Preventing Atherosclerotic Vascular Disease

Recommendations for Antiviral Treatment of H1N1

• For patients with confirmed or strongly suspected infection with influenza pandemic (H1N1) 2009, when antiviral medications for influenza are available, specific recommendations regarding use of antivirals for treatment of pandemic (H1N1) 2009 influenza virus infection are as follows:

• Oseltamivir should be prescribed, and treatment started as soon as possible, for patients with severe or progressive clinical illness (strong recommendation, low-quality evidence). Depending on clinical response, higher doses of up to 150 mg twice daily and longer duration of treatment may be indicated. This recommendation is intended for all patient groups, including pregnant women, neonates, and children younger than 5 years of age.

• Zanamivir is indicated for patients with severe or progressive clinical illness when oseltamivir is not available or not possible to use, or when the virus is resistant to oseltamivir but known or likely to be susceptible to zanamivir (strong recommendation, very low quality evidence).

• Antiviral treatment is not required in patients not in at-risk groups who have uncomplicated illness caused by confirmed or strongly suspected influenza virus infection (weak recommendation, low-quality evidence). Patients considered to be at risk are infants and children younger than 5 years of age; adults older than 65 years of age; nursing home residents; pregnant women; patients with chronic comorbid disease including cardiovascular, respiratory, or liver disease and diabetes; and immunosuppressed patients because of malignancy, HIV infection, or other diseases.

• Oseltamivir or zanamivir treatment should be started as soon as possible after the onset of illness in patients in at-risk groups who have uncomplicated illness caused by influenza virus infection (strong recommendation, very low quality evidence).

Recommendations for Chemoprophylaxis of H1N1

• Specific recommendations regarding the use of antivirals for chemoprophylaxis of pandemic (H1N1) 2009 influenza virus infection are as follows:

• When risk for human-to-human transmission of influenza is high or low, and the probability of complications of infection is high, either because of the influenza strain or because of the baseline risk of the exposed group, use of oseltamivir or zanamivir may be considered as postexposure chemoprophylaxis for the affected community or group, for individuals in at-risk groups, or for healthcare workers (weak recommendation, moderate-quality evidence).

• Individuals in at-risk groups or healthcare personnel need not be offered antiviral chemoprophylaxis if the likelihood of complications of infection is low. This recommendation should be applied independent of risk for human-to-human transmission (weak recommendation, low-quality evidence).

• For treatment of mild to moderate uncomplicated clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities, patients in at-risk groups should be treated with zanamivir or oseltamivir plus M2 inhibitor (noting that amantadine should not be used in pregnant women). Otherwise-healthy patients with this presentation need not be treated.

• When the clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities is severe or progressive, all patients should be treated with oseltamivir plus M2 inhibitor, or zanamivir.

• For treatment of mild to moderate uncomplicated clinical presentation of infection with sporadic zoonotic influenza A viruses including H5N1, the at-risk population should be treated with oseltamivir or zanamivir, and the otherwise-healthy population with oseltamivir. All patients, regardless of risk status, with severe or progressive presentation of infection with sporadic zoonotic influenza A viruses including H5N1 should be treated with oseltamivir plus an M2 inhibitor.

Smoking Cessation from FP Audio Digest 362

• 20% of the US population smokes cigarettes

• At least 70% of individuals who smoke see a physician each year.

• Approximately 70% of individuals who smoke want to quite

• Only 25 to 33% report receiving guidance or follow-up related to smoking cessation.

Health Behavior: Smoking Cessation

• A 3 minute intervention can increase the likelihood of quitting

• A 4 to 30 minute intervention can almost double quite rates

• A 31 to 90 minute intervention can almost double quit rates

• Rates are compared with no discussion or tobacco use.

Helping patients quit

• The 2008 Treating Tobacco Use and Dependence guidelines encourage the use of the 5 A’s

• Ask, ask every patient at every visit about tobacco use status.

• Advise, every tobacco user should be advised to quit. Tell them you are willing to help them quit. Quitting tobacco is the most important thing you can do to protect you health. Even light smoking is dangerous. Whenever you’re ready to quit let me know and we will do everything we can to help you to be successful.

Continuing the 5 A’s• Assess• Try to determine patient willingness to quite• Assist• Target the habits and behaviors, thoughts and emotions and

physiologic factors that contribute to tobacco use.• Establish a quit plan with a time and date.• Prepare for a quit date, by not buying tobacco in bulk and make

clean areas in which tobacco is not to be used. Smoke outside. It will reduce the effects of tobacco on any of those who are exposed to the smoke.

• Eliminate materials associated with tobacco use like lighters and ashtrays.

Assist

• Ask patients to think about past quit experiences• Identify a support system.• Determine if avoiding certain individuals will help in quitting cigarettes• Ask others to help you quite, also known as quite buddies• Encourage others in household to quite smoking.• Behavioral techniques.• Nicotine fading• Gradually decreasing the amount of nicotine consuming over time. Tapering the frequency of tobacco use over time. Switching to a brand of tobacco that contains less nicotine.

Assist• Aversive tobacco use• Rapid consumption of tobacco, intended • to make the last experience with • tobacco unpleasant to decrease the • likelihood of relapse.• Brand switching• Consumption of a different brand of tobacco • that is stronger to make the last experience• with tobacco unpleasant to decrease relapse• Aversive or rapid smoking techniques increase the likelihood of

success by 1.5 to 2 times.•

Pharmacotherapy• 2008 treating tobacco use and dependence guidelines recommend seven

first-line treatments• Rive nicotine replacement therapies• Transdermal nicotine• Nicotine gum• Nicotine inhaler• Nicotine lozenge• Nicotine nasal spray• Two non-nicotine replacement therapies which include Bupropion SR

(Zyban) and Varenicline (Chantix)• Most effective treatment combines behavioral counseling and

pharmacotherapy • Every individual who smokes should be offered drug treatment to assist

with quitting.

Assist• Help the patient develop skill to manage challenges after the

quit date.• Total abstinence is the goal• Main reasons for relapse are 1. Stress 2. Withdrawal

symptoms 3. Cravings• Determine what to do in response to tobacco use urge.• 4 A’s• Avoid situations associated with tobacco use• Alter the habits• Alternative include gum, mints, and cinnamon sticks. • Activity, increasing it helps with everything

Assist• Encourage patients to consider themselves individuals who

do not smoke• When they encounter increased urges to use tobacco have

them ask themselves “What would a nontobacco user do?”• Ask patients what they will do when they believe they

must use tobacco.• Briefly discuss methods to challenge beliefs that they must

use tobacco.• I would like to have a cigarette but I don’t need or I don’t

have to have one now”.• Distract themselves with another activity.

Assist• Stress management• Determine current methods beside tobacco use to manage

stress.• Brief relaxation techniques.• Cognitive strategies.• Increased physical activity.• Lapses and relapses• Most lapses occur within the first 5 to 10 days after quitting• 90% of lapses lead to relapses• Meeting with a patient within the first week of the quit date

may help decrease the likelihood of lapse

Assist• Quit lines• http://www.smokefree.gov.• 1-800-QUITNOW (1-800-784-8669).• 1-800-NOBUTTS (1-800-662-8887).• Arrange• Praise successful quit attempts• Review benefits of quitting• Discuss problems associated with quitting• If a patient experiences a lapse or relapse• Discuss recommitting to quit effort• Set a new quit date

A man, 48 yr of age, presents with acute chest pain.

Evaluation reveals evidence of acute myocardial ischemia and existing cardiovascular disease. What target level of low-density lipoprotein cholesterol (LDL-C) is

recommended? A) <130 mg/dL B) <100 mg/dL C) <70 mg/dL D) <40 mg/dL

Answer

•  C) <70 mg/dL

Which of the following statins are metabolized via the cytochrome

P450 3A4 system?AtorvastatinFluvastatinLovastatinPravastatin

RosuvastatinSimvastatin

 A) 1,6 B) 1,3,6 C) 4,5

 D) 2,4,5

Answer

1. Atorvastatin2. Lovastatin3. Simvastatin•

  B) 1,3,6

Which of the following statins has the highest

relative efficacy? A) Atorvastatin B) Pravastatin

 C) Rosuvastatin D) Simvastatin

Answer

•  C) Rosuvastatin

Which of the following statements about statin-associated myalgia is true?

 A) It is responsible for the increased rate of discontinuation that occurs with higher

doses B) Biopsy reveals pathologic changes in

muscle tissue in some patients with myalgia

 C) Discontinuation of the statin is recommended only if creatine kinase

levels are elevated D) There is good evidence that supplementation with coenzyme

Q10reduces risk for myalgia

Answer

•  B) Biopsy reveals pathologic changes in muscle tissue in some patients with myalgia

The goal for non-high-density lipoprotein

cholesterol (non-HDL-C) is _______ higher than the

goal for LDL-C. A) 30 mg/dL B) 40 mg/dL C) 50 mg/dL D) 60 mg/dL

Answer

•  A) 30 mg/dL

Raising levels of HDL-C without changing other

lipid parameters is independently associated

with reduced cardiovascular (CV) risk.

 A) True B) False

Answer

•  B) False

Niacin monotherapy has been associated with

significantly decreased risks for coronary death and nonfatal myocardial

infarction. A) True B) False

Answer

•  A) True

 All the following statements about triglyceride levels are true, except: A) Independently predictive of CV

disease B) Higher predictive value among

men than among women C) Elevated levels associated with

production of small, dense LDL particles

 D) Significantly decreased with niacin therapy

Answer

•  B) Higher predictive value among men than among women

 The level of non-HDL-C: A) Can be measured easily and

inexpensively B) Requires fasting for accurate

measurement C) Is a poorer predictor of

atherosclerosis than level of LDL-C

 D) Is predictive of risk in adults but not in children or

adolescents

Answer

• A) Can be measured easily and inexpensively

Which of the following drug combinations has/have been shown

to be significantly more effective than statin monotherapy at lowering

CV risk?Bile acid resin plus statinBile acid resin plus niacin

Statin plus fibrateStatin plus antioxidants

 A) 1 B) 1,2 C) 1,3 D) 1,4

Answer

1. Bile acid resin plus statin2. Bile acid resin plus niacin•

  B) 1,2

Trends

• coronary heart disease (CHD) remains leading cause of death in United States

• prevalence expected to increase• Some improvements in trends (eg, total

cholesterol levels), but 48% of adults have total cholesterol levels above 200 mg/dL

• 33% have elevated levels of low-density lipoprotein cholesterol (LDLC)

• 17% have low levels of high-density lipoprotein cholesterol (HDL-C)

Risk assessment:• Framingham risk calculator—calculates risk• based on levels of LDL-C and HDL-C, systolic blood pressure,

smoking, age, and gender• estimates 10-yr risk for nonfatal myocardial infarction (MI) or

fatal CHD• Coronary equivalents—diabetes; abdominal aortic aneurysm

greater than 3.5 cm; peripheral vascular disease; carotid disease or history of transient

• ischemic attack (TIA)• Lower LDL targets recommended for patients with coronary

equivalents• identifying at-risk patients—important to identify patients with

multiple risk factors who have not yet had cardiac event• risk calculators available online• document calculated risk and discuss implications with patients

LDL goals• target less than 100 mg/dL for high-risk patients• target less than 70 mg/dL recommended if patient has

cardiovascular (CV) disease and multiple risk factors (eg, diabetes, metabolic syndrome, acute coronary syndrome [ACS])

• best evidence for patients with CV disease and ACS• for patients with ACS or unstable angina, initiate lipid-

lowering therapy within 24 hr or before discharge, unless contraindicated

• management— lifestyle interventions; statins as first-line medical therapy

• adjunctive therapies include bile acid resins, ezetimibe, and niacin

Statins• effects—LDL-C level lowered; endothelial function restored;• decreased level of high-sensitivity C-reactive protein (hsCRP)• fewer ischemic episodes on exercise stress tests• plaques stabilized• decreased risk for cardiac events• Decreased mortality rate options—6 agents available;

potencies,• pharmacokinetics, drug interactions, and metabolic pathways

differ• generic simvastatin available; atorvastatin,• lovastatin, and simvastatin metabolized via cytochrome P450

3A4 system (interact with azole antifungal agents, HIV medications, or macrolide antibiotics

• decrease dose, withhold statin, or switch to other statin with no interaction)

Statins• Efficacy: strategies for increasing efficacy—double dose (results

in additional 6% reduction in level of LDL-C)• Switch to more potent statin• add adjunctive therapy (eg, ezetimibe, bile acid resin)• relative efficacies—trial showed 20 mg rosuvastatin produced

reduction in LDL-C similar to that seen with 80 mg atorvastatin• measuring markers of risk—clinical trial showed combination• agent (simvastatin plus ezetimibe [Vytorin]) associated with

additional reductions in levels of LDL-C and hsCRP (compared to simvastatin alone)

• but no additional improvement in carotid intima-medial thickness

• finding led to concernabout extrapolating effects on markers of risk (eg, hsCRP) to CV outcomes (new study will analyze effect on CV end points)

Statins• Safety and tolerability: although generally safe and well-tolerated,• over-the-counter formulations not recommended by• monitoring important• also important to know when (and why) patients discontinue taking statins• Trials comparing different statins and different dosing regimens• conclude that lowering LDL-C levels to less than 40 mg/dL improves

outcomes without compromising safety• Higher doses associated with higher rate of discontinuation (related mostly

to elevated liver enzymes, not to increased myalgias)• hepatotoxicity—generally low• risk increases with alcohol use and drug interactions• myalgia—relatively low incidence, but one study showed pathologic

changes on muscle biopsy in some patients• consider discontinuing or switching to different statin, even if creatine

kinase level not elevated• most trial data do not support supplementation with agents like CoEnzyme

Q, but some patients report improvement with 100 to 200 mg/day

High-sensitivity CRP

• independent marker of CV risk• Optional component of coronary risk

assessment in adults without known CV disease

• most useful for patients at intermediate risk• elevated CRP (1-3 mg/L) may be reason to

decrease LDL goal to less than 100 mg/dL• Framingham Heart Study identified hsCRP as

predictor of CV disease

Primary prevention• Justification for the Use of Statins in Prevention: an Intervention

Trial Evaluating Rosuvastatin (JUPITER)• double blind, randomized trial comparing 20mg rosuvastatin to

placebo for primary prevention of CV events among adults with LDL-C less than 130 mg/dL and hsCRP greater than 2 mg/L, but no history of CV disease or diabetes

• data monitoring board stopped study early because of benefit seen with active treatment

• treatment associated with improved LDL, hsCRP, and all CV outcomes, except for hospitalization for unstable angina

• clinical implications—in JUPITER, hsCRP measured as marker of risk, not as means of guiding therapy

• data support expanding use of statins for primary prevention• considerations include potential benefits, long-term safety, and

cost-effectiveness

Risk-based management

• Heart Protection Study (HPS) 20,000 participants, 40 to 80 yr of age, with high CV risk, randomized to 40 mg simvastatin or placebo

• simvastatin associated with 34% reduction in mortality and CV events, regardless of baseline LDL-C (including patients with baseline

• LDL-C 80 mg/dL)• results suggest that overall CV risk (instead• of LDL-C level alone) should guide therapy• American Diabetes Association recommendations—

statins indicated for diabetic patients 40 yr of age (unless contraindication present), regardless of LDL-C level

Non–HDL-C• clinical trials of statin therapy show that residual CV risk exists after LDL-C

target met• residual risk associated with other atherogenic lipoproteins• calculating non–HDL-C—subtract HDL-C from total cholesterol• goal—30 mg/dL higher than goal for LDL-C• clinical relevance—correlates closely with obesity, visceral adiposity, and

metabolic syndrome• Predicts CV risk more strongly than does LDL-C• includes LDL-C, intermediate-density lipoproteins, chylomicrons and

chylomicron remnants• in Framingham Heart Study, little association found between level of LDL-C and

risk for CHD, after controlling for level of HDL-C• but HDL-C strongly associated with risk, even after controlling for level of LDL-C• Strong Heart Study—non–HDL-C predicted CV risk as well as LDL-C among

American Indian men and women• ratio of total cholesterol to HDL-C also good predictor (target ratio less than 3.5)• guidelines—non–HDL-C recommended as secondary target of therapy for

patients with triglyceride levels 200 mg/dL and above.

Raising HDL-C• agents—nicotinic acid (niacin; considered most

effective agent)• Fibrates• fish oils• benefits—low level of HDL-C associated with

increased risk for CV events• but no good evidence that raising level

(independent of other changes in lipid profile) improves outcomes

• Except Helsinki heart study 1987 with Gemfibricil• Every 1% rise in HDL-C had 2% reduction in

coronary events

Beyond statins

• niacin—Coronary Drug Project showed monotherapy associated with significantly decreased risks for coronary death and nonfatal MI (compared to placebo)

• gemfibrozil—monotherapy shown beneficial for secondary prevention in population with underlying CHD

• take-home point—patients unable to take statins have options including

• bile acid resins, ezetimibe, niacin, and fibrates

Combination therapies• insufficient evidence that specific combinations result in improved risk reduction• niacin, fibrates, and omega-3 fatty acids suggested as possible combination therapies• statin plus niacin—HDL-Atherosclerosis Treatment Study (HATS)• 160 patients with known coronary• disease, low level of HDL-C, and LDL-C less than 145 mg/dL at baseline baseline• randomized to simvastatin plus niacin, antioxidants alone• combination of simvastatin, niacin, and antioxidants, or placebo;• simvastatin plus niacin associated with improvements in lipid profiles and significant

reductions in risks for coronary death, MI, stroke, and revascularization and in regression of coronary stenosis

• no benefit seen with antioxidants• Adding antioxidants appeared to reduce efficacy of combination therapy• larger study (in progress) comparing simvastatin monotherapy• with simvastatin plus niacin• statin plus fibrate—no clinical trial has compared combination to statin monotherapy• gemfibrozil should not be combined with higher doses of statins, because of increased risk

for rhabdomyolysis• Fenofibrate safe to combine with statins• arm of Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (in progress)• will compare simvastatin alone to simvastatin plus fenofibrate in patients with type 2

diabetes

Questions and answers

• statins for primary prevention in premenopausal women• decision to treat based on CV risk generally, • premenopausal women have low risk• Statins recommended for women with underlying CV disease, diabetes, or others with

high risk• statins as effective in women as in men• statins and risk for diabetes—trial showed treatment with rosuvastatin increased risk for

new-onset diabetes but decreased mortality• significance unclear• myalgias—discontinue statin• measure creatine kinase (if normal, consider other causes)• myalgia should resolve in 1 to 2 wk after discontinuation (if not, consider other causes)• Augmentative medications (eg, ezetimibe) also may cause myalgias• Elevated liver enzymes—reduce dose or discontinue statin if aspartate aminotransferase

or alanine aminotransferase 3 times upper limit of normal (ULN)• moderate elevations (eg, up to 4 times ULN) of creatine kinase acceptable as long as

patient remains asymptomatic• fish oil—good adjunctive therapy• Evidence for use in patients with underlying CV disease• for primary prevention, benefit unclear

Beyond LDL Cholesterol

• Dyslipidemia and CV risk: statin therapy effectively reduces level of LDL-C

• patients with high triglycerides and low levels of HDL-C have residual risk for atherosclerosis; important to address all aspects of dyslipidemia

• triglycerides—independent predictor of CV disease• Framingham study found triglyceride level and HDL-C level

more predictive in women than men• another study showed that, among individuals with

premature heart disease and family history of CV disease, triglyceride level associated with increased risk (11-fold higher when 500 mg/dL vs 100 mg/dL

• 17-fold higher when triglyceride level 300 mg/dL and HDL-C level 30 mg/dL)

Lipoprotein interactions

• when triglycerides elevated, cells produce abnormal forms of cholesterol (especially in patients with abdominal obesity)

• triglycerides transiently inserted into LDL particle, then removed by cholesterol-ester transfer protein, creating small, dense LDLs

• these small LDLs oxidize easily and penetrate arteries more rapidly than larger LDL particles

• standard lipid profile does not detect small LDLs• Situation common among patients with abdominal obesity, high

triglycerides, and low level of HDL• individuals with low levels of triglycerides do not produce small

LDLs• production of small LDLs substantially increases when triglyceride

level reaches 80 to 100 mg/dL• by 150 mg/dL, almost all LDL particles are small LDLs• guidelines list triglyceride level of 150 mg/dL as risk factor (cutoff

may change to 100 mg/dL in next version of guidelines)

Total number of LDL particles• best predictor of CV risk

• tests—Vertical Auto Profile (VAP) test and Berkeley Heart- Lab test measure size, but not number of particles

• LipoProfile nuclear magnetic resonance (NMR) spectroscopy measures number and size of lipoprotein particles

• Individuals who produce small LDL particles also tend to produce small HDL particles, which have impaired function (less protective than normal-sized HDL particles)

• target—10 times target level of LDL (eg, if LDL goal 100 mg/dL

• total particle number should be 1000)

Non–HDL-cholesterol• high consumption of carbohydrates results in

production of inflammatory, proatherogenic triglyceride- rich particles (eg, very low-density lipoproteins [VLDL], intermediate-density lipoproteins [IDL])

• measuring non– HLD-C—subtract HDL-C from total cholesterol

• Inexpensive test• advantages—best lipid parameter for predicting

atherosclerosis in adults, adolescents, and children• Fasting not required (convenient; reflects “real life”

postprandial status)• high correlation with visceral adiposity

HDL-cholesterol

• low levels associated with increased risk for

• CHD, especially among women; effects—participates in reverse

• cholesterol transport; reduces oxidation; decreases risk

• for thrombosis; improves arterial function; inhibits inflammatory

• molecules

Fibrates

• gemfibrozil—lowers triglycerides and raises level of HDL-C• has little effect on LDL-C• treatment associated with 70% reduction in relative risk for coronary

events among patients with high levels of triglycerides (above 200 mg/dL) and low levels of HDL-C

• little benefit seen among those with lower levels of triglycerides• study in patients with CV disease, LDL-C above 130 mg/dL,

triglycerides above 150 mg/dL, and• HDL-C less than 40 mg/dL showed monotherapy resulted in 8%

reduction in absolute risk (for vascular events over 5 yr) among patients with diabetes and 5% absolute risk reduction among

• patients without diabetes (similar to or better than that associated with statin therapy in patients with CHD)

• fenofibrate—study found no significant differences in primary end points between active-treatment and control groups

• patient population poorly selected (ie, included patients not expected to benefit)

Niacin

• Niacin vitamin B3• long-term clinical trials (eg, Coronary Drug

Project) showed treatment associated wit decreased rates of CV events, coronary mortality, and total mortality

• Aggressive combination therapy may result in regression of atherosclerosis

• recommendations for improving tolerance—take aspirin before taking niacin

• take with food and water

Combination therapy• appropriate for high-risk patients with• More than 1 component of dyslipidemia• combination therapy with bile acid resin

(colestipol) plus niacin or statin results in significantly greater risk reduction (total mortality and CV events) compared to statin monotherapy

• aggressive therapy reduces 10-yr mortality rate by 18%

• if combining statin with fibrate, use fenofibrate

Statins for Primary Prevention of Cardiovascular Disease

• Statin users were less likely to experience major adverse coronary or cerebrovascular events.

• Statins clearly confer substantial benefit in people with established cardiovascular (CV) disease (secondary prevention); however, the magnitude of benefit in people without CV disease (primary prevention) is less clear. In this meta-analysis of 10 randomized controlled trials that involved 70,000 patients, investigators assessed the effects of statins in people without CV disease but with CV risk factors.

• Participants (mean age, 63; 34% women) were followed for an average of 4.1 years. Compared with participants in the statin group, significantly more participants in the control group died (5.1% vs. 5.7%; odds ratio, 0.88), had major adverse coronary events (4.1% vs. 5.4%; OR, 0.70), or had major adverse cerebrovascular events (1.9% vs. 2.3%; OR, 0.81). Also, no significant differences in treatment benefits were noted between men and women, younger and older participants, and those with and without diabetes. Notably, statin use was not associated with excess risk for cancer.

• Comment: In this meta-analysis, statins significantly lowered risks for death, major adverse coronary events, and major adverse cerebrovascular events in patients without established CV disease but with CV risk factors. These results, however, should be interpreted with caution: Whereas the relative risk reductions are impressive, the absolute risk reductions are small. The authors acknowledge that "the absolute treatment benefit . . . would certainly be less than 1%, and significant numbers" of patients (i.e.,  100) would need to be treated for 4 years to prevent 1 adverse CV event.

Beta-Blockers in Heart Failure Patients with Preserved Systolic Function

• Findings from a SENIORS substudy suggest that the benefits of beta blockade extend to patients without LVSD.• Despite several trials, effective evidence-based therapies for patients with heart failure and preserved LV systolic

function remain frustratingly elusive. Investigators for the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure (SENIORS) assessed the efficacy of the vasodilating beta-1 receptor blocker nebivolol in adults aged  70 with heart failure and a broad range of LV systolic function. In the complete SENIORS cohort, nebivolol treatment resulted in a marginally statistically significant reduction in the risk for death or cardiovascular hospitalization (hazard ratio, 0.86). In this prespecified substudy, the authors compared the results in patients with LV systolic dysfunction (LVSD) with those in patients with preserved LV systolic function.

• Of 2111 SENIORS patients, 752 had preserved LV systolic function (LV ejection fraction >35%), 37% were women, 69% had a history of coronary artery disease, and 82% were taking ACE inhibitors. Treatment effects did not differ significantly between the patients with preserved systolic function and those with LVSD. The results were similar when adjusted for baseline heart rate and change in blood pressure. Adverse events were not reported.

• Comment: The SENIORS trial is an important study because the enrolled population reflects the general population with heart failure better than previous trial populations. Although the substudy results suggest that nebivolol benefits patients across a wide range of LV systolic function, it would be premature to change practice on this basis. The authors appropriately concede that further study is warranted before we can firmly conclude that beta-blockers are particularly useful in patients with preserved systolic function. The ongoing Japanese Diastolic Heart Failure study of the effects of carvedilol in 800 patients with preserved LV systolic function should provide more-robust dat

• CITATION(S):• van Veldhuisen DJ et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved

left ventricular ejection fraction: Data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol 2009 Jun 9; 53:2150.

Healthy Lifestyle Blunts Risks for Heart Failure, Hypertension

• "Healthy lifestyle is associated with reduced risk of both hypertension and heart failure," an editorialist concludes from two prospective JAMA studies.

• One study examined the risk for heart failure in some 21,000 male physicians followed for over 20 years. The more the subjects practiced six healthy lifestyle habits, the less likely they were to develop heart failure during follow-up. The healthy habits included: keeping a normal weight, not smoking, exercising regularly, drinking moderately, eating breakfast cereals, and consuming fruits and vegetables. Heart failure risk was 21% with adherence to none of the six, and 10% with adherence to four or more.

• Similarly, a study following some 84,000 female nurses for 14 years revealed that greater adherence to a number of lifestyle habits was associated with a lower incidence of hypertension. The factors were: BMI under 25, regular exercise, DASH-diet adherence, moderate drinking, infrequent use of nonnarcotic analgesics, and folic acid supplementation. The difference in incidence between those adhering to all six habits versus those adhering to none was calculated to be about 8 cases per 1000 person-years.

Suggested Reading• Brown BG et al: Simvastatin and niacin, antioxidant vitamins, or• the combination for the prevention of coronary disease. N Engl J• Med 345:1583, 2001; Grundy SM et al: Effectiveness and tolerability• of simvastatin plus fenofibrate for combined hyperlipidemia• (the SAFARI trial). Am J Cardiol 95:462, 2005; Heart Protection• Study Collaborative Group: MRC/BHF Heart Protection Study of• cholesterol lowering with simvastatin in 20,536 high-risk individuals:• a randomised placebo-controlled trial. Lancet 360:7, 2002;• Hopkins PN et al: Plasma triglycerides and type III hyperlipidemia• are independently associated with premature familial coronary artery• disease. J Am Coll Cardiol 45:1003, 2005; Jones PH, Davidson• MH: Reporting rate of rhabdomyolysis with fenofibrate + statin• versus gemfibrozil + any statin. Am J Cardiol 95:120, 2005; Jones• PH et al: Comparison of the efficacy and safety of rosuvastatin versus• atorvastatin, simvastatin, and pravastatin across doses (STELLAR• Trial). Am J Cardiol 92:152, 2003; Kastelein JJ et al:• Simvastatin with or without ezetimibe in familial hypercholesterolemia.• N Engl J Med 358:1431, 2008; Koren MJ et al: Impact of• high-dose atorvastatin in coronary heart disease patients age 65 to• 78 years. Clin Cardiol 32:256, 2009; Marcoff L, Thompson PD:• The role of coenzyme Q10 in statin-associated myopathy: a systematic• review. J Am Coll Cardiol 49:2231, 2007; National Cholesterol• Education Program (NCEP) Expert Panel on Detection,• Evaluation, and Treatment of High Blood Cholesterol in Adults:• Third report of the NCEP Expert Panel on Detection, Evaluation,• and Treatment of High Blood Cholesterol in Adults final report. Circulation• 106:3143, 2002; Ridker PM et al: Baseline characteristics• of participants in the JUPITER trial. Am J Cardiol 100:1659, 2007;• Rubins HB et al: Gemfibrozil for the secondary prevention of coronary• heart disease in men with low levels of high-density lipoprotein• cholesterol. N Engl J Med 341:410, 1999.

Cardiovascular (CV) disease (CVD):

• Cardiovascular (CV) disease (CVD): number one cause of death in United States

• 90% of risk attributed to known risk factors; • risk factors include positive family history,

elevated blood pressure (BP), smoking, and dyslipidemia;

• of these, dyslipidemia management has most room for improvement

• (only 18%-30% of patients achieve recommended levels)

Calculating risk:

Calculating risk: Framingham risk calculator calculates 10-yr risk for coronary death or myocardial infarction (MI)based on age, sex, low-density lipoprotein (LDL) and highdensitylipoprotein (HDL) levels, smoking history, and BP;

shortcomings—lifespan has increased since original

Framingham study (no data from patients >79 yr of age);

calculator does not factor in family history (important considerationin risk assessment)

LDL Targets

LDL targets: based on risk category; LDL <100 mg/dL considered optimal, because atherogenesis arrests at this level;in Americans, average LDL 136 mg/dL, but treatment not recommended for all patients with LDL >100 mg/dL (problems include cost and adverse effects); guidelines consider risk- and cost-benefit ratios; recommendation of LDL <100mg/dL reserved for patients at high risk (ie, with established disease)

Therapeutic lifestyle changes:

Therapeutic lifestyle changes: nutritional medicine consultation recommended (when possible) for thorough nutritional counseling; diet—increase soluble fiber (good sources include beans, pears, apples, and oats); reduce and maintain body mass index (BMI) <25 (further reduction in BMI not associated with additional reduction in LDL); exercise—increase physical activity to ≥2000 steps/day; encourage walking during normal daily activities; consider formal prescription for exercise

Which of the following therapeutic lifestyle interventions are associated with

decreased levels of low-density lipoprotein (LDL)?

1. Increasing intake of soluble fiber 2. Increasing intake of insoluble fiber

3. Aerobic exercise 4. Weight loss to decrease body mass

index (BMI) to <25 5. Weight loss to decrease BMI to <22

A) 1,2,3,4B) 1,3,5C) 2,3,4D) 2,3,5

Answer

A. 1, 2, 3, 4

Medical therapyMedical therapy: recommended for secondary prevention;

acceptable for primary prevention in some cases, but therapeutic lifestyle strategies should be attempted first;

Medical Letter provides unbiased information (not supported by advertising) about medications; treatment guidelines for dyslipidemia published in February 2008; resins—effective at lowering LDL; associated with abdominal adverse effects; niacin—inexpensive; improves all aspects of lipid profile; may cause flushing and dyspepsia (most patients can tolerate dose of 500 mg); fibrates—fenofibrate and gemfibrozil; only fenofibrate

should be combined with statin (gemfibrozil plus statin increases risk for rhabdomyolysis); combination therapies—ezetimibe may be combined with other therapies (eg, simvastatin); lovastatin plus niacin; fish oil— prescription formulation (Lovasa) available; patients report fewer adverse effects (eg, belching, odor), compared to over-the-counter (OTC) formulations

StatinsStatins: all have anti-inflammatory effects; potency

increases when given at night because serum level peaks when cholesterol production peaks (1:00 to 3:00 AM); safety—adverse effects rare; simvastatin available OTC in United Kingdom since 2004; large meta-analysis found low risk overall; adverse effects include elevated transaminases (reversible), rhabdomyolysis (very rare), and myalgias (uncommon in clinical trials; may be more common in practice); options—atorvastatin; lovastatin (must take with food); pravastatin (dual pathways of elimination; lowest rate of adverse effects; only statin approved for aviators); simvastatin (most data); fluvastatin (least potent); rosuvastatin (high potency; may increase risk for reduced creatinine clearance in Asian subpopulations)

Statins

• 40% LDL reduction with

• 40 mg Simvastatin

• 20 mg Atorvastatin

• 80 mg Lovastatin and Pravastatin

• 5 mg Rusevastatin

• Fluvastatin can’t get you to 40% reduction maybe 35% reduction with 80 mg.

What is the rule of 7’s with statins?

This is a need to know, PERIOD!

Answer

If you double a dose of a statin you will get at most a 7% more reduction in the LDL level

All the following agents may be combined safely

with statins, except:A) FenofibrateB) GemfibrozilC) Ezetimibe

D) Niacin

Answer

B) Gemfibrozil

Lowering LDL targetsLowering LDL targets: Pravastatin or Atorvastatin

Evaluation and Infection Therapy (PROVE-IT) showed that atorvastatin lowered LDL levels further than pravastatin (average, 62 mg/dL vs 95 mg/dL) and was associated with 16% fewer events and 28% fewer deaths among patients with established disease; reversing atherogenesis—although atherogenesis arrests at LDL <100 mg/dL, it reverses at LDL <80 mg/dL in animal studies; updated guidelines—consider goal of LDL <70 mg/dL for patients at very high risk (note, basic research shows reversal of atherogenesis at LDL <80 mg/dL, but participants in clinical trials had levels <70 mg/dL); set goal of LDL <100 mg/dL for patients at high risk

Which of the following statements about statins is true?

A) Only simvastatin and pravastatin have anti-inflammatory effects

B) Potency increases when taken at night

C) Associated adverse effects render statins intolerable to ≈10% of

patientsD) Rosuvastatin is associated with the lowest rate of adverse effects

Answer

B) Potency increases when taken at night

Animal studies have shown that atherogenesis

reverses at LDL levels:A) <100 mg/dLB) <80 mg/dLC) <70 mg/dLD) Reversal of

atherogenesis has not been demonstrated at any

level of LDL

Answer

B) <80 mg/dL

Beyond LDL: Other Serum Markers for Risk Assessment

Traditional risk factors: 90% of risk for CVD determined by hypertension, smoking history, family history, and LDL; however, 50% of patients who have CV events have normal LDL levels; other markers may help predict events in patients at intermediate risk

Atherosclerosis: requires “raw materials” (excess lipids) and “machinery” (inflammation); serum markers must measure one of these

Candidate markers: HDL; triglycerides; apolipoprotein A-1 (apo A-1); apolipoprotein B (apo B); lipoprotein(a); highsensitivity C-reactive protein (hs CRP); homocysteine; requirements—measurable (ie, assay available, accurate, and cost-effective); adds information beyond that obtained from traditional risk factors; available treatment improves clinical outcomes

HDLHDL (“good cholesterol”): anti-inflammatory molecule, performs reverse

cholesterol transport (transports lipids from LDL to liver); functional HDL—inversely associated with CV risk; nonfunctional HDL—some patients have very high levels of HDL (>100 mg/dL) but have elevated CV risk; in trials, torcetrapib increased HDL levels by up to 150%, but mortality increased Tests: assays available, accurate, and cost-effective Added information: increasing HDL decreases mortality and CV events independently of LDL; decreasing HDL increases risk for death; raising HDL decreases risk, even among patients with optimized LDL levels Treatment: aerobic exercise (≈30 min/day) raises HDL levels up to 5% and lowers triglycerides; tobacco cessation raises HDL levels up to 10%; each kilogram of weight loss (for patients with BMI >25) increases HDL; moderate consistent use of alcohol (0-1 drinks/day for women; 1-2 drinks/day for men) raises HDL up to 12% (however, inconsistent or heavier drinking has multiple negative effects); medications—statins and thiazolidinediones (TZDs) modestly raise HDL; fibrates raise HDL 10% to 20%; niacin therapy results in most significant increases in HDL; most patients can tolerate 500 mg (especially when taken with food); new formulations may reduce adverse effects (eg, flushing, dyspepsia)

Raising HDL levels decreases cardiovascular (CV) risk among patients

with optimized LDL levels.A) TrueB) False

C) Unknown

Answer

A) True

Which of the following strategies raise HDL levels?

1. Anaerobic exercise 2. Aerobic exercise

3. Smoking cessation 4. Consistent modest consumption

of alcohol

A) 1,2B) 2,3

C) 2,3,4D) 1,3,4

Answer

C) 2,3,4

Apolipoprotein A-1

Apolipoprotein A-1: coats HDL molecules; critical for antioxidant and anti-inflammatory functions of HDL; promotes reverse cholesterol transport; test—available, accurate, and reproducible; added information—good measure of functional HDL; associated with superior prediction of CV risk, compared to LDL or non-HDL levels; effect on management—treatment available (same approaches as for increasing HDL); unknown whether raising apo A-1 will have effect on clinical outcome (clinical trial in progress); note—assay does not require fasting

Apolipoprotein B

Apolipoprotein B: coats all non-HDL lipoproteins; provides direct measure of concentration of all atherogenic particles (LDL, very low-density lipoprotein [VLDL] and intermediate- density lipoproteins [IDL]); test—available (may be performed without fasting), accurate, reproducible, and cost-effective; added information—more predictive of CV risk than LDL or non-LDL levels; useful for assessing VLDL and IDL levels in patients taking statins; effect on management—unknown; cutoff levels not established; significant variance among ethnic populations; no large outcome trials

Lipoprotein [Lp](a)Lipoprotein [Lp](a): coats phospholipids; resembles

fibrinogen, so interferes with normal fibrinolysis; promotes atherogenesis; test—available and accurate; 90th percentiles established (39.0 mg/dL in men; 39.5 mg/dL in women); added information—independently associated with CV risk; associated with unstable angina and unstable plaque (promotes growth of new lesions); effect on management—no outcome studies available; limited medical therapies (primarily niacin, but also large [2-3 g] doses of neomycin); statins have no effect; test most useful for patients with known disease, or strong family history but normal lipid levels, and those with high LDL resistant to medical therapy

A lipid panel from a man, 46 yr of age, with recent history of nonfatal myocardial infarction

shows LDL of 110 mg/dL, HDL of 100 mg/dL, and mildly elevated

triglycerides. Which of the following tests would add useful

information for directing management?

A) Apolipoprotein A-1 (apo A-1)B) Apo B

Answer

A) Apolipoprotein A-1 (apo A-1)

Which test provides a measure of the total

concentration of atherogenic particles in

the serum?A) Apo A-1B) Apo B

C) Lipoprotein(a)D) High-sensitivity C-

reactive protein (hs-CRP)

Answer

B) Apo B

A man, 48 yr of age, with positive family history of CV

disease, suffers a nonfatal MI. A lipid panel reveals no major

abnormalities, but his lipoprotein(a) level is 50 mg/dL.

Which agent would be most useful for addressing his risk

factors?A) StatinB) Fish oilC) Niacin

Answer

C) Niacin

Triglycerides

Triglycerides: elevations associated with increased CV risk (may not be independent of other factors); important to identify etiology of elevation (eg, hypothyroidism, medication use [eg, diuretics, estrogen agents, antiretroviral agents, atypical antipsychotics, resins]; alcohol abuse) Tests: available, but measurements vary significantly from one day to next Added information: clinical trials show limited benefit of lowering triglycerides once LDL levels controlled; levels >200 mg/dL associated with increased risk in women; levels >500 mg/dL increase risk for pancreatitis (>1000 mg/dL requires immediate intervention) Effect on management: study in women showed that nonfasting (but not fasting) levels associated with CV events, independently of other risk factors; 2- to 4-hr postprandial measurement most useful (indication of body’s ability to clear triglycerides after meal), but difficult to implement; approaches to lowering triglycerides—weight loss; aerobic exercise; reducing intake of simple sugars; supplementation with omega-3 fatty acids; medical therapy (niacin; fibrates; statins [modest effect])

High-sensitivity C-reactive protein

High-sensitivity C-reactive protein: test—does not require fasting; widely available and accurate; added information— predicts risk independently of traditional risk factors; most useful in patients at intermediate risk; effect on management—small outcome study showed benefit of lowering CRP at all levels of LDL; larger outcome trial (in progress) looking at CRP reduction as primary prevention strategy in 15 000 patients with optimal LDL levels and intermediate to high CRP levels (randomized to placebo or rosuvastatin); approaches to lowering CRP—statin therapy; smoking cessation; aerobic exercise; BP control; achieving and maintaining optimal BMI

Use of which of the following serum markers is most supported by clinical

outcome trials?A) Apo B

B) Fasting level of triglycerides

C) hs-CRPD) Homocysteine

Answer

C) hs-CRP

Clinical CaseCase 1: man, 49 yr of age, with recent history

of inferior wall MI and 2-vessel angioplasty; evidence of 20% to 40% stenosis in other vessels; previously told that his cholesterol “was fine”; patient reports “social” smoking and drinking; considered low in premenopausal women), and slightly elevated triglycerides (<150 mg/dL desirable in women); hs CRP—3.2 mg/L (>3 mg/L signals high risk; >10 mg/L may signal cancer or collagen vascular disease)

What should you recommend?

Answer

management—aerobic exercise; smoking cessation (difficult);

hs-CRP remained elevated, so low-dose statin added

Clinical CaseCase 2: woman, 45 yr of age; routine lipid panel

shows total cholesterol 203 mg/dL, HDL 48 mg/dL, triglycerides 155 mg/dL, and LDL 124 mg/dL; current smoker (1.5 packs/day); positive family history (mother had MI at 64 yr of age); normal weight and heart rate; risk—intermediate, because of positive family history, low HDL (<50 mg/dL considered low in premenopausal women), and slightly elevated triglycerides (<150 mg/dL desirable in women); hs CRP—3.2 mg/L (>3 mg/L signals high risk; >10 mg/L may signal cancer or collagen vascular disease)

What should you recommend?

Answer

management—aerobic exercise; smoking cessation (difficult);

hs-CRP remained elevated, so low-dose statin added

Homocysteine

Homocysteine: test—inaccurate; highly variable; added information—does not independently predict risk; effect on management—multiple outcome studies show that lowering homocysteine levels (through folic acid supplementation) does not reduce CV risk and may increase some events (eg, unstable angina)

Summary

Summary: HDL—important for risk assessment and management;

apo A-1, apo B, and Lp(a)—potentially useful markers, but clinical outcome studies limited;

triglycerides—postprandial measurements may provide important information; fasting measures have limited value;

hs-CRP—likely valuable as marker of risk, but data from larger outcome trials not yet available;

homocysteine— not useful

You see a 23-year-old gravida 1 para 0 for her prenatal checkup at 38 weeks gestation. She complains of severe

headaches and epigastric pain. She has had an uneventful pregnancy to date and had a normal prenatal examination 2

weeks ago. Her blood pressure is 140/100 mm Hg. A urinalysis shows 2+ protein; she has gained 5 lb in the last

week, and has 2+ pitting edema of her legs. The most appropriate management at this point would

be:  (check one)A. Strict bed rest at home and reexamination within 48 hours

B. Admitting the patient to the hospital for bed rest and frequent monitoring of blood pressure, weight, and

proteinuriaC. Admitting the patient to the hospital for bed rest and monitoring, and beginning hydralazine (Apresoline) to

maintain blood pressure below 140/90 mm HgD. Admitting the patient to the hospital, treating with

parenteral magnesium sulfate, and planning prompt delivery either vaginally or by cesarean section

Answer• D. Admitting the patient to the hospital, treating with

parenteral magnesium sulfate, and planning prompt delivery either vaginally or by cesarean section

• Explanation: This patient manifests a rapid onset of preeclampsia at term. The symptoms of epigastric pain and headache categorize her preeclampsia as severe. These symptoms indicate that the process is well advanced and that convulsions are imminent. Treatment should focus on rapid control of symptoms and delivery of the infant. Ref: Cunningham FG, Gant NF, Leveno KJ, et al: Williams Obstetrics, ed 21. McGraw-Hill, 2001, pp 569-571, 591-592.

A 67-year-old Hispanic male comes to your office with severe periumbilical abdominal pain, vomiting, and diarrhea which began

suddenly several hours ago. His temperature is 37.0 degrees C (98.6 degrees F), blood pressure 110/76 mm Hg, and respirations 28/min. His abdomen is slightly distended, soft, and diffusely tender; bowel sounds are normal. Other findings include clear lungs, a rapid and irregularly

irregular heartbeat, and a pale left forearm and hand with no palpable left brachial pulse. Right arm and lower extremity pulses are normal. Urine

and stool are both positive for blood on chemical testing. His hemoglobin level is 16.4 g/dL (N 13.0–18.0) and his WBC count is 25,300/mm3 (N

4300–10,800). The diagnostic imaging procedure most likely to produce a specific diagnosis of his abdominal pain is:

A. Intravenous pyelography (IVP) B. Sonography of the abdominal aorta 

C. A barium enema D. Celiac and mesenteric arteriography 

E. Contrast venography

Answer

• D. Celiac and mesenteric arteriography  • Explanation: The sudden onset of severe abdominal pain, vomiting, and

diarrhea in a patient with a cardiac source of emboli and evidence of a separate embolic event makes superior mesenteric artery embolization likely. In this case, evidence of a brachial artery embolus and a cardiac rhythm indicating atrial fibrillation suggest the diagnosis. Some patients may have a surprisingly normal abdominal examination in spite of severe pain. Microscopic hematuria and blood in the stool may both occur with embolization. Severe leukocytosis is present in more than two-thirds of patients with this problem. Diagnostic confirmation by angiography is recommended. Immediate embolectomy with removal of the propagated clot can then be accomplished and a decision made regarding whether or not the intestine should be resected. A second procedure may be scheduled to reevaluate intestinal viability. Ref: Braunwald E, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, ed 15. McGraw-Hill, 2001, p 1699. 2) Townsend CM Jr: Sabiston Textbook of Surgery, ed 16. WB Saunders Co, 2001, p 1399.

A 49-year-old white female comes to your office complaining of painful, cold finger tips which turn white when she is hanging out her laundry. While there is no approved treatment

for this condition at this time, which one of the following drugs has been shown to be

useful?A. Propranolol (Inderal) B. Nifedipine (Procardia) 

C. Ergotamine/caffeine (Cafergot) D. Methysergide (Sansert)

Answer• B. Nifedipine (Procardia) • Explanation: At present there is no approved treatment for Raynaud’s

disease. However, patients with this disorder reportedly experience subjective symptomatic improvement with calcium channel antagonists. Nifedipine is the calcium channel blocker of choice in patients with Raynaud’s disease. Beta-blockers can produce arterial insufficiency of the Raynaud type, so propranolol and atenolol would be contraindicated. Drugs such as ergotamine preparations and methysergide can produce cold sensitivity, and should therefore be avoided in patients with Raynaud’s disease. Ref: Goldman L, Bennett JC (eds): Cecil Textbook of Medicine, ed 21. WB Saunders Co, 2000, pp 364-365. 2) Braunwald E, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, ed 15. McGraw-Hill, 2001, pp 1438-1439.

You perform a health maintenance examination on a 2-year-old white male. He is

asymptomatic and is meeting all developmental milestones. The only

significant finding is a grade 3/6 diastolic murmur heard at the right upper sternal

border. Which one of the following would be most appropriate at this time?

A. No further evaluation B. Referral to a pediatric cardiologist 

C. Reevaluation in 6 months D. Maintenance doses of digoxin

Answer• B. Referral to a pediatric cardiologist  • Explanation: Children who have a murmur that is

diastolic or is greater than 2/6 should be referred for cardiovascular evaluation, perhaps after an echocardiogram is obtained. Other reasons for referral include cardiac symptoms, abnormal splitting of S2, a murmur that increases on standing, a holosystolic murmur, or ejection clicks. Digoxin is not indicated at this point in this asymptomatic patient. Ref: McConnell ME, Adkins SB III, Hannon DW: Heart murmurs in pediatric patients: When do you refer? Am Fam Physician 1999;60(2):558-565.

 For long-term therapy, the most effective control of heart rate in

atrial fibrillation, both at rest and with exercise, occurs with which

one of the following?A. Digitalis 

B. Beta-adrenergic blockers C. Calcium channel blockers D. Class 1A antiarrhythmics

Answer• B. Beta-adrenergic blockers  • Explanation: For long-term therapy, beta-adrenergic

antagonist drugs provide the most effective control of heart rate in atrial fibrillation, both at rest and during exercise. Although calcium channel blockers also lower heart rate both at rest and with exercise, they are not as effective as beta-blockers. Digitalis is primarily effective in controlling the heart rate at rest, and often does not adequately control heart rate with exercise. The Class 1 antiarrhythmics are most useful in maintaining sinus rhythm and, in fact, may paradoxically increase heart rate. Ref: Lampert R, Ezekowitz MD: Management of arrhythmias. Clin Geriatr Med 2000;16(3):593-618.

. A 75-year-old white female develops deep-vein thrombosis of the left leg 1 week after hip surgery. The patient is started on low–

molecular-weight heparin (Lovenox). Daily monitoring while the patient is on low–

molecular-weight heparin should include which one of the following?

A. Prothrombin time B. Partial thromboplastin time 

C. Fibrinogen levels D. No routine coagulation tests

Answer

• D. No routine coagulation tests • Explanation: Routine coagulation tests such as

prothrombin time and partial thromboplastin time are insensitive measurements of Lovenox activity. Anti–factor Xa can be measured in patients with renal failure to monitor anticoagulation effects. Ref: Hardman JG, Limbird LE, Gilman AG (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics, ed 10. McGraw-Hill, 2001, p 1524

Elevated levels of which one of the following are associated with

atherosclerosis?A. Vitamin B6 B. Vitamin B12 

C. Folate D. Homocysteine

Answer

• D. Homocysteine • Explanation: Multiple prospective and case-

control studies have shown that a moderately elevated plasma homocysteine concentration is an independent risk factor for atherothrombotic vascular disease. Ref: Welch GN, Loscalzo J: Homocysteine and atherothrombosis. N Engl J Med 1998;338(15):1042-1050.

A 60-year-old African-American male was recently diagnosed with an

abdominal aortic aneurysm. A lipid profile performed a few months ago

revealed an LDL level of 125 mg/dL. You would now advise him that his goal

LDL level is:A. <100 mg/dL B. <130 mg/dL C. <150 mg/dL D. <160 mg/dL

Answer• A. <100 mg/dL • Explanation: Most physicians realize that the goal LDL level

for patients with diabetes mellitus or coronary artery disease is <100 mg/dL. Many may not realize that this goal extends to people with CAD-equivalent diseases, including peripheral artery disease, symptomatic carotid artery disease, and abdominal aortic aneurysm. Ref: Henley E, Chang L, Hollander S: Treatment of hyperlipidemia. J Fam Pract 2002;51(4):370-376. 2) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106(25):3143-3421.

You approach the administrator of your small-town hospital about the possibility of starting a cardiac

rehabilitation program. Which one of the following is true concerning such programs?

A. Patients should have a baseline exercise stress test before starting cardiac rehabilitation 

B. A standard exercise prescription is appropriate for all cardiac patients 

C. Cardiac rehabilitation has no effect on coronary risk factors 

D. Cardiac rehabilitation has no effect on exercise capacity 

E. Coronary events are frequent in rehabilitation settings

Answer

• A. Patients should have a baseline exercise stress test before starting cardiac rehabilitation 

• Explanation: Cardiac rehabilitation programs are safe and effective. Rates of coronary events in rehabilitation settings are very low. Cardiac rehabilitation consistently improves exercise capacity and has favorable effects on coronary risk factors, even without nutritional counseling. A baseline exercise stress test prior to starting cardiac rehabilitation is necessary to screen for exertional ischemia or arrhythmias, and serves as a basis for prescribing an exercise regimen. The exercise prescription is individualized based on results of the exercise stress test, the age of the patient, and the patient’s clinical status. Ref: Ades PA: Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med 2001;345(12):892-902.

Which one of the following is a risk factor for perioperative

arrhythmias?A. Supraventricular tachycardia 

B. Congestive heart failure C. Age >60 

D. Premature atrial contractions E. Past history of hyperthyroidism

Answer

• B. Congestive heart failure • Explanation: Significant predictors of intraoperative

and perioperative ventricular arrhythmias include preoperative ventricular (not supraventricular) ectopy, a history of congestive heart failure, and a history of cigarette smoking. Age and a history of hyperthyroidism are not significant predictors of perioperative ventricular arrhythmias. Ref: Sloan SB, Weitz HH: Postoperative arrhythmias and conduction disorders. Med Clin North Am 2001;85(5):1171-1189.

A 60-year-old white female presents with pain in her left calf on walking. The pain does not go away with continued walking, and is relieved by rest. She smokes one pack of cigarettes daily and has type 2 diabetes

mellitus which is only moderately controlled with oral agents. She has been fairly noncompliant with dietary measures, and has not been

interested in following your recommendations regarding medication for her hyperlipidemia. She is unable to do many of the things that she

previously enjoyed doing, such as playing golf. Her ankle-brachial index at rest on the left is 0.60 and on the right is 1.10. Which one of the following is true regarding management of this patient’s peripheral

vascular disease?A. In order to improve functional capacity, exercise training should be

encouraged B. Her goal LDL-cholesterol level is <130 mg/dL 

C. Improved control of her diabetes with insulin will slow the progression of her disease 

D. If she requires femoropopliteal bypass surgery, estrogen should be given postoperatively for secondary prevention

Answer• A. In order to improve functional capacity, exercise training

should be encouraged  • Explanation: Exercise therapy for peripheral vascular disease

(PVD) improves maximal treadmill walking distance and functional capacity. A rigorous exercise-training program may be as beneficial as bypass surgery and more beneficial than angioplasty. The goal LDL-cholesterol level in patients with established atherosclerotic vascular disease, including those with PVD (and all patients with diabetes mellitus) should be <100 mg/dL. Tight control of diabetes mellitus has not been shown to favorably affect PVD. Ref: Hiatt WR: Medical treatment of peripheral arterial disease and claudication. N Engl J Med 2001;344(21):1608-1621

Which one of the following would be most likely to have secondary hypertension?

A. A 39-year-old white male who weighs 119 kg (262 lb) and whose blood pressure is 142/94 mm Hg B. A 48-year-old African-American female with left ventricular hypertrophy on echocardiography whose

blood pressure is 162/98 mm Hg C. A 62-year-old African-American male with a

strong family history of hypertension D. A 78-year-old white female with abdominal bruits

whose blood pressure is 182/102 mm Hg E. An 88-year-old white male with hemiparesis due to a previous stroke whose blood pressure is 192/88

mm Hg

Answer• D. A 78-year-old white female with abdominal bruits whose blood

pressure is 182/102 mm Hg  • Explanation: Physical findings which suggest secondary hypertension

include the presence of abdominal bruits, particularly those that lateralize or have a diastolic component. Excess body weight is correlated closely with increased blood pressure, but is not a cause of secondary hypertension. Hypertension is the most important risk factor for stroke, but a history of stroke is not an indication of secondary hypertension. Left ventricular hypertrophy is a result of hypertension, but is not an indication of secondary hypertension. The prevalence of hypertension is greater in African-Americans than in whites, but African-American race is not a risk factor for secondary hypertension. Ref: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157(21):2413-2440.

A 35-year-old African-American female has just returned home from a vacation in Hawaii. She presents to your office

with a swollen left lower extremity. She has no previous history of similar problems. Homan’s sign is positive, and ultrasonography reveals a noncompressible vein in the left

popliteal fossa extending distally. Which one of the following is true in this situation?

A. Monotherapy with an initial 10-mg loading dose of warfarin (Coumadin) would be appropriate 

B. Enoxaparin (Lovenox) should be administered at a dosage of 1 mg/kg subcutaneously twice a day 

C. The incidence of thrombocytopenia is the same with low–molecular-weight heparin as with unfractionated heparin 

D. The dosage of warfarin should be adjusted to maintain the INR at 2.5–3.5 

E. Anticoagulant therapy should be started as soon as possible and maintained for 1 year to prevent deep vein

thrombosis (DVT) recurrence

Answer

• B. Enoxaparin (Lovenox) should be administered at a dosage of 1 mg/kg subcutaneously twice a day 

• Explanation: The use of low-molecular-weight heparin allows patients with acute deep vein thrombosis (DVT) to be managed as outpatients. The dosage is 1 mg/kg subcutaneously twice daily. Patients chosen for outpatient care should have good cardiopulmonary reserve, normal renal function, and no risk for excessive bleeding. Oral anticoagulation with warfarin can be initiated on the first day of treatment after heparin loading is completed. Monotherapy with warfarin is inappropriate. The incidence of thrombocytopenia with low–molecular-weight heparin is lower than with conventional heparin. The INR should be maintained at 2.0–3.0 in this patient. The 2.5–3.5 range is used for patients with mechanical heart valves. The therapeutic INR should be maintained for 3–6 months in a patient with a first DVT related to travel. Ref: Weismantel D: Treatment of the patient with deep vein thrombosis. J Fam Pract 2001;50(3):249-256. 2) Kasper DL, Braunwald E, Fauci AS, et al (eds): Harrison’s Principles of Internal Medicine, ed 16. McGraw-Hill, 2005, pp 570, 1491-1429.

Which one of the following historical features is most

suggestive of congestive heart failure in a 6-month-old white

male presenting with tachypnea?A. Diaphoresis with feeding 

B. Fever C. Nasal congestion 

D. Noisy respiration or wheezing E. Staccato cough

Answer• A. Diaphoresis with feeding  • Explanation: Symptoms of congestive heart failure in infants are often

related to feedings. Only small feedings may be tolerated, and dyspnea may develop with feedings. Profuse perspiration with feedings, is characteristic, and related to adrenergic drive. Older children may have symptoms more similar to adults, but the infant’s greatest exertion is related to feeding. Fever and nasal congestion are more suggestive of infectious problems. Noisy respiration or wheezing does not distinguish between congestive heart failure, asthma, and infectious processes. A staccato cough is more suggestive of an infectious process, including pertussis. Ref: Strange GR, Ahrens WR, Lelyveld S, et al (eds): Pediatric Emergency Medicine: A Comprehensive Study Guide, ed 2. American College of Emergency Physicians, 2002, pp 216, 226, 246. 2) Behrman RE, Kliegman RM, Jenson HB (eds): Nelson Textbook of Pediatrics, ed 17. Saunders, 2004, p 1583.

In which one of the following clinical situations would it be most appropriate to use a beta-blocker

that has intrinsic sympathomimetic activity, such as acebutolol (Sectral) or pindolol (Visken)?

A. As a cardioprotective agent post myocardial infarction 

B. In a hypertensive patient with symptomatic bradycardia while taking metoprolol (Lopressor) 

C. In a hypertensive patient with diabetes mellitus D. In a hypertensive patient with asthma 

E. To maintain sinus rhythm in a patient with chronic atrial fibrillation

Answer• B. In a hypertensive patient with symptomatic bradycardia while

taking metoprolol (Lopressor)  • Explanation: Beta-blockers with intrinsic sympathomimetic activity

(ISA) are less beneficial in reducing mortality post myocardial infarction, and for this reason are not recommended for ischemic heart disease. They have a potential advantage in only one clinical situation. Since they tend to lower heart rates less, they may be beneficial in patients with symptomatic bradycardia while taking other beta-blockers. All beta-blockers should be used cautiously in patients with diabetes or asthma. Only sotalol, which delays ventricular depolarization, has been shown to be effective for maintenance of sinus rhythm in patients with chronic atrial fibrillation. Ref: Which beta-blocker? Med Lett Drugs Ther 2001;43:9-12.

You are treating a 50-year-old white male for diabetes mellitus and hyperlipidemia. At the time of his initial presentation 1 year ago, his hemoglobin A1c was 8.0% (N 3.8–6.4), LDL 130 mg/dL, HDL 28

mg/dL, and triglycerides 450 mg/dL. After treatment with metformin (Glucophage) and high-dose simvastatin (Zocor), his most recent

laboratory evaluation revealed a hemoglobin A1c of 6.2%, LDL 95 mg/dL, HDL 32 mg/dL, and triglycerides 300 mg/dL. The patient has not had any documented coronary or peripheral vascular disease. His family

history is positive for a myocardial infarction in his father at age 55. He is a nonsmoker. He has a body mass index (BMI) of 28 and has been unable

to lose weight. His blood pressure is well controlled on enalapril (Vasotec). What is the most appropriate management of his elevated

triglycerides?A. No specific treatment 

B. Switch from metformin to a sulfonylurea such as glyburide (Micronase, DiaBeta) or glipizide (Glucotrol) 

C. Addition of a fibrate such as gemfibrozil (Lopid) or fenofibrate (Tricor) 

D. Addition of cholestyramine (Questran)

Answer

• C. Addition of a fibrate such as gemfibrozil (Lopid) or fenofibrate (Tricor)  • Explanation: Although the significance of elevated triglycerides and a low

HDL in low-risk patients is somewhat uncertain, in a high-risk patient such as a diabetic, improvement in these results will lower the risk of subsequent cardiac events. In diabetics, metformin and thiazolidinediones (e.g., rosiglitazone) are more likely to improve lipid levels than are sulfonylureas. Nicotinic acid is problematic in diabetics, as it tends to cause deterioration in glucose control. Fibrates are good choices for this patient because they will lower the triglyceride level and raise the HDL level. Exercise and weight loss are likely to be helpful as well. Cholestyramine will raise triglyceride levels. Ref: Donahoo WT, Eckel RH: Evaluation, treatment, and implications of hypertriglyceridemia. Primary Care Case Reviews 2001;4(2):53-61. 2) Position Statement: Management of dyslipidemia in adults with daibetes. Diabetes Care 2002;25(suppl):574-577.

Which one of the following procedures carries the highest

risk for postoperative deep venous thrombosis?

A. Abdominal hysterectomy B. Coronary artery bypass graft C. Transurethral prostatectomy 

D. Lumbar laminectomy E. Total knee replacement

Answer• E. Total knee replacement • Explanation: Neurosurgical procedures, particularly those with penetration of

the brain or meninges, and orthopedic surgeries, especially those of the hip, have been linked with the highest incidence of venous thromboembolic events. The risk is due to immobilization, venous injury and stasis, and impairment of natural anticoagulants. For total knee replacement, hip fracture surgery, and total hip replacement, the prevalence of DVT is 40%-80%, and the prevalence of pulmonary embolism is 2%-30%. Other orthopedic procedures, such as elective spine procedures, have a much lower rate, approximately 5%. The prevalence of DVT after a coronary artery bypass graft is approximately 5%, after transurethral prostatectomy <5%, and after abdominal hysterectomy approximately 16%. Ref: Geerts WH, Heit JA, Clagett GP, et al: Prevention of venous thromboembolism. Chest 2001;119(1 Suppl):132S-175S. 2) Kaboli P, Henderson MC, White RH: DVT prophylaxis and anticoagulation in the surgical patient. Med Clin North Am 2003;87(1):77-110.

Which one of the following treatments has been shown to produce the most benefit for

patients with peripheral vascular disease?

A. Smoking cessation B. Diet modification 

C. Aspirin D. Pentoxifylline (Trental) 

E. Lipid-lowering drugs

Answer

• A. Smoking cessation • Explanation: Patients with peripheral vascular

disease who stop smoking have a twofold increase in their 5-year survival rate. Diet modification and lipid-lowering drugs can slow progression, but not as dramatically. Aspirin and pentoxifylline are minimally effective. Ref: Schainfeld RM: Management of peripheral arterial disease and intermittent claudication. J Am Board Fam Pract 2001;14(6):443-450.

A 13-year-old male is found to have hypertrophic cardiomyopathy. His father also had hypertrophic cardiomyopathy, and died

suddenly at age 38 following a game of tennis. The boy’s mother asks you for advice regarding his condition. What advice should

you give her?A. He may participate in noncontact sports B. He should receive lifelong treatment with

beta-blockers C. His condition usually decreases lifespan D. His hypertrophy will regress with age 

E. His siblings should undergo echocardiography

Answer

• E. His siblings should undergo echocardiography • Explanation: Hypertrophic cardiomyopathy is an

autosomal dominant condition and close relatives of affected individuals should be screened. The hypertrophy usually stays the same or worsens with age. This patient should not participate in strenuous sports, even those considered noncontact. Beta-blockers have not been shown to alter the progress of the disease. The mortality rate is believed to be about 1%, with some series estimating 5%. Thus, in most cases lifespan is normal. Ref: Maron BJ: Hypertrophic cardiomyopathy. JAMA 2002;287(10):1308-1320.

 A 70-year-old white male has a slowly enlarging, asymptomatic abdominal aortic aneurysm. You

should usually recommend surgical intervention when the

diameter of the aneurysm approaches:

Answer• C. 5.5 cm  • Explanation: Based on recent clinical trials, the most common recommendation

for surgical repair is when the aneurysm approaches 5.5 cm in diameter. Two large studies, the Aneurysm Detection and Management (ADAM) Veteran Affairs Cooperative Study, and the United Kingdom Small Aneurysm Trial, failed to show any benefit from early surgery for men with aneurysms less than 5.5 cm in diameter. The risks of aneurysm rupture were 1% or less in both studies, with 6-year cumulative survivals of 74% and 64%, respectively. Interestingly, the risk for aneurysm rupture was four times greater in women, indicating that 5.5 cm may be too high, but a new evidence-based threshold has not yet been defined. Ref: Lederle FA, Wilson SE, Johnson GR, et al: Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346(19):1437-1444. 2) United Kingdom Small Aneurysm Trial Participants: Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346(19):1445-1452. 3) Powell JT, Greenhalgh RM: Small abdominal aortic aneurysms. N Engl J Med 2003;348(19):1895-1901

A 75-year-old otherwise healthy white female states that she has passed out three times in the last month while walking briskly during her daily walk with the local senior citizens

mall walkers’ club. This history would suggest which one of the following as the

etiology of her syncope?A. Vasovagal syncope 

B. Transient ischemic attack C. Orthostatic hypotension 

D. Atrial myxoma E. Aortic stenosis

Answer• E. Aortic stenosis • Explanation: Syncope with exercise is a manifestation of organic heart

disease in which cardiac output is fixed and does not rise (or even fall) with exertion. Syncope, commonly on exertion, is reported in up to 42% of patients with severe aortic stenosis. Vasovagal syncope is associated with unpleasant stimuli or physiologic conditions, including sights, sounds, smells, sudden pain, sustained upright posture, heat, hunger, and acute blood loss. Transient ischemic attacks are not related to exertion. Orthostatic hypotension is associated with changing from a sitting or lying position to an upright position. Atrial myxoma is associated with syncope related to changes in position, such as bending, changing from sitting to lying, or turning over in bed. Ref: Kapoor WN: Syncope in older persons. J Am Geriatr Soc 1994;42(4):426-436. 2) Hazzard WR, Blass JP, Ettinger WH Jr, et al (eds): Principles of Geriatric Medicine and Gerontology, ed 4. McGraw-Hill, 1999, pp 1522-1534.

Which one of the following drug classes is preferred for treating

hypertension in patients who also have diabetes mellitus?

A. Centrally-acting sympatholytics 

B. Alpha-blocking agents C. Beta-blocking agents 

D. ACE inhibitors E. Calcium channel blockers

Answer

• D. ACE inhibitors  • Explanation: ACE inhibitors have proven beneficial in

patients who have either early or established diabetic renal disease. They are the preferred therapy in patients with diabetes and hypertension, according to guidelines from the American Diabetes Association, the National Kidney Foundation, the World Health Organization, and the JNC VII report. Ref: Konzem SL, Devore VS, Bauer DW: Controlling hypertension in patients with diabetes. Am Fam Physician 2002;66(7):1209-1214. 2) Chobanian AV, Bakris GL, Black HR, et al: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-1252.

A 75-year-old Hispanic male presents with dyspnea on exertion which has worsened over the last several months. He denies chest pain and syncope, and was fairly active until the

shortness of breath slowed him down recently. You hear a grade 3/6 systolic ejection murmur at the right upper sternal

border which radiates into the neck. Echocardiography reveals aortic stenosis, with a mean transvalvular gradient of

55 mm Hg and a calculated valve area of 0.6 cm2. Left ventricular function is normal. Which one of the following is

appropriate management for this patient?A. Aortic valve replacement B. Aortic balloon valvotomy 

C. Medical management with beta-blockers and nitrates D. Watchful waiting until the gradient is severe enough for

treatment E. Deferring the decision pending results of an exercise stress

test

Answer

• A. Aortic valve replacement 

• Explanation: Since this patient’s mean aortic-valve gradient exceeds 50 mm Hg and the aortic-valve area is not larger than 1 cm2, it is likely that his symptoms are due to aortic stenosis. As patients with symptomatic aortic stenosis have a dismal prognosis without treatment, prompt correction of his mechanical obstruction with aortic valve replacement is indicated. Medical management is not effective, and balloon valvotomy only temporarily relieves the symptoms and does not prolong survival. Patients who present with dyspnea have only a 50% chance of being alive in 2 years unless the valve is promptly replaced. Exercise testing is unwarranted and dangerous in patients with symptomatic aortic stenosis. Ref: Carabello BA: Aortic stenosis. N Engl J Med 2002;346(9):677-682.

A 73-year-old white male nursing-home resident has Alzheimer’s dementia and hypertension. He has been

weaker and less responsive over the last week and has gained 8 lb. On physical examination he has

normal vital signs with a heart rate of 110 beats/min, but is noted to have marked lower extremity edema and presacral edema. Laboratory evaluation shows a

serum sodium level of 122 mmol/L (N 135–145). Which one of the following is the most likely cause

of his hyponatremia?A. Diuretic use 

B. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 

C. Addison’s disease D. Congestive heart failure E. Psychogenic polydipsia

Answer• D. Congestive heart failure  • Explanation: Most decision trees for the evaluation of hyponatremia

begin with an assessment of volume status; edema reflects volume overload and increased total body sodium caused by congestive heart failure, cirrhosis, or renal failure. If edema is absent, plasma osmolality should be determined. SIADH, Addison’s disease (hypoadrenalism), diuretic use, and renal artery stenosis all lower serum osmolality. Urine electrolytes help distinguish the other conditions: psychogenic polydipsia causes low urine sodium, while SIADH and hypoadrenalism cause inappropriately elevated urine sodium. Diuretic use, a very common cause of hyponatremia in the geriatric population, causes hypovolemic hyponatremia and can be associated with either high or low urine sodium, but there is often concomitant hypokalemia. Ref: Goh KP: Management of hyponatremia. Am Fam Physician 2004;69(10):2387-2394.

 A 28-year-old gravida 2 para 1 presents to the emergency department at 16 weeks' gestation. She has noted the sudden onset of dyspnea, pleuritic chest pain, and mild hemoptysis. Both calves are mildly edematous and somewhat tender. A lung scan shows a high probability of pulmonary emboli.

Which one of the following would be appropriate management at this time?

A. Placement of an inferior venous umbrella filter B. Intravenous heparin for 5–10 days followed by

subcutaneous heparin for the duration of the pregnancy C. Intravenous heparin for 5–10 days followed by warfarin

anticoagulation D. Warfarin therapy only, with the prothrombin time

maintained at 18–20 seconds (INR 2.0–3.0) E. Aspirin, 81 mg/day throughout the pregnancy

Answer• B. Intravenous heparin for 5–10 days followed by subcutaneous heparin for the duration of

the pregnancy  • Explanation: The risk of pulmonary embolism is five times higher in pregnant women than

in nonpregnant women of similar age, and venous thromboembolism is a leading cause of illness and death during pregnancy. Warfarin, which readily crosses the placenta, should be avoided throughout pregnancy. It is definitely teratogenic during the first trimester, and extensive fetal abnormalities have been associated with exposure to warfarin in any trimester. Because heparin does not cross the placenta, it is considered the safest anticoagulant to use during pregnancy. Initially, patients with venous thromboembolism during pregnancy should be managed with heparin given according to the recommendations for nonpregnant patients. These women should receive intravenous heparin for 5–10 days followed by subcutaneous heparin for the duration of the pregnancy. Warfarin can be given after delivery, since it is not present in breast milk. The indications for placement of an inferior vena cava filter are not changed by pregnancy, and include any contraindication to anticoagulant therapy, the occurrence of heparin-induced thrombocytopenia, and recurrence of pulmonary embolism in a patient receiving adequate anticoagulant therapy. There are no data to support the use of aspirin for treatment or prophylaxis of pulmonary embolism either during or after pregnancy. Ref: Toglia MR, Weg JG: Venous thromboembolism during pregnancy. N Engl J Med 1996;335(2):108-114.

Which one of the following is considered a contraindication to the use of beta-blockers

for congestive heart failure?A. Mild asthma 

B. Symptomatic heart block C. New York Heart Association (NYHA)

Class III heart failure D. NYHA Class I heart failure in a patient

with a history of a previous myocardial infarction 

E. An ejection fraction <30%

Answer

• B. Symptomatic heart block  • Explanation: According to several randomized, controlled trials,

mortality rates are improved in patients with heart failure who receive beta-blockers in addition to diuretics, ACE inhibitors, and occasionally, digoxin. Contraindications to beta-blocker use include hemodynamic instability, heart block, bradycardia, and severe asthma. Beta-blockers may be tried in patients with mild asthma or COPD as long as they are monitored for potential exacerbations. Beta-blocker use has been shown to be effective in patients with NYHA Class II or III heart failure. There is no absolute threshold ejection fraction. Beta-blockers have also been shown to decrease mortality in patients with a previous history of myocardial infarction, regardless of their NYHA classification. Ref: Chavey WE II: The importance of beta blockers in the treatment of heart failure. Am Fam Physician 2000;62(11):2453-2462.

Which one of the following is the leading cause of death in

women?A. Breast cancer B. Lung cancer 

C. Ovarian cancer D. Osteoporosis 

E. Cardiovascular disease

Answer

• E. Cardiovascular disease • Explanation: Cardiovascular disease is the leading cause of death among

women. According to the CDC, 29.3% of deaths in females in the U.S. in 2001 were due to cardiovascular disease and 21.6% were due to cancer, with most resulting from lung cancer. Breast cancer is the third most common cause of cancer death in women, and ovarian cancer is the fifth most common. Ref: Anderson RN, Smith BL: Deaths: Leading causes for 2001. NatlVital Stat Rep 2003 Nov 7;52(9). Available at www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_09.pdf. 2) Centers for Disease Control: CDC Office of Women’s Health. Leading causes of death females—United States, 2001. Available at www.cdc.gov/od/spotlight/nwhw/lcod.htm. 3) American Cancer Society: Cancer Facts and Figures 2002. Publication number 02-250M-No. 5008.02. 4) Centers for Disease Control and Prevention: CDC recommendations regarding selected conditions affecting women’s health. MMWR 2000;49(RR-2):1-73.

Which one of the following should be considered in geriatric patients when a long airline flight

is planned?A. Hypoxia with desaturation 

B. Temporal disorientation C. Barotitis 

D. Dehydration E. Deep venous thrombophlebitis

Answer• E. Deep venous thrombophlebitis • Explanation: ”Coach class thrombosis,” deep venous thrombosis or

pulmonary embolism associated with cramped conditions on long airline flights, is in fact a real phenomenon. However, the risk is small and only those already at increased risk of venous thromboembolism need to be concerned about it. The known complications of venous stasis must be avoided by the prophylactic use of ambulation and exercises during long flights. Patients at increased risk or presently on antithrombotic medications must be carefully monitored prior to their trip. Ref: Brotman DJ, Jaffer A: ‘Coach class thrombosis’: Is the risk real? What do we tell our patients? Cleve Clin J Med 2002;69(11):832-833, 837. 2) Tierney LM Jr (ed): Current Medical Diagnosis & Treatment 2002. McGraw-Hill, 2002, pp 1606-1607.

A 72-year-old African-American male comes to your office for surgical clearance to undergo elective hemicolectomy for recurrent diverticulitis. The patient suffered an uncomplicated

acute anterior-wall myocardial infarction approximately 18 months ago. A stress test was normal 2 months after he was

discharged from the hospital. Currently, the patient feels well, walks while playing nine holes of golf three times per week, and is able to walk up a flight of stairs without chest pain or

significant dyspnea. Findings are normal on a physical examination. Which one of the following would be most

appropriate for this patient prior to surgery?A. A 12-lead resting EKG 

B. A graded exercise stress test C. A stress echocardiogram 

D. A persantine stressed nuclear tracer study (technetium or thallium) 

E. Coronary angiography

Answer• A. A 12-lead resting EKG • Explanation: The current recommendations from the American College of

Cardiology and the American Heart Association on preoperative clearance for noncardiac surgery state that preoperative intervention is rarely needed to lower surgical risk. Patients who are not currently experiencing unstable coronary syndrome, severe valvular disease, uncompensated congestive heart failure, or a significant arrhythmia are not considered at high risk, and should be evaluated for most surgery primarily on the basis of their functional status. If these patients are capable of moderate activity (greater than 4 METs) without cardiac symptoms, they can be cleared with no stress testing or coronary angiography for an elective minor or intermediate-risk operation such as the one this patient is to undergo. A resting 12-lead EKG is recommended for males over 45, females over 55, and patients with diabetes, symptoms of chest pain, or a previous history of cardiac disease. Ref: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery--Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2002;105(10):1257-1267.

. Patients with Wolff-Parkinson-White syndrome who have episodic

symptomatic supraventricular tachycardia or atrial fibrillation

benefit most from:A. Episodic intravenous digoxin 

B. Long-term oral digitalis C. Episodic beta-blockers 

D. Radiofrequency catheter ablation of bypass tracts

Answer• D. Radiofrequency catheter ablation of bypass tracts • Explanation: Radiofrequency catheter ablation of bypass

tracts is possible in over 90% of patients and is safer and more cost effective than surgery, with a similar success rate. Intravenous and oral digoxin can shorten the refractory period of the accessory pathway, and increase the ventricular rate, causing ventricular fibrillation. Beta-blockers will not control the ventricular response during atrial fibrillation when conduction proceeds over the bypass tract. Ref: Kasper DL, Braunwald E, Fauci AS, et al (eds): Harrison’s Principles of Internal Medicine, ed 16. McGraw-Hill, 2005, pp 1347-1351.