.Consider using ranolazine when β-blockers are contraindicated orproduce unacceptable side effects.Consider using ranolazine com-bined or instead of β-blockers if β-blockers are ineffective (36, 37).
Alternative therapiesAlternative therapies, includingspinal cord stimulation, enhancedexternal counterpulsation, andtransmyocardial revascularization,may be considered for relief of re-fractory angina in patients withSIHD (1).
Which patients are candidates forrevascularization with eithercoronary artery bypass graftsurgery (CABG) or percutaneouscoronary intervention (PCI)?Consider revascularization to im-prove survival in patients withSIHD who are at high risk formortality, and consider revascular-ization to relieve persistent symp-toms despite an adequate trial ofguideline-directed medical therapy(Figures 1 and 2).
When patients are candidates forrevascularization to improvesurvival, which patients shouldhave CABG, and which patientsshould have PCI?Patients with SIHD at high risk formortality are candidates for revascu-larization to improve survival andshould have coronary angiography.Revascularization should not bedone to improve survival if coronaryangiography reveals stenoses that arenot anatomically or functionally sig-nificant, involve only the left circum-flex artery or right coronary artery, oraffect only a small area of viable my-ocardium. If coronary angiographyfinds left main CAD or complexCAD, the decision between either
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33. Brown BG, Zhao XQ,Chait A, et al. Sim-vastatin and niacin,antioxidant vitamins,or the combinationfor the prevention ofcoronary disease. NEngl J Med.2001;345:1583-92.
34. Fortmann SP, BurdaBU, Senger CA, et al.Vitamin and mineralsupplements in theprimary preventionof cardiovascular dis-ease and cancer: anupdated systematicevidence review forthe U.S. PreventiveServices Task Force.Ann Intern Med.2013;159:824-34.
35. Shaw LJ, Berman DS,Maron DJ, et al. Opti-mal medical therapywith or without per-cutaneous coronaryintervention to re-duce ischemic bur-den: results from theClinical OutcomesUtilizing Revascular-ization and Aggres-sive Drug Evaluation(COURAGE) trial nu-clear substudy. Cir-culation.2008;117:1283-91.
type of revascularization should in-volve the patient, a cardiac surgeon,and an interventional cardiologist.CABG is recommended when thepatient has stenosis of the left maincoronary artery that is ≥50% of thelumen diameter or stenosis of ≥70%in 3 major coronary arteries orstenosis of ≥70% in the proximal leftanterior descending artery and 1other major coronary artery. Eithermethod can be used for survivors ofsudden cardiac death with presumedischemia-mediated ventricular tachy-cardia caused by ≥70% stenosis in amajor artery.
When patients are candidates for revascularization to relievesymptoms, which patients shouldhave CABG and which patientsshould have PCI?Patients who have persistent symp-toms despite an adequate trial ofguideline-directed medical therapy(Figure 2) are candidates for revascu-larization to relieve symptoms andshould have coronary angiography.When the patient has the types ofstenosis described previously that arelikely to affect survival, the same rec-ommendations apply. Either CABGor PCI is recommended for otherpatients who have ≥70% stenosis in1 or more coronary arteries.
Are there special considerationsfor women, older adults, orpatients with diabetes mellitus,chronic kidney disease, or otherconditions?Special considerations for diagnosisand therapy may be warranted in pa-tients with certain clinical features.
WomenWomen generally have a lower in-cidence of SIHD than men untilolder age but outcomes after MIare worse. Microvascular diseaseand coronary spasm are more com-mon in women, and obstructingepicardial CAD is less prevalent.Stable angina is the most commoninitial manifestation of SIHD inwomen, as opposed to acute MI
and sudden death in men. Atypicalchest pain and angina-equivalentsymptoms, such as dyspnea, aremore common in women, althoughthe patterns, duration, and frequen-cy of symptoms in women are simi-lar to those in men.
Such differences in presentationand testing may account, in part,for discrepancies in care betweenmen and women with coronary dis-ease. Women receive aspirin andother antithrombotics less fre-quently than men and are less likelyto have revascularization.
Older adultsIn adults older than 75 years, coro-nary stenoses tend to be more dif-fuse and severe, with a higherprevalence of 3-vessel and left maindisease. Common coexisting condi-tions of the pulmonary, gastroin-testinal, and musculoskeletal systems can cause chest pain, mak-ing diagnosis more difficult, even inpatients with documented SIHD.Stress testing is more difficult dueto physiologic changes associatedwith aging, including alterations incardiac output, muscle loss, neu-ropathies, lung disease, and degen-erative joint disease. Baseline ECGchanges, arrhythmias, and LV hy-pertrophy, which are more commonin older adults who have accumu-lated cardiac comorbid conditions,limit the value of stress testing. Thehigher prevalence of SIHD in olderadults causes more false-negativeresults, although stress testing stillprovides useful information formanagement.
Several studies have shown less fre-quent use of evidence-based thera-pies in older adults. This may bebecause pharmacotherapy is moredifficult in older adults. A moreconservative approach to coronaryangiography is often appropriategiven the higher risk for contrast-induced side effects. Morbidity andmortality from CABG are increasedin older adults.
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36. Heidenreich PA, Mc-Donald KM, Hastie T,et al. Meta-analydsisof trials comparingbeta-blockers, calci-um antagonists, andnitrates for stableangina. JAMA.1999;281:1927-36.Rousseau MF,Pouleur H, Cocco G,et al. Comparativeefficacy of ra-nolazine versusatenolol for chronicangina pectoris. AmJ Cardiol.2005;95:311- 6.
37. Chaitman BR, PepineCJ, Parker JO, et al.Effects of ranolazinewith atenolol, am-lodipine, or diltiazemon exercise toler-ance and angina fre-quency in patientswith severe chronicangina: a random-ized controlled trial.JAMA. 2004;291:309-16.
Figure 2. Revascularization to improve symptoms of patients with stable ischemic heart disease. CABG = coronary artery bypass grafting; PCI = percutaneous coronary intervention.
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38. Farkouh ME, Do-manski M, SleeperLA, et al; FREEDOMTrial Investigators.Strategies for multi-vessel revasculariza-tion in patients withdiabetes. N Engl JMed. 2012;367:2375-84. N Engl J Med.2012; 367:2375-84.
39. De Bruyne B, PijlsNH, Kalesan B, Bar-bato E, Tonino PA,Piroth Z, et al; FAME2 Trial Investigators.Fractional flow re-serve-guided PCIversus medical ther-apy in stable coro-nary disease. N EnglJ Med. 2012;367:991-1001.
40. Gibbons RJ, AbramsJ, Chatterjee K, et al;American College ofCardiology.ACC/AHA 2002guideline update forthe management ofpatients with chron-ic stable angina—summary article: areport of the Ameri-can College of Cardi-ology/AmericanHeart AssociationTask Force on prac-tice guidelines(Committee on theManagement of Pa-tients With ChronicStable Angina). J AmColl Cardiol.2003;41:159-68.
Diabetes mellitusType 1 and type 2 diabetes mellitusincrease risk for SIHD and magni-fy the effects of other risk factors,such as hypercholesterolemia. Mor-tality risk for SIHD among diabet-ics is equivalent to that of personswith previous MI. Intensive andearly diagnosis and managementare important, as is a focus onachievement and maintenance ofoptimal blood sugar control, lipidmanagement, and attention to oth-er risk factors.
Among patients with CAD, con-comitant diabetes increases the riskfor adverse events with both medicaltherapy and revascularization. CABGmay be preferable to PCI in thesepatients, but the data are evolving.
Chronic kidney diseaseChronic kidney disease confersgreater risk for SIHD, for progres-sion of SIHD, and for poor out-comes after interventions for AMI.To avoid these complications,physicians should consider creati-nine clearance when choosing anddosing drugs, risk scores for pre-dicting contrast-induced nephropa-thy, and renal protective strategiesduring angiography.
Survival may be longer in patientswith chronic kidney disease afterCABG than PCI; however, the dataare inconclusive.
How should patients with treatedSIHD be followed?Follow-up visits should be scheduledperiodically according to the stabilityof clinical status and the establish-ment of consistent communicationwith patients and other physiciansinvolved in the care of the patient.Appointments should be scheduledevery 4 to 6 months during the firstyear of treatment and every 4 to 12months thereafter, as long as anginaremains stable and treatment is oth-erwise successful. Visits may be morefrequent after changes in medicalmanagement.
During each visit, obtain detailedinformation on angina (see theBox: Questions for Follow-up Visits). If symptoms increase in frequency or severity, inquire aboutthe exacerbating and alleviatingconditions. If the symptoms haveworsened or the patient has de-creased his or her physical activityto avoid angina, evaluate and treataccording to either the unstableangina or chronic stable anginaguideline. Changes in angina sever-ity or frequency may indicate wors-ening CAD, changes in comorbidconditions, or changes in social fac-tors (e.g., personal finance) thatmay affect disease severity.
Assess the patient for adherence totherapy, which may decline overtime, and adverse drug effects. At-tention to modifiable risk factors,such as smoking, at each visit in-creases the likelihood of successfulrisk reduction. Physicians shouldcontinue to encourage patients toengage in regular physical activityand recommend a balanced diet.
Laboratory evaluation should beused to monitor modifiable risk fac-tors. Perform a fasting lipid panel 6 to 8 weeks after initiating lipid-lowering therapy, then less frequentlyduring the first year of therapy.Measure creatine phosphokinase inpatients receiving statins who havemuscle weakness or pain, and moni-tor glycosylated hemoglobin at leastannually in patients with stable,
Questions for Follow-up VisitsHas the patient decreased his or her
level of physical activity since the lastvisit?
Has angina increased in frequency orbecome more severe since the lastvisit?
How successful has the patient been inmodifying risk factors and improvingknowledge about ischemic heartdisease?
Has the patient developed any newcomorbid illnesses or has the severityor treatment of known comorbidillnesses worsened angina?
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41. Braunwald E, MarkD, Jones RH. Unsta-ble angina: diagnosisand management.Clinical PracticeGuideline Number10. Rockville, MD:Agency for HealthCare Policy and Re-search and the Na-tional Heart, Lung,and Blood Institute,Public Health Serv-ice, U.S. Departmentof Health and Hu-man Services; 1994.
42. Diamond GA, For-rester JS. Analysis ofprobability as an aidin the clinical diag-nosis of coronary-ar-tery disease. N EnglJ Med. 1979;300:1350-8.
prove survival and symptoms, andpatient follow-up.
Guidelines on management of SIHDwere released in 2011 from the U.K.National Institute of Clinical Excel-lence. The guideline includes anemphasis on offering optimal drugtreatment for managing patientswith SIHD and revascularizationwhen symptoms are not controlledwith optimal drug treatment.
Some noteworthy trials on choosingbetween CABG and PCI were pub-lished since these guidelines werewritten. The Future Revasculariza-tion Evaluation in Patients with Diabetes Mellitus: Optimal Man-agement of Multivessel Disease(FREEDOM) trial found thatCABG resulted in lower rates ofmortality, MI and stroke comparedwith PCI (18.7% vs. 26.6% overall at5 years follow up) (38). Meanwhile,the FAME II trial showed that instable patients with a functionallysignificant coronary lesion, PCI re-duced the need for urgent revascu-larization more than medical therapyalone (the trial was stopped early).
What do professional organizationsrecommend with regard toprevention, screening, diagnosisand treatment of stable SIHD?The American College of Cardiol-ogy Foundation, American HeartAssociation, American College ofPhysicians, American Associationfor Thoracic Surgery, PreventiveCardiovascular Nurses Association,Society for Cardiovascular Angiog-raphy and Interventions, and Soci-ety of Thoracic Surgeons publisheda joint clinical guideline for the di-agnosis and management of pa-tients with SIHD in 2012.
Based on this clinical guideline, theAmerican College of Pyysicians pub-lished 28 recommendations address-ing the initial diagnosis of the patientwho might have SIHD, cardiac stresstesting to assess the risk for death orMI in SIHD, and coronary angiog-raphy for risk assessment. ACP alsopublished 48 recommendations onmanagement of SIHD that addressespatient education, management ofrisk factors, medical therapy to pre-vent MI and death and to relievesymptoms, revascularization to im-
TREATMENT... The main goals of treating patients with SIHD are to minimize thelikelihood of death while maximizing health and function. Risk factors like smok-ing, hyperlipidemia, diabetes, and high BP should be reduced as intensively as isreasonable with lifestyle modifications and medical therapy. Education is criticalto ensuring that the patient understands the underlying disease process, can makeinformed decisions about treatment options, and knows the warning signs andsymptoms of MI. All patients should have guideline-directed medical therapy toreduce the risk for mortality and relieve symptoms. Consider revascularization forpatients at high risk for mortality and for those with persistent symptoms despiteguideline-directed medical therapy. Follow-up should address angina, medicationuse, and modifiable cardiac risk factors, and follow-up testing should be directedby changes in symptoms.
CLINICAL BOTTOM LINE
Practice Improvement
of an intervening MI. Perform astress test only in patients with newor worsening symptoms that are notconsistent with unstable angina.
treated diabetes mellitus. Performechocardiography or radionuclideimaging only in patients with new orworsening heart failure or evidence
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Inthe
C linic
Tool KitIn the Clinic
Stable IschemicHeart Disease
ACP Smart Medicine Modulehttp://smartmedicine.acponline.org/content.aspx?gbosId=33&resultClick=3
Access the American College of Physicians Smart Medicine moduleson stable coronary heart disease and coronary artery disease inwomen. ACP Smart Medicine modules provide evidence-based,updated information on current diagnosis and treatment in anelectronic format designed for rapid access at the point of care.
Patient Informationwww.nlm.nih.gov/medlineplus/coronaryarterydisease.htmlwww.nlm.nih.gov/medlineplus/angina.htmlwww.nlm.nih.gov/medlineplus/ency/patientinstructions/000088.htmwww.nlm.nih.gov/medlineplus/ency/article/000198.htmInformation on coronary artery disease and on angina from the
National Institutes of Health MedlinePlus.www.nhlbi.nih.gov/health/health-topics/topics/angina/www.nhlbi.nih.gov/health-spanish/health-topics/temas/angina/Information for patients on angina, in English and in Spanish from
the National Heart, Lung, and Blood Institute.Clinical Guidelineshttp://eurheartj.oxfordjournals.org/content/34/38/2949.shortEvidence-based guidelines for the management of stable coronary
artery disease from the European Society of Cardiology in 2013.http://content.onlinejacc.org/article.aspx?articleid=1391404Evidence-based guidelines for the diagnosis and management of
patients with SIHD from the American College of CardiologyFoundation/American Heart Association Task Force on PracticeGuidelines, and the American College of Physicians, AmericanAssociation for Thoracic Surgery, Preventive Cardiovascular NursesAssociation, Society for Cardiovascular Angiography and Interventions,and Society of Thoracic Surgeons in 2012.
http://guidance.nice.org.uk/CG126Clinical guidelines on the management of stable angina from the
United Kingdom’s National Institute of Health and Care Excellencein 2011.
Diagnostic Tests and Criteriahttp://smartmedicine.acponline.org/content.aspx?gbosId=33&resultClick
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In the ClinicAnnals of Internal Medicine
Pati
ent
Info
rmat
ion
WHAT YOU SHOULDKNOW ABOUT STABLEISCHEMIC HEART DISEASE
What is a stable ischemic heartdisease?• Stable ischemic heart disease occurs due to poor blood
flow through the blood vessels in the heart.• During times of activity or stress when the heart
muscle works harder and needs more oxygen, it cancause pain or pressure in your chest.
• You may also feel angina in your shoulders, arms,neck, jaw, or back.
• The pain or pressure lasts for minutes, not secondsor hours, and goes away with rest or medication.
• Early diagnosis and treatment are important toreduce the risk for more serious complications.
• The most common cause is coronary heart disease,which results from the buildup of plaque in thearteries to your heart.
How is it diagnosed?• Your doctor will perform a thorough history and
physical examination and order blood tests to learnmore about your condition.
• You may undergo painless tests to show how yourheart is working, including an electrocardiogram,which measures the electrical activity of the heartmuscle, and an echocardiogram, which createsmoving pictures of how your heart is functioning.
• You may take a stress test, which provides informa-tion on how exercise affects angina symptoms andoverall heart functioning.
• Other tests may be needed, such as cardiac cathe-terization or coronary angiography to study thearteries and heart functioning.
How is it treated?• Your doctor may prescribe medications to help control
high blood pressure and blood cholesterol levels, to helpprevent heart attacks, and to help you live longer.
• A medication called nitroglycerin can reduce anginasymptoms when they occur.
• If your arteries are clogged, your doctor may performa nonsurgical procedure called percutaneouscoronary intervention to widen them.
• Blockages that cannot be treated with percutaneouscoronary intervention may need heart bypass surgery.
Can complications be prevented?• Stop smoking.• Make heart-healthy changes to your diet.• Practice stress reduction.• Exercise moderately on a regular basis.• Take your medications.
For More Informationwww.cardiosmart.org/Heart-Conditions/Coronary-Artery-Diseasewww.cardiosmart.org/Heart-Conditions/Anginawww.cardiosmart.org/Heart-Conditions/Angina/Questions-to-Ask-Your-DoctorPatient information on coronary artery disease and angina from
the American College of Cardiology, including questions to askyour doctor.
www.heart.org/HEARTORG/Conditions/HeartAttack/SymptomsDiagnosisofHeartAttack/Angina-Pectoris-Stable-Angina_UCM_437515_Article.jspwww.heart.org/HEARTORG/Conditions/HeartAttack/WarningSignsofaHeartAttack/Angina-in-Women-Can-Be-Different-Than-Men_UCM_448902_Article.jspInformation on stable angina and on angina in women from the
American Heart Association.
www.cdc.gov/heartdisease/www.cdc.gov/heartdisease/materials_for_patients.htmInformation about heart disease from the U.S. Centers for Disease
Control and Prevention, including educational materials forpatients.
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Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed at http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/
to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.
1. A 70-year-old woman is seen for anevaluation. Medical history is significantfor ischemic cardiomyopathy andhypertension. She had an implantablecardioverter-defibrillator placed 5 yearsago. She has good functional capacityand is able to walk 3 blocks withoutlimitations. Medications are lisinopril,carvedilol, aspirin, and pravastatin.
On physical examination, she is afebrile,blood pressure is 137/70 mm Hg, pulserate is 82/min, and respiration rate is18/min. BMI is 23. The remainder of theexamination is normal. Laboratorystudies reveal the following: HemoglobinA
Which of the following clinical measuresis most important to target in thispatient to reduce her risk for acardiovascular event?
A. Blood pressureB. Hemoglobin A
1c
C. LDL cholesterol levelD. Triglyceride level
2. A 67-year-old woman is evaluated for a3-week history of intermittent exertionalchest pain. She walks several days per
week. She has type 2 diabetes mellitusand hypertension. Her father had amyocardial infarction at age 54 years.Medications are aspirin, metformin,glyburide, and lisinopril.
On physical examination, she is afebrile,blood pressure is 128/90 mm Hg, pulserate is 83/min, and respiration rate is18/min. BMI is 35. Cardiac sounds aredistant but otherwise unremarkable,without extra sounds or murmur.
Figure 1 is the patient’s electrocar-diogram (ECG).
Which is the most appropriate diagnostictest to perform next?
A. Cardiovascular magnetic resonanceimaging with gadoliniumenhancement
3. A 68-year-old woman is evaluated duringa routine examination. She went throughmenopause 16 years ago. She is obese.Family history is significant for apaternal aunt with ovarian cancer at age64 years. She takes no medications.
Blood pressure is 148/90 mm Hg, pulserate is 83/min, and respiration rate is
18/min. BMI is 35. Waist measurement is100 cm (39.3 in).
Which disease poses the greatest risk fordeath in this patient?
A. Breast cancerB. Coronary artery diseaseC. Diabetes mellitusD. Ovarian cancer
4. A 35-year-old woman is evaluated during afollow-up examination. She has hadrecurrent episodes of presyncope andsyncope over the past few months. Shecontinues to have an episode every 3 to 4weeks, with no discernible pattern ortrigger. She reports becoming light-headedand feeling faint, without other associatedsymptoms, followed by transient loss ofconsciousness for several seconds followedby spontaneous recovery without residualsymptoms. On previous evaluation, anelectrocardiogram (ECG) andechocardiogram were normal. Results of24-hour continuous ambulatory ECGmonitoring were unremarkable, and acardiac event recorder showed noarrhythmia associated with presyncopalsymptoms. History is significant for anxietyand intermittent insomnia; the patienttakes no medications for these conditions.There is no history of prior head trauma.She does not use drugs or alcohol.
On physical examination, temperature isnormal. Blood pressure is 122/68 mm Hgand pulse rate is 72/min while supine.After three minutes of standing, bloodpressure is 112/84 mm Hg and pulse rateis 88/min, without reproduction ofsyncope or symptoms. The remainder ofthe examination is normal. Serumelectrolytes, kidney function, and thyroidfunction studies are normal.
Which is the most appropriate next stepin the evaluation of this patient?
