Transcript Preventing Atherosclerotic Vascular Disease

Preventing Atherosclerotic
Vascular Disease
Recommendations for
Antiviral Treatment of H1N1
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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
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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 atrisk 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
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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
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Rapid consumption of tobacco, intended
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to make the last experience with
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tobacco unpleasant to decrease the
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likelihood of relapse.
• Brand switching
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Consumption of a different brand of tobacco
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that is stronger to make the last experience
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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
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
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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?
Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin
Simvastatin
A) 1,6
B) 1,3,6
C) 4,5
D) 2,4,5
Answer
1. Atorvastatin
2. Lovastatin
3. Simvastatin
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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-highdensity 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 statin
Bile acid resin plus niacin
Statin plus fibrate
Statin plus antioxidants
A) 1
B) 1,2
C) 1,3
D) 1,4
Answer
1. Bile acid resin plus statin
2. Bile acid resin plus niacin
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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,
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
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 LDLC and hsCRP (compared to simvastatin alone)
• but no additional improvement in carotid intimamedial thickness
• finding led to concernabout extrapolating effects on
markers of risk (eg, hsCRP) to CV outcomes (new
Statins
• Safety and tolerability: although generally safe and welltolerated,
• 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
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
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
Non–HDL-C
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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
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
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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)
Questions and answers
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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 HDLC have residual risk for atherosclerosis; important to
address all aspects of dyslipidemia
• triglycerides—independent predictor of CV disease
• Framingham study found triglyceride level and HDLC 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
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• 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 lowdensity lipoproteins [VLDL], intermediatedensity 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
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Fibrates
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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
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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.
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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
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"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
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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 riskand 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) 1,2,3,4
B) 1,3,5
C) 2,3,4
D) 2,3,5
Answer
A. 1, 2, 3, 4
Medical therapy
Medical 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;
Statins
Statins: 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
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) Fenofibrate
B) Gemfibrozil
C) Ezetimibe
D) Niacin
Answer
B) Gemfibrozil
Lowering LDL targets
Lowering 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
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
patients
D) 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/dL
B) <80 mg/dL
C) <70 mg/dL
D) 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
HDL
HDL (“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
Raising HDL levels
decreases cardiovascular
(CV) risk among patients
with optimized LDL levels.
A) True
B) 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) 1,2
B) 2,3
C) 2,3,4
D) 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
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 costeffective; 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
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,
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-1
B) Apo B
C) Lipoprotein(a)
D) High-sensitivity Creactive 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) Statin
B) Fish oil
C) 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;
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
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-CRP
D) Homocysteine
Answer
C) hs-CRP
Clinical Case
Case 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 Case
Case 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
proteinuria
C. Admitting the patient to the hospital for bed rest and
monitoring, and beginning hydralazine (Apresoline) to
maintain blood pressure below 140/90 mm Hg
D. Admitting the patient to the hospital, treating with
parenteral magnesium sulfate, and planning prompt delivery
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. McGrawHill, 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, betaadrenergic 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 betablockers. 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 deepvein 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 casecontrol 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):11711189.
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 AfricanAmerican 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 betablockers 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):24532462.
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 02250M-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-ParkinsonWhite 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.