Jurnal Stroke 2017 PDF

Review Article
Stroke Epidemiology
Address correspondence to
Dr Cheryl Bushnell,
Department of Neurology,
Wake Forest Baptist Health,
and Risk Factor Medical Center Boulevard,

Winston Salem, NC 27157,
cbushnel@wakehealth.edu.
Management Relationship Disclosure:

Dr Guzik reports no
disclosure. Dr Bushnell
receives research/grant
Amy Guzik, MD; Cheryl Bushnell, MD, MHS support from the
Patient-Centered Outcomes
Research Institute
(PCS-1403-14532).
ABSTRACT
Unlabeled Use of
Purpose of Review: Death from stroke has decreased over the past decade, with Products/Investigational
stroke now the fifth leading cause of death in the United States. In addition, the Use Disclosure:
Drs Guzik and Bushnell report
incidence of new and recurrent stroke is declining, likely because of the increased no disclosures.
use of specific prevention medications, such as statins and antihypertensives. Despite * 2017 American Academy
these positive trends in incidence and mortality, many strokes remain preventable. The of Neurology.
major modifiable risk factors are hypertension, diabetes mellitus, tobacco smoking,
and hyperlipidemia, as well as lifestyle factors, such as obesity, poor diet/nutrition, and
physical inactivity. This article reviews the current recommendations for the manage-
ment of each of these modifiable risk factors.
Recent Findings: It has been documented that some blood pressure medications
may increase variability of blood pressure and ultimately increase the risk for stroke.
Stroke prevention typically includes antiplatelet therapy (unless an indication for anti-
coagulation exists), so the most recent evidence supporting use of these drugs is
reviewed. In addition, emerging risk factors, such as obstructive sleep apnea, electronic
cigarettes, and elevated lipoprotein (a), are discussed.
Summary: Overall, secondary stroke prevention includes a multifactorial approach.
This article incorporates evidence from guidelines and published studies and uses an
illustrative case study throughout the article to provide examples of secondary prevention
management of stroke risk factors.
Continuum (Minneap Minn) 2017;23(1):15–39.
INTRODUCTION overall prevalence of 2.6% in those

This article describes the incidence, over 20 years of age between 2009 and
prevalence, and mortality associated 2012.2 Approximately 85% of strokes
with ischemic stroke. In addition, the are ischemic, the main focus of this ar-
unresolved health disparities related ticle.2 In addition, 17.8% of those over
to ischemic stroke are described. The 45 years of age have experienced
best evidence for management of each stroke symptoms,3 and silent cerebral
modifiable risk factor is also described, infarction is seen in approximately 6%
with the exception of atrial fibrillation. to 28% of the population, increasing
For more information on atrial fibrilla- with age (Figure1-1).2 The risk of
tion, refer to the article “Cardioembolic recurrent stroke is approximately
Stroke” by Cumara B. O’Carroll, MD, 20% at 5 years.4,5
MPH, and Kevin M. Barrett, MD, MSc,1 Over the past 30 years or more, both
in this issue of Continuum. stroke incidence and mortality have
decreased. The rate of stroke in patients
EPIDEMIOLOGY OF STROKE on Medicare over 65 years of age de-
Stroke is the fifth leading cause of clined 40% from 1988 to 2008,6 and the
death in the United States, with an age-adjusted stroke death rate decreased
Continuum (Minneap Minn) 2017;23(1):15–39 ContinuumJournal.com 15
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Epidemiology and Risk Factors
KEY POINT
h Stroke incidence and
mortality have declined
in recent decades,
correlating with
improved risk factor
management.
FIGURE 1-1 Prevalence of stroke by age and sex.

Reprinted with permission from Mozaffarian D, et al, Circulation.2
B 2015 American Heart Association, Inc.
33.7% from 2003 to 2013.2 The rate of versus 58.9% decline).2 Differences in
recurrent stroke is declining as well. stroke risk are seen with race and eth-
In control patients pooled from stroke nicity as well. Overall, the stroke in-
prevention trials, the annual rate of cidence was higher in blacks than in
recurrent stroke fell from 8.71% in the whites in the REasons for Geographic
1960s to 4.98% in the 2000s,7 with the And Racial Differences in Stroke
current annual rate estimated to be (REGARDS) cohort, although this dis-
between 3% and 4%.8 Recurrent stroke parity was more prominent in the
is associated with a larger risk factor young, with a black to white incidence
burden,9 and improvements in stroke rate ratio of 4.02 in those 45 to 54 years
prevention over recent decades corre- of age and 0.86 in those over 85 years
spond to improved risk factor manage- of age.13 While a decline in incidence
ment, including higher rates of statin was seen in whites between 1990 and
(4% to 41.4%) and antihypertensive 2005, stroke incidence remained the
(53% to 73.5%) use between 1992 same in blacks.14 The mean age of
and 2008.6 stroke death is younger in blacks than
Unfortunately, disparities in stroke whites,2 and while death rates declined
risk exist, and the decline has not been by about 50% in all racial groups, rates
universal across all subgroups of the remain higher in blacks (65.7% versus
population. While stroke is more com- 46.9% in whites and 39.6% in Asians).2
mon in men than women when young Mexican Americans are also seen to have
and middle-aged,10 women have a a higher stroke incidence in younger
higher lifetime risk of stroke than men age groups and younger age at stroke
(20% to 21% versus 14% to 17%) with death than non-Hispanic whites.2,15
poorer functional outcomes.11,12 A In the United States, perhaps the
greater decline in age-adjusted death most dramatic are the geographic dis-
rate was seen in men than women be- parities. Mortality is 20% higher in the
tween 1981 and 2013 (61.4% decline stroke belt, identified as North Carolina,
16 ContinuumJournal.com February 2017

KEY POINTS
South Carolina, Georgia, Tennessee, solute number of stroke deaths in- h Disparities in stroke
Mississippi, Alabama, Louisiana, and creased over that time.2,19,20 incidence and mortality
Arkansas. Within the “buckle” of the still exist, particularly
stroke belt, mortality is even higher at RISK FACTOR MANAGEMENT in the stroke belt and
40% (Figure 1-216).17 This has per- Stroke prevention requires manage- among blacks and
sisted through recent decades and is ment of the major risk factors, including Mexican Americans.
particularly evident in black men. While hypertension, hyperlipidemia, diabetes h Hypertension is the
the mortality rate decreased in white mellitus, and tobacco use, as well as most common
women, white men, and black women antithrombotic therapy. A substantial modifiable risk factor
through all geographic regions, minimal portion of strokes can be prevented for stroke.
change was seen in black men in the with this approach.
East and West South Central regions.18
Globally, stroke is the second lead- Hypertension
ing cause of death.2 Between 1990 and Hypertension is the most common
2010, incidence and mortality have modifiable risk factor for stroke, affect-
decreased in high-income countries. ing about one-third of US adults over
However, no significant change has 20 years of age. Unfortunately, although
been seen in the incidence in low- and the majority of US adults with hyper-
middle-income countries, and the ab- tension are aware they have the
FIGURE 1-2 US stroke death rates from 2011 to 2013, adults 35 years of age and older, by county.
Reprinted from Centers for Disease Control and Prevention.16 cdc.gov/dhdsp/maps/national_maps/stroke_all.htm.

KEY POINT
h The recommended condition and are treated, only about 120 mm Hg had significantly reduced
blood pressure targets half have blood pressure that is con- risk of the primary composite end point
are less than trolled.2 Hypertension is particularly (myocardial infarction, acute coronary
140/90 mm Hg in prevalent in blacks, affecting 41% of syndrome, stroke, acute heart failure, or
patients with an men and 44% of women. High blood death from cardiovascular disease
ischemic stroke and pressures occur much earlier in life in events) than those randomly assigned
less than 130/80 mm Hg blacks than whites,2 and the higher sys- to a target less than 140 mm Hg.24 How-
in patients with a small tolic blood pressure explains about 50% ever, patients with prior stroke were ex-
vessel distribution of the excess risk of stroke in this ethnic cluded by design, and no difference was
ischemic stroke. group compared to whites.21 seen in stroke events during follow-up
What is the optimal goal blood pres- between the two treatment groups.24
sure for stroke prevention, and what is The significance of these findings is un-
the threshold for pharmacologic treat- clear for stroke primary prevention.
ment? These questions, which may be Most neurologists will be involved in
most relevant to primary care providers, the care of patients who have already
were addressed in an evidence-based had a stroke, and therefore recommen-
review and guideline recommendations dations from the AHA/American Stroke
from the Eighth Joint National Commit- Association (ASA) Guidelines for the Pre-
tee (JNC 8).22 The panel recommended vention of Stroke in Patients With Stroke
that individuals over 60 years of age or Transient Ischemic Attack8 are the
be treated for blood pressure of most relevant. The recommendations
150/90 mm Hg or more, whereas for are to initiate blood pressure therapy
those under 60 years of age, blood pres- for patients whose blood pressure re-
sure should be treated if greater than mains above 140/90 mm Hg or to re-
140/90 mm Hg (the latter based on ex- sume blood pressureYlowering therapy
pert opinion because of lack of evi- for those with hypertension, both of
dence).22 Those with diabetes mellitus which would be started several days
or chronic kidney disease should have after stroke onset. The specific target is
a goal blood pressure of less than individualized, but a reasonable goal is
140/90 mm Hg. The American Heart less than 140/90 mm Hg and, for those
Association (AHA) published an ad- with lacunar strokes, a target systolic
visory the same year as JNC 8, which blood pressure of less than 130 mm Hg.8
does not distinguish age as a factor in Which blood pressureYlowering strat-
the decision to treat blood pressure, egies are best? Several categories of
rather using the presence of stage 1 blood pressureYlowering medications
hypertension, ie, blood pressure that exist, but those that have been most
is 140 mm Hg to 159 mm Hg systolic extensively tested in the setting of
and 90 mm Hg to 99 mm Hg diastolic.23 secondary prevention of stroke include
What is important from both guidelines angiotensin-converting enzyme inhibi-
is the emphasis on lifestyle change, tors, thiazide diuretics, and calcium
such as exercise and diet, regardless of channel blockers. The AHA/ASA second-
age, diabetes mellitus, chronic kidney ary prevention guideline does not rec-
disease, or stage of hypertension. Of ommend a specific regimen because no
note, the Systolic Blood Pressure Inter- comparative effectiveness trials of these
vention Trial (SPRINT), published after strategies have been conducted. The best
the two guidelines previously de- evidence points toward treatment with
scribed, was stopped early because the diuretics and angiotensin-converting
group randomly assigned to intensive enzyme inhibitors, but consideration
blood pressure treatment to below should also be given to specific patient

KEY POINT
characteristics, such as extracranial ar- h Avoiding blood
tery disease, renal impairment, cardiac pressureYlowering
disease, and diabetes mellitus.8 medications that
Blood pressureYlowering medica- lead to variability is
tions that increase variability in mea- recommended.
surements between dosing should Treatment with
be avoided. Pooled analyses of the atenolol shows
United Kingdom Transient Ischemic more variability,
Attack (UK-TIA) aspirin trial and the while treatment
Anglo-Scandinavian Cardiac Outcomes with amlodipine is
associated with
TrialYBlood PressureYLowering Arm
less variability.
(ASCOT-BPLA) showed that visit-to-
visit variability in systolic blood pressure
increased the risk of stroke sixfold
(hazard ratio 6.22, 95% confidence
interval 4.16Y9.29, PG.0001), indepen-
dent of mean systolic blood pressure
(Figure 1-325). Similarly, maximum
systolic blood pressure was associated
with a 15-fold increased risk for stroke
(hazard ratio 15.01, 95% confidence
interval 6.56Y34.48, PG.0001).25 In these
trials, they found that amlodipine treat-
ment was associated with reduced
variability over time and that atenolol
increased variability. Atenolol treat-
ment led to the highest standard
deviation systolic blood pressure and
variability independent of the mean
systolic blood pressure, which also
corresponded to the highest hazard
ratio of stroke. By contrast, amlodipine
treatment was associated with lower
variability and a lower hazard ratio for
stroke (Figure 1-4).25 Another analysis
combining the ASCOT-BPLA with
Medical Research Council trials again
showed that atenolol treatment was
associated with increased variability
and higher risk of stroke compared FIGURE 1-3 Hazard ratios for risk of subsequent
stroke by deciles of standard deviation
with diuretics or calcium channel of systolic blood pressure over the
blockers.26 The conclusions of these first seven visits (baseline to 2 years) in the United
Kingdom Transient Ischemic Attack trial. Panel A
studies were that blood pressureY includes all patients in the trial, panel B excludes
lowering strategies should be chosen those with a past history of stroke, and panel C
excludes those with either a past history of stroke
based on the profile of both lowering or infarction on baseline CT brain imaging.
the mean blood pressure and reduc- CI = confidence interval.
ing variability (Case 1-1A).26 Reprinted with permission from Rothwell PM, et al,
Lifestyle modifications for blood Lancet.25 B 2010 Elsevier. thelancet.com/journals/lancet/
article/PIIS0140-6736(10)60308-X/abstract.
pressure lowering are recommended

FIGURE 1-4 Comparisons of amlodipine and atenolol by outcomes of stroke events.

The first row is mean systolic blood pressure (SBP), the second row is
standard deviation (SD) of SBP, the third row is variation independent of
mean (VIM) SBP, and the fourth row is average successive variability (ASV) of SBP.
Atenolol, but not amlodipine, is consistently in the top decile of SD SBP and VIM SBP,
corresponding to the highest hazard ratio of stroke.
Modified with permission from Rothwell PM, et al, Lancet.25 B 2010 Elsevier. thelancet.com/journals/
lancet/article/PIIS0140-6736(10)60308-X/abstract.

Case 1-1A
A 59-year-old black woman was seen in stroke clinic 1 month following
a right internal capsule infarct with residual left hemiparesis. She had a
history of hypertension and dyslipidemia. During her hospitalization, her
blood pressure was stable and she was continued on home atenolol 50 mg
2 times a day. She was also started on aspirin 325 mg/d for stroke prevention.
She continued these medications after she was discharged. On physical
examination, her body mass index (BMI) was 27 and her blood pressure was
150/92 mm Hg, but she stated that when she checks it at home, it ranges
from 120/60 mm Hg to, rarely, 160/90 mm Hg. She asked what her goal
blood pressure should be and when to be concerned.
Comment. Typically, a reasonable blood pressure goal is lower than
140/90 mm Hg poststroke, although a systolic goal of less than 130 mm Hg
is recommended for those with lacunar stroke. As the patient’s internal
capsule stroke is likely secondary to small vessel disease, the lower value
should be targeted. In addition, this patient has blood pressure
variability on atenolol, which increases her risk of stroke. Alternative
antihypertensives, such as amlodipine, should be considered. She should
also be counseled on lifestyle modifications.
and should include salt restriction; four groups of individuals deemed likely
weight loss; a diet rich in fruits, to benefit from moderate- or high-
vegetables, and low-fat dairy products potency statins were the following: (1)
(such as the Dietary Approaches to those with clinical atherosclerotic
Stop Hypertension [DASH] diet27 or cardiovascular disease, (2) those with
the Mediterranean diet28); regular aer- LDL-C higher than 190 mg/dL, (3) those
obic physical activity; and limited who are 40 to 75 years of age with dia-
alcohol consumption.8 betes mellitus and LDL-C 70 mg/dL to
189 mg/dL, and (4) those without clini-
Hyperlipidemia cal atherosclerotic cardiovascular dis-
The evaluation and treatment of hy- ease or diabetes mellitus who are 40 to
perlipidemia is such a critical part of 75 years of age with LDL-C 70 mg/dL to
stroke management that it is a quality 189 mg/dL and an estimated 10-year
metric monitored by the Centers for atherosclerotic cardiovascular disease
Medicare & Medicaid Services (CMS) risk of 7.5% or higher. These guide-
as well as The Joint Commission. The lines recommend estimating 10-year
cholesterol management guidelines atherosclerotic cardiovascular disease
published jointly by the American risk using a risk calculator (based on
College of Cardiology and the AHA in pooled cohort equations). The sec-
2013 provided a new perspective on ondary prevention guidelines also rec-
treatment with statins, with a move- ommend intensive statin therapy for
ment away from a specific low-density patients with stroke or transient ische-
lipoprotein cholesterol (LDL-C) target mic attack (TIA) presumed to be of
and toward a focus on treatment with atherosclerotic origin and initiation
statins that are likely to lower choles- of therapy for LDL-C 100 mg/dL or
terol by 50% or more (high-potency higher with or without evidence of
statins) or by 30% to 50% (moderate- clinical atherosclerotic cardiovascu-
potency statins) (Table 1-1).29 The lar disease.8 Secondary prevention

KEY POINT
h Atherosclerotic causes was of atherosclerotic origin and
of ischemic stroke or the TABLE 1-1 Low-, Moderate-, and whether LDL-C is higher than 100 mg/dL.8
High-Potency Statins In addition to statin therapy, both guide-
finding of a low-density
Recommended
lipoprotein level higher lines encourage a heart-healthy diet for
for Atherosclerotic
than 100 mg/dL should Cardiovascular Diseasea lowering cholesterol, which is described
be treated with a in more detail later in this article.
high-potency statin. In routine practice, many patients
b High-Potency Statin Therapy
(Daily dose lowers LDL-C by are reluctant to start statins because of
approximately Q50% on the high risk of myopathy or general
average) muscle pain, which varies from 7% to
Atorvastatin 40Y80 mg 29% in the literature.30 Statin-associated
myopathy is more likely with female
Rosuvastatin 20 or 40 mg
sex, older age, frailty, surgery, and mul-
b Moderate-Potency Statin tiple medications, among other factors,
Therapy (Daily dose lowers
so it is important to consider these risks
LDL-C by approximately 30%
to G50% on average) when initiating statins.31 Focusing on
women, an analysis of pooled patient
Atorvastatin 10 or 20 mg
level data from six statin trials showed
Rosuvastatin 5 or 10 mg that only one (Incremental Decrease in
Simvastatin 20Y40 mg Endpoints Through Aggressive Lipid
Lowering [IDEAL], atorvastatin 80 mg
Pravastatin 40 or 80 mg
versus simvastatin 20 mg to 40 mg) was
Lovastatin 40 mg associated with a significant interaction
Fluvastatin XL 80 mg between sex and rate of adverse effects.
For women on the high-dose atorvastatin,
Fluvastatin 40 mg
2 times a day 15.1% discontinued atorvastatin versus
4.6% on simvastatin, whereas in men,
Pitavastatin 2Y4 mg
8.3% discontinued atorvastatin versus
b Low-Potency Statin Therapy 4.1% on simvastatin. Multivariable
(Daily dose lowers LDL-C by modeling showed that increasing age,
G30% on average)
higher atorvastatin dose, and number
Simvastatin 10 mg of concomitant medications were pre-
Pravastatin 10Y20 mg dictive of statin discontinuation in both
sexes, and diabetes mellitus was predic-
Lovastatin 20 mg
tive of discontinuation in women, but
Fluvastatin 20Y40 mg not men.32
Pitavastatin 1 mg A helpful algorithm for management
of statin-association muscle symptoms
LDL-C = low-density lipoprotein
cholesterol. was published in 2015 30 in light of the
a
Modified with permission from 2013 cholesterol management guide-
Stone NJ, et al, J Am Coll Cardiol.29
B 2014 The Expert Panel Members. lines and high-potency statins for pre-
sciencedirect.com/science/article/pii/ vention of cardiovascular disease and
S0735109713060282.
stroke. If patients have muscle symp-
toms and a creatine kinase (CK) that is
greater than 4 times the upper limit
guidelines essentially concur with the of normal with or without rhabdomy-
American College of Cardiology/AHA olysis, then the statin should be dis-
recommendations but include consid- continued for 6 weeks and CK repeated.
eration of whether the stroke or TIA If the CK normalizes and symptoms

KEY POINT
are improved, a low dose of a second management of side effects. If patients h Intolerance to statins, a
high-potency statin or an alternate day experience severe myalgia that impacts common problem, can
or once or twice weekly dosing regimen their mobility, such as with walking, be addressed by
should be started. If patients have climbing stairs, or exercise, then the stopping the
muscle symptoms and a CK of less than statin should be discontinued to deter- medications, checking
4 times the upper limit of normal, then mine whether the symptoms improve. for muscle enzymes,
patients should discontinue the statin Serum CK should be collected and mea- and reducing the dose
for 2 to 4 weeks. At this point, a second sured to determine whether the statin upon reinitiation.
high-potency statin at the usual start- is causing myopathy. If rechallenge
ing dose is recommended. If symptoms with the statin is still not tolerated, low
reoccur with a second statin, then a or intermittent dosing with a potent or
third high-potency statin at low dose or efficacious statin should be used, and
a high-potency statin with alternate day with nonstatin therapies as adjuncts
or once or twice weekly dosing should as needed to achieve the LDL-C goal
be considered. Patients should be coun- (Case 1-1B). The European Atheroscle-
seled about the risk and successful rosis Society Consensus Panel Statement
Case 1-1B
Review of the records of the patient in Case 1-1A from her stroke hospitalization showed that her
carotid ultrasound showed 50% to 60% internal carotid artery stenosis bilaterally. Her high-density
lipoprotein was 40 mg/dL, and her total cholesterol was 240 mg/dL. A statin was not started at
discharge because she had a history of mild muscle aches on atorvastatin without impairment of
mobility. Her creatine kinase was measured by her primary care provider at the time and was normal.
Comment. With clinical atherosclerotic cerebrovascular disease, as demonstrated by her
extracranial carotid disease and small vessel distribution infarct, a moderate- or high-potency statin
is recommended. In addition, her atherosclerotic cardiovascular disease risk in 10 years was 52.8%
and her lifetime risk was 50% (Figure 1-5). Given the new event and risk that is significantly
higher than someone
her age with optimal
risk factors (2.7%), a
high-potency statin
should be reinitiated,
either atorvastatin or
rosuvastatin,
according to the
guidelines presented
in Table 1-1.
If rechallenge with
the statin leads to
recurrence of muscle
symptoms, then low
or intermittent
dosing with a potent
or efficacious statin
should be considered.
Lifestyle modifications, FIGURE 1-5 Risk calculator results for the patient in Case 1-1B based on age, race, sex, total
cholesterol, high-density lipoprotein cholesterol, treatment for high
such as diet and blood pressure, diabetes mellitus, and smoking.
exercise, should be ASCVD = atherosclerotic cardiovascular disease.
discussed as well.

KEY POINTS
h Disorders of glucose on Assessment, Aetiology, and Manage- progress toward a goal of less than 7%
metabolism are highly ment also specifically recommends in most adults.34 Although oral hypo-
prevalent in patients against the use of supplements, such as glycemic drugs are not recommended
with stroke. Patients coenzyme Q10 or vitamin D, to alleviate for secondary prevention, some sup-
with new-onset stroke muscle symptoms since no evidence of port exists for their use for patients with
or transient ischemic their benefits exists.30 In most settings, stroke. For example, the Prospective
attack should be neurologists will be conducting this Pioglitazone Clinical Trial in Macro-
screened for diabetes management in collaboration with the vascular Events (PROactive) showed that
mellitus with hemoglobin patient’s primary care provider or a among patients with a history of stroke,
A1c or an oral glucose highly specialized lipid clinic.
tolerance test.
pioglitazone was associated with a nearly
50% reduction in recurrent stroke
h Diabetes mellitus and Diabetes Mellitus and (hazard ratio 0.53; 95% confidence
metabolic syndrome are
Metabolic Syndrome interval 0.34Y0.85).35 The recently con-
key risk factors for
first-ever and recurrent Disorders of glucose metabolism are cluded Insulin Resistance Intervention
ischemic stroke; major risk factors for stroke, including After Stroke (IRIS) trial specifically fo-
therefore, management type 1 and type 2 diabetes mellitus and cused on secondary prevention of
for these conditions prediabetes (defined as hemoglobin A1c stroke in patients with insulin resistance
should include lifestyle of 5.7% to 6.4%). These disorders are and showed a 24% reduction of recur-
and pharmacologic highly prevalent in patients with stroke: rent stroke with pioglitazone (hazard
strategies to reduce the ratio 0.76; 95% confidence interval
28% have prediabetes, and 25% to
hemoglobin A1c to 0.62Y0.93; P=.007).36
45% have diabetes mellitus.8 In addi-
less than 7%.
tion, diabetes mellitus is independently Another important condition that
associated with a 60% risk (hazard ratio often includes impaired glucose me-
1.59; 95% confidence interval 1.07Y2.37) tabolism is metabolic syndrome, a risk
for recurrent stroke in the elderly.33 factor for stroke and cardiovascular
Therefore, the AHA/ASA secondary pre- disease that represents multiple com-
vention guideline recommends that ponents. It is diagnosed when three
patients with new-onset stroke or TIA of the following five risk factors are
should be screened for diabetes mel- present: (1) fasting plasma glucose of
litus with hemoglobin A1c or an oral 100 mg/dL or higher or the patient is
glucose tolerance test.8 Despite the prev- undergoing treatment for increased
alence and the major risk for recurrent glucose; (2) high-density lipoprotein
stroke with diabetes mellitus, the ideal cholesterol (HDL-C) of 40 mg/dL or less
targets for glucose control and the in men or 50 mg/dL or less in women or
treatments needed to reach these goals
the patient is undergoing treatment for
are not fully understood. The American
low HDL-C; (3) triglycerides of 150 mg/dL
Diabetes Association recommends that,
or higher or the patient is undergoing
for most patients with diabetes mellitus,
treatment for high triglycerides; (4)
the target hemoglobin A1c is less than
7%.34 It also recommends participation waist circumference 102 cm (40 in) or
in diabetes mellitus self-management higher in men or 88 cm (34.6 in) or
education and support as well as life- higher in women (may differ by ethnic-
style interventions as the first step to ity); (5) blood pressure 130 mm Hg or
management. Metformin, often initiated higher systolic or 85 mm Hg or higher
at a dose of 500 mg 2 times a day, is the diastolic, or the patient is undergoing
preferred initial pharmacologic agent. drug treatment for hypertension or
Repeat hemoglobin A1c is recommended antihypertensive drug treatment in a
after 3 months of treatment to track patient with a history of hypertension.2

KEY POINTS
The prevalence of metabolic syndrome tal admissions for stroke were reduced h Cigarette smoking is a
has been difficult to determine because by 14% in Arizona communities after significant risk factor, at
of varying definitions and variation by a public smoking ban, although a simi- least doubling the risk
ethnicity, but it appears to affect about lar decline was not seen in New York of stroke.
22% of the US population. The preva- State.44,45 Patients should be coun- h Nicotine replacement
lence is decreasing, perhaps because of seled on avoidance of environmental therapy, bupropion,
sources of smoke, and smokers in the and, in particular,
a decline in the components of blood
household should be counseled to quit varenicline are effective
pressure and triglyceride levels.2 Meta-
as well. treatments for smoking
bolic syndrome increases the risk of The risk of stroke is not as clear for cessation. While
stroke 1.5 to 23 times in women and other forms of tobacco and nicotine. electronic cigarettes
varies from no significant risk to a six- Few large-scale studies quantifying the may pose less potential
fold risk in men for studies published cerebrovascular or cardiovascular risk stroke risk than
through 2013.37 of smokeless tobacco exist, and risk is traditional cigarettes,
insufficient evidence
often difficult to distinguish from ciga-
exists to counsel
Tobacco Use rette use as much overlap exists. In a
patients to use
Tobacco use is a significant risk factor review of the available literature, the electronic cigarettes
for stroke as well as silent infarction.8 AHA policy statement on the impact as a primary form of
Current smokers have at least a dou- of smokeless tobacco on cardiovascular smoking cessation.
bled risk of stroke, with an apparent disease found that available data sug-
h Environmental exposure
dose-response relationship seen.38,39 gest no impact on hypertension and an to secondhand smoke
This has been seen in multiple unclear association with cardiovascular increases stroke risk by
population-based studies and across outcomes, with differences between as much as 30%
multiple age groups and ethnicities.38 studies likely due in part to the specific among nonsmokers.
In addition, a synergistic effect exists products used by participants.46 The h While the risk of stroke
with high blood pressure,40 and those Atherosclerosis Risk in Communities from smokeless tobacco
with hypertension should be aware (ARIC) registry showed 1.27 times in- products and electronic
of further increased risk. This risk is creased cardiovascular disease incidence cigarettes is less clear
very modifiable, with risk returning to (95% confidence interval 1.06Y1.52) than from cigarette
normal after 10 years of abstinence.38 among smokeless tobacco users, al- smoking, poststroke risk
Smoking cessation counseling should though this was not specific to stroke modification provides
be undertaken to reduce stroke risk, as it included myocardial infarction, an opportune time for
including offering available medica- stroke, cardiac revascularization, and counseling on cessation
cardiovascular/cerebrovascular death.47 from all forms of
tions. In one meta-analysis, all available
tobacco and nicotine.
medications for tobacco dependence Pooled results of studies on use of snus,
(forms of nicotine replacement therapy, the type of smokeless tobacco used in
bupropion, varenicline) were found to Sweden, did not find an increased risk
be superior to placebo in sustained of stroke.48 However, a meta-analysis
smoking cessation, and varenicline showed a relative risk of fatal stroke
was found superior to all treatments.41 in users of smokeless tobacco products
Practical counseling and identification of 1.40 (95% confidence interval
of social support have also been 1.28Y1.54).49 Although the risk of stroke
recommended as especially effective.42 is less clear with smokeless tobacco use
In addition, environmental exposure than in cigarette smoking, poststroke
to secondhand smoke has been iden- risk modification provides an oppor-
tified as a risk factor for stroke, in- tune time for counseling on cessation
creasing risk by as much as 30% among from all forms of tobacco.
nonsmokers.43 Community smoking New forms of nicotine delivery, such
bans have had variable results. Hospi- as electronic cigarettes (e-cigarettes) are

even less well understood. While more an independent role in stroke risk
than 400 brands of e-cigarettes exist, reduction. As large-scale nutritional
they all commonly contain a liquid studies are difficult to conduct, data
mixture of propylene glycol and nico- come primarily from observational or
tine housed in a cartridge or refillable cohort studies. Findings from the
tank. The device heats and aerosolizes Nurses’ Health Study and Health Pro-
the liquid, triggered by inhalation.50 fessionals Follow-Up Study have pro-
Because this method does not con- vided examples of dietary patterns
tain smoke, tar, or other chemicals, associated with lower risk of stroke.
e-cigarettes are marketed as a safe form Increased fruit and vegetable intake was
of nicotine delivery. Very little informa- associated with reduced stroke risk,
tion is available on the health effects of with the highest protective effect from
e-cigarettes; with less than 15 years on cruciferous and green leafy vegetables
the market, sufficient data do not exist and citrus fruits and juices.52 Each
to determine the risk of long-term additional one serving per day was
toxicity leading to cerebrovascular or associated with a 6% lower risk of
cardiovascular disease. The AHA policy ischemic stroke (relative risk, 0.94;
statement maintains that e-cigarette 95% confidence interval 0.90Y0.99;
regulation and health care screening P=.01).52 A single serving of caffein-
should be similar to other forms of ated or decaffeinated coffee decreased
tobacco.50 However, insufficient evi- stroke risk by approximately 10%.53
dence exists for counseling patients to However, daily servings of soda appear
use e-cigarettes as a primary form of to increase the risk of ischemic stroke,
smoking cessation (Case 1-1C).50 with 13% increase per serving per day
of sugar-sweetened soda and 7% in-
Diet and Nutrition creased risk of ischemic stroke per daily
Diet and nutrition are important to serving of low-calorie soda.53 An addi-
address in stroke prevention counsel- tional meta-analysis indicates lower
ing. Not only have dietary patterns been stroke risk with two to four or more than
associated with risk factor manage- five servings of fish per week compared
ment, but recent studies have indicated to less than one serving per week.54
Case 1-1C
The patient in Case 1-1A was a former smoker who quit 12 years earlier.
Many of her coworkers were smokers, and she joined them on their smoke
breaks to be social. Her husband continued to smoke but was trying to
quit. He asked about the use of electronic cigarettes (e-cigarettes).
Comment. The patient should be commended on smoking cessation and
encouraged to continue abstinence. However, the secondhand smoke she
was exposed to continued to increase her stroke risk. She should be
encouraged to avoid environmental exposure from coworkers, and her
husband should be encouraged to quit smoking or smoke outside the
house. Very little information is available on the long-term health effects of
e-cigarettes. While e-cigarettes may pose less potential stroke risk
compared to traditional cigarettes, insufficient evidence exists to counsel
her husband to use e-cigarettes as a primary form of smoking cessation,
and he should be encouraged to discuss forms of nicotine replacement
therapy, bupropion, or varenicline with his primary care provider.51

KEY POINT
Perhaps the most compelling evi- women and less than or equal to two h The Mediterranean diet
dence for the influence of nutrition 5-ounce servings for men) with meals, is associated with lower
specific to stroke risk comes from the is optional. The Mediterranean diet risk of stroke. It is
Prevención con Dieta Mediterránea with either olive oil or nut supplemen- characterized by high
(PREDIMED) study comparing the tation was associated with lower risk intake of olive oil, fruits
Mediterranean diet supplemented with of a composite primary end point of and vegetables, nuts,
either extra-virgin olive oil or mixed nuts myocardial infarction, stroke, or car- and whole grains;
compared to a low-fat control diet.28 diovascular death (hazard ratio 0.70, moderate intake of fish
The Mediterranean diet is characterized 95% confidence interval 0.54Y0.92 for and poultry; and low
by high intake of olive oil, fruits and the extra-virgin olive oil group and intake of dairy, red
and processed meats,
vegetables, nuts, and whole grains with hazard ratio 0.72, 95% confidence
and sweets.
moderate intake of fish and poultry and interval 0.54Y0.96 for the nut group).
low intake of dairy, red and processed Secondary end point analysis revealed
meats, and sweets (Table 1-255). Wine, a significant decline in stroke compared
consumed in moderation (less than or to the control diet (hazard ratio 0.61,
equal to one 5-ounce serving for 95% confidence interval 0.44Y0.86,
TABLE 1-2 Composition of the Healthy Mediterranean-Style and Healthy Vegetarian Eating
Patterns at the 2,000-Calorie Level, With Daily or Weekly Amounts From Food
Groups, Subgroups, and Componentsa
Healthy Mediterranean-Style Healthy Vegetarian

Food Group Eating Pattern Eating Pattern
Vegetables 2.5 cups per day 2.5 cups per day
Dark green 1.5 cups per week 1.5 cups per week
Red and orange 5.5 cups per week 5.5 cups per week
Legumes (beans and peas) 1.5 cups per week 3 cups per week
Starchy 5 cups per week 5 cups per week
Other 4 cups per week 4 cups per week
Fruits 2.5 cups per day 2 cups per day
Grains 6 oz per day 6.5 oz per day
Whole grains Q3 oz per day Q3.5 oz per day
Refined grains e3 oz per day e3 oz per day
Dairy 2 cups per day 3 cups per day
Protein foods 6.5 oz per day 3.5 oz per day
Seafood 15 oz per week None
Meats, poultry, eggs 26 oz per week 3 oz per week (eggs)
Nuts, seeds, soy products 5 oz per week 14 oz per week
Oils 27 g per day 27 g per day
Limit on calories for 260 kcal per day (13%) 290 kcal per day (15%)
other uses (% of calories)
a
Reprinted from U.S. Department of Health and Human Services and U.S. Department of Agriculture.55 health.gov/dietaryguidelines/
2015/guidelines/chapter-1/examples-of-other-healthy-eating-patterns/.

KEY POINTS
h Diet and nutrition can P=.005), but the difference in other sweetened beverages, and red meats.
affect not only risk end points was not significant.28 Lower These recommendations are consis-
factors such as risk of ischemic stroke with adherence tent with the DASH dietary pattern
hypertension and to the Mediterranean diet was confirmed and the AHA Diet.59
hyperlipidemia but also in the REGARDS cohort as well.56 Also of importance in lowering blood
stroke risk specifically. Additional findings show that extra- pressure is reduction of sodium intake.
The Dietary Approaches virgin olive oil in the context of the Lowering of blood pressure was seen
to Stop Hypertension Mediterranean diet may reduce atrial with sodium reduced to 2400 mg/d, with
diet is effective in fibrillation risk,57 and low adherence further improvement with a sodium in-
lowering blood pressure to the Mediterranean diet is associated take of only 1500 mg/d.60 A 1000 mg/d
and low-density
with increased large artery atheroscle- reduction of sodium intake reduces
lipoprotein, with
rotic stroke as well as worse clinical cardiovascular events by approximately
reduction of sodium
intake to 2400 mg/d or
presentation and outcome at dis- 30%, and higher sodium intake is asso-
less recommended for charge (as measured by the modified ciated with a greater risk of fatal and
those with hypertension. Rankin Score).58 nonfatal stroke and cardiovascular
In addition, diet is considered an disease. 59 High salt intake is also
h Obesity is an established
risk factor for ischemic
important strategy for risk factor independently associated with in-
stroke. With every management, in particular for choles- creased risk of stroke (relative risk 1.23,
1-unit increase in body terol and blood pressure lowering. The 95% confidence interval 1.06Y1.43;
mass index (about AHA/American College of Cardiology P=.007) (Case 1-1D).61
7 pounds), the risk for Guideline on Lifestyle Management to
ischemic stroke rises by Reduce Cardiovascular Risk was pub- Obesity
about 5%. lished in 2013. This evidence-based Being overweight or obese is highly
review showed that lowering saturated prevalent in the United States. Overall,
fat or total fat, or replacing saturated data from 2009 to 2012 showed that
fats or trans monounsaturated fats with 69% of US adults were overweight (body
monounsaturated or polyunsaturated mass index [BMI] higher than 25 kg/m2)
fats can successfully lower LDL-C.59 and 35% were obese (BMI of 30 kg/m2
The dietary pattern that is most effec- or higher).2 Obesity is an established
tive for lowering both LDL-C and blood risk factor for ischemic stroke, and epi-
pressure includes intake of vegetables, demiologic studies have shown that
fruits, whole grains, low-fat dairy prod- starting with a BMI of 20 kg/m2, for
ucts, poultry, fish, legumes, nontrop- every 1-unit increase in BMI (about
ical vegetable oils, and nuts while 7 pounds), the risk for ischemic stroke
limiting intake of sweets, sugar- rises by about 5%.62,63
Case 1-1D
The patient in Case 1-1A had been trying to lose weight over the past
5 years, following the Atkins diet. She asked about specific poststroke
dietary restrictions.
Comment. With hypertension, reduction of sodium intake is of
particular importance. To reduce blood pressure, sodium should be
reduced to 2400 mg/d, and the patient should be counseled that further
improvement in blood pressure has been seen with a sodium intake of
only 1500 mg/d. Although the Atkins diet has not been studied extensively
in stroke prevention, the Dietary Approaches to Stop Hypertension
(DASH) diet or Mediterranean diet (Table 1-2) should be encouraged
for risk factor reduction or stroke prevention, respectively.

The mechanism of cardiovascular dis- Physical Activity
ease and stroke risk with obesity is Exercise is defined as a “subset of phys-
linked to the adipose tissue as a repos- ical activity that is planned, structured,
itory of inflammatory cells, which may and repetitive and has as a final or an
contribute to insulin resistance and hy- intermediate objective the improvement
perglycemia and subsequently promote or maintenance of physical fitness,”
atherosclerosis.64 Some patients with whereas physical activity is “any bodily
obesity may be less likely to have an movement produced by skeletal mus-
adverse metabolic profile, and there- cles that results in energy expendi-
fore the recommendation is that once ture.”68 Physical activity, the focus of
obesity is identified, patients should this section, is defined by four di-
undergo additional testing for meta- mensions (mode or type, frequency,
bolic abnormalities, such as hypergly- duration, and intensity) and four com-
cemia, hypertriglyceridemia, cholesterol mon domains (occupational, domestic,
(especially low HDL), and inflammatory transportation, and leisure time). Al-
markers such as C-reactive protein.64 though physical activity is traditionally
The AHA/ASA secondary prevention reported as leisure time, it is important
guidelines specifically recommend to account for all domains.2 Physical
screening for obesity with determi- inactivity is defined as no sessions of
nation of BMI in all patients with TIA light/moderate or vigorous physical
or stroke. However, no evidence exists activity of more than 10 minutes’ dura-
to support weight loss among patients tion. The prevalence of physical in-
with stroke or TIA for secondary pre- activity is reported to be 28.5% of men
vention, although weight loss is ben- and 31.5% of women and increases with
eficial for improving cardiovascular age (about 50% of those older than
risk factors.8 75 years of age).2 In general, systematic
After stroke, a high prevalence of im- reviews and meta-analyses have shown
paired glucose tolerance and diabetes that engaging in physical activity can
mellitus exists in stroke survivors, which reduce the risk of stroke or mortality
may, in part, be related to physiologic by 25% to 30%.38
changes in muscle in hemiparetic limbs. For those who have survived a
Along with the loss of skeletal muscle stroke, engaging in physical activity
mass and less physical activity, stroke can be challenging because of residual
survivors may have a predisposition to hemiparesis, sensory impairment, ne-
weight gain. In addition, the hemiparetic glect, dyscoordination, spasticity, cog-
muscle may undergo accumulation of nitive dysfunction, or aphasia. As
intramuscular fat and a switch from impairments impact the ability for self-
slow-twitch to fast myosin heavy chain care in up to 40% of stroke survivors
fibers, which rely on anaerobic me- and may impose activity limitations
tabolism.65,66 This type of metabolism and restrictions, it is not surprising that
predisposes to oxidative injury and in- a large proportion of stroke survivors
flammation that leads to glucose intol- ultimately choose a sedentary lifestyle,
erance (insulin resistance). Physical even if they are able to participate in
activity, in addition to being a weight physical activity.69 Unfortunately, no
loss strategy, has important effects on trials of physical activity/exercise pro-
insulin resistance that are nearly imme- grams have been shown to reduce
diate by suppressing fatty acidYinduced the risk of a recurrent stroke, but
insulin resistance and inflammation in studies have shown that exercise has
skeletal muscle.67 a positive effect on risk factors such as

hypertension, arterial function, and stroke survivors in both the acute and
insulin response.69 rehabilitation phases are outlined
Evidence-based recommendations in Table 1-3,70 including inpatient
for physical activity and exercise for and outpatient exercise therapy. The
TABLE 1-3 Summary of Exercise/Physical Activity Recommendations for Stroke Survivorsa,b
Prescriptive Guidelines:
Setting/Mode of Exercise Goals/Objectives Frequency/Intensity/Time
Hospitalization and early
convalescence (acute phase)
Low-level walking, self-care Prevent deconditioning, hypostatic Approximately 10Y20 beats/min
activities pneumonia, orthostatic increases in resting heart rate (HR);
intolerance, and depression; rate of perceived exertion (RPE)
Intermittent sitting or standing
evaluate cognitive and motor e11 (6Y20 scale); frequency and
Seated activities deficits; stimulate balance duration as tolerated, using an
and coordination interval or work-rest approach
Range-of-motion activities,
motor challenges
Inpatient and outpatient exercise
therapy or rehabilitation
Aerobic Increase walking speed and 40Y70% oxygen uptake (VO2)
efficiency; improve exercise reserve or HR reserve; 55Y80% HR
Large-muscle activities
tolerance (functional capacity); maximum; RPE 11Y14 (6Y20 scale)
(eg, walking, graded
increase independence in
walking, stationary cycle 3Y5 days per week; 20- to
activities of daily living (ADLs);
ergometry, arm ergometry, 60-minute session (or multiple
reduce motor impairment
arm-leg ergometry, functional 10-minute sessions); 5Y10 minutes
and improve cognition; improve
activities with seated of warm-up and cool-down
vascular health and induce
exercises, if appropriate) activities; complement with
other cardioprotective benefits
pedometers to increase lifestyle
(eg, vasomotor reactivity,
physical activity
decrease cardiovascular risk)
Muscular strength/endurance Increase muscle strength and 1Y3 sets of 10Y15 repetitions of
endurance; increase ability to 8Y10 exercises involving the major
Resistance training of upper perform leisure time and muscle groups at 50Y80% of
and lower extremities, occupational activities and 1 repetition maximum; 2Y3 days
trunk using free weights, ADLs; reduce cardiac demands per week; resistance gradually
weight-bearing or partial (ie, rate-pressure product) increased over time as
weight-bearing activities, during lifting or carrying objects tolerance permits
elastic bands, spring by increasing muscular strength,
coils, pulleys thereby decreasing the percentage
Circuit training of maximal voluntary contractions
that a given load now represents
Functional mobility
Flexibility Increase range of motion of Static stretches; hold for

involved segments; prevent 10Y30 seconds
Stretching (trunk, upper
contractures; decrease risk
and lower extremities) 2Y3 days per week (before or
of injury; increase ADLs
after aerobic or strength training)
Continued on page 31

TABLE 1-3 Summary of Exercise/Physical Activity Recommendations for Stroke Survivorsa,b
Continued from page 30
Prescriptive Guidelines:
Setting/Mode of Exercise Goals/Objectives Frequency/Intensity/Time
Neuromuscular Improve balance, skill reacquisition, Use as a complement to aerobic,
quality of life, and mobility; muscular strength/endurance
Balance and coordination decrease fear of falling; improve training, and stretching activities;
activities
level of safety during ADLs 2Y3 days per week
Tai chi
Yoga
Recreational activities
using paddles/sport balls
to challenge hand-eye
coordination
Active-play video gaming
and interactive
computer games
a
Modified from Gordon NF, et al, Circulation.70 B 2004 American Heart Association, Inc. circ.ahajournals.org/content/109/16/2031.long.
b
Reprinted with permission from Billinger SA, et al, Stroke.69 B 2014 American Heart Association, Inc. stroke.ahajournals.org/content/
45/8/2532.long.
recommendations include aerobic, intensity aerobic exercise per week, KEY POINT
muscular strength/endurance, flexibil- with sessions lasting an average of h Patients with stroke
should engage in three
ity, and neuromuscular activities, as 40 minutes. The guideline also recom-
to four sessions of
well as the frequency, intensity, and mends referral to a comprehensive,
moderate- to
duration of activities that can provide behaviorally oriented program for those vigorous-intensity
multiple benefits for stroke survivors willing and able to initiate physical activ- aerobic exercise per
(Case 1-1E).69 The AHA/ASA second- ity, and, for those with disabilities, week, with sessions
ary prevention guideline recommends supervision by a health care professional lasting an average of
that patients engage in three to four such as a physical therapist or cardiac 40 minutes.
sessions of moderate- to vigorous- rehabilitation expert is reasonable.8
Case 1-1E
On neurologic examination, the patient in Case 1-1A had left facial
asymmetry and 5-/5 strength throughout her left hemibody. Her gait was
slow, but not spastic. She had completed a course of physical therapy
and continued to use a cane for long distances. She asked about activity
restrictions or recommendations.
Comment. This stroke survivor has minimal weakness but some
limitations in mobility after reaching her physical therapy goals. She should
be encouraged to pursue safe mobility by increasing her walking in the
community, starting with 10 minutes at a time and increasing to 20 to
60 minutes at a time, 3 to 5 days per week. This aerobic exercise could also
include stationary cycle ergometry, arm ergometry, arm-leg ergometry, or
functional activities with seated exercises (Table 1-3). Other recommended
neuromuscular exercises include tai chi, yoga, or recreational activities using
paddles/sport balls to challenge hand-eye coordination.69

To increase physical activity in stroke women, with a higher apnea-hypopnea

survivors, health professionals are en- index threshold (higher than 25) nec-
couraged to incorporate behavioral essary to increase the risk of stroke
counseling on physical activity into visits. in women.74
Although primary care was the target The rate of sleep apnea after stroke
audience for recommendations by is high, although it is unclear if dis-
Berra and colleagues,71 strategies for ordered breathing precedes stroke or
integrating physical activity counseling develops poststroke. One meta-analysis
into clinical practice are important in demonstrated that sleep apnea is seen
stroke prevention clinics as well, espe- in 72% of patients with stroke or TIA if
cially for patients with TIAs. This starts the threshold of an apnea-hypopnea
with making “physical activity a vital index higher than 5 is used; 63% had an
sign at each clinic visit.”71 apnea-hypopnea index higher than 10,
and 38% of patients with stroke or TIA
EMERGING RISK FACTORS have severe sleep apnea with an apnea-
FOR STROKE hypopnea index higher than 20.75 An
Additional risk factors have been iden- apnea-hypopnea index higher than 10
tified in recent years, although their was seen more commonly in men than
contribution to stroke risk is less well women (65% versus 48%, P=.001) and
defined. Treatment of the following was more common in patients with
conditions may further reduce risk of recurrent stroke (74% versus 57%,
stroke, but additional research is re- P=.013). Central apnea was only seen
quired to fully understand best man- in 7%.75 The presence and severity
agement practices in stroke patients. of sleep apnea are independent of
stroke subtype.76
Sleep Apnea OSA has been associated with higher
Sleep apnea is measured by the apnea- poststroke mortality and worse func-
hypopnea index, which identifies the tional outcome.8 However, it is unclear
number of respiratory events per hour, if treatment with continuous positive
including cessations in breathing and airway pressure (CPAP) improves cere-
reductions in air flow. Sleep apnea has brovascular outcomes or reduces re-
been linked to increased risk of incident current stroke.8 Early treatment with
stroke. Although obstructive sleep ap- CPAP in the acute period has not shown
nea (OSA) has been associated with significant benefit.8 When patients were
hypertension across sex and ethnicities, followed for 7 years poststroke, those
some evidence exists of an independent who did not use CPAP had a higher rate
risk of stroke.72 In an observational of recurrent stroke than those who did
cohort study over about 3 years, sleep (32% versus 14%, P=.021).77 In addition,
apnea defined as an apnea-hypopnea well-established stroke risk factors such
index of 5 or higher increased the risk as hypertension and atrial fibrillation re-
of stroke or death from all causes, in- spond favorably to the successful treat-
dependent of other cerebrovascular ment of sleep apnea.78
risk factors (hazard ratio, 1.97; 95% con- With the prevalence of OSA post-
fidence interval 1.12Y3.48; P=.01).73 stroke and the potential for improved
While increased risk of stroke alone outcomes and secondary stroke pre-
was seen in men, with 6% increased vention, the American Academy of
risk with each point in the apnea- Sleep Medicine recommends screening
hypopnea index from 5 to 25, this via polysomnography in patients with
association may not be as strong in stroke and TIA with symptoms of sleep

KEY POINTS
apnea.79 Unfortunately, identification multiethnic Northern Manhattan Study h Obstructive sleep apnea
of who should receive screening is dif- (NOMAS), elevated lipoprotein (a) has been linked to
ficult as symptoms such as sleepiness levels (both continuous and dichoto- increased risk of
and signs such as BMI and neck cir- mized into higher than 30 mg/dL) were incident stroke, higher
cumference are not adequate predic- associated with incident ischemic poststroke mortality,
tors of OSA in patients with stroke.8 stroke after adjustment for other rele- and worse
Therefore, polysomnography should vant risk factors. When considering functional outcome.
be considered with a high suspicion of gender and race/ethnicity, the strongest Polysomnography
apnea, even without typical signs or association after adjustment for risk should be considered
symptoms, especially in men because factors was in men and in blacks.85 with high suspicion of
apnea, even without
of possible increased correlation With emerging risk factors such as
typical signs
with stroke.8 lipoprotein (a) and a lack of studies
or symptoms.
showing that treatment reduces the risk
Lipoprotein (a) for cardiovascular disease, it is difficult h Lipoprotein (a) is a
lipoprotein that has
Lipoprotein (a) is a lipoprotein that has to know whether to test for lipoprotein
been associated with
been associated with both atheroscle- (a) levels and in whom. It has been
both atherosclerosis and
rosis and thrombogenesis. The mole- shown that lipoprotein (a) levels can be thrombogenesis. While
cule is attached to the LDL receptor decreased with niacin by 30% to 35%, it has been associated
and bears structural similarity to fibrates up to 20%, aspirin 10% to 20%, with increased stroke
plasminogen.80 The levels of this mol- and estrogens 37%, but statins inconsis- risk in children,
ecule appear to vary by gender, race, tently lower lipoprotein (a). Nephrotic association in adults
and genotype of the APOA gene.81 syndrome and end-stage renal disease, is less clear.
While elevated levels of lipoprotein for example, lead to a threefold increase,
(a) appear to be strongly associated likely through increased biosynthesis
with arterial ischemic stroke in chil- and from reduced catabolism, respec-
dren,82 the association in adults is less tively.86 To date, the AHA/ASA second-
certain. A 2007 meta-analysis suggested ary prevention guidelines do not offer
that elevated lipoprotein (a) levels were recommendations for when to test lipo-
associated with stroke events in case- protein (a). In a comprehensive review
control studies (odds ratio 2.39; 1.57Y3.63) of the pathophysiology, impact of ge-
and prospective cohort studies (relative netic and nongenetic factors on lev-
risk 1.22; 1.04Y1.43) but not nested els, and the epidemiologic associations
case-control studies (odds ratio 1.04; of lipoprotein (a) with coronary artery
0.6Y1.8).83 The lack of significance with disease and stroke, Kostner and col-
nested case-control studies could have leagues86 suggest the following:
been because of smaller sample size & Patients with premature
and lack of power. The authors of this cardiovascular disease or stroke
analysis suggest that different methods without evident risk factors should
of measuring lipoprotein (a) may also have lipoprotein (a) levels
contribute to some of the uncertainty.83 measured at least once
Studies that have been conducted since & Patients with intermediate
the meta-analysis have continued to cardiovascular disease risk based
show an association. In the biethnic on risk scores should be tested for
Atherosclerosis Risk in Communities lipoprotein (a), and if the level is
(ARIC) cohort, elevated lipoprotein (a) higher than 50 mg/dL, the patient
levels higher than 300 mcg/mL were would be shifted to a higher
associated with a higher incidence of risk category
ischemic stroke in blacks and white & Patients with recurrent or rapidly
women, but not white men.84 In the progressive vascular disease

KEY POINT
h In patients without a and various recognized risk Multiple trials have evaluated the
cardioembolic source, factors should have lipoprotein combination of dipyridamole and aspi-
aspirin monotherapy at (a) levels checked and rin in secondary stroke prevention. The
doses of 50 mg to repeatedly monitored if on European Stroke Prevention Study 2
325 mg is an appropriate drug treatment (ESPS-2) compared the combination of
strategy for secondary & Patients with familial hyper- dipyridamole 200 mg and aspirin 25 mg
stroke prevention. cholesterolemia, genetic 2 times a day to placebo, with a 37% risk
dyslipidemia or low HDL-C, or reduction of subsequent stroke and a
genetic defects of hemostasis or 23% risk reduction when compared
homocysteine metabolism should to aspirin 25 mg 2 times a day.89 While
be tested for lipoprotein (a) bleeding is not significantly increased
& Patients without evident with this combination, headache and
cardiovascular disease but gastrointestinal symptoms have limited
elevated cardiovascular disease its use significantly. However, AHA/ASA
risk, such as a greater than guidelines recommend consideration
10% 10-year risk of fatal or of aspirin alone or combination aspi-
nonfatal coronary heart disease rin and dipyridamole for secondary
as per the risk calculator stroke prevention.8
should also be tested Clopidogrel has been compared to
for lipoprotein (a) aspirin alone in the Clopidogrel Versus
Aspirin in Patients at Risk of Ischaemic
ANTIPLATELET THERAPY Events (CAPRIE) trial, which enrolled
In patients without a cardioembolic over 19,000 patients with stroke, myo-
source, antiplatelet therapy is a main- cardial infarction, or peripheral vascular
stay of stroke prevention, consistently disease.90 The combined outcome of
reducing risk of recurrent stroke across ischemic stroke, myocardial infarction,
studies. The cheapest and most widely and vascular death was significantly lower
available option is aspirin, which has with clopidogrel (5.32% versus 5.83%,
been studied for stroke prevention in relative risk reduction 8.7%, 95% confi-
doses ranging from 50 mg to 1500 mg. dence interval 0.3%Y16.5%, P=.043),
Across placebo-controlled trials of aspi- although the study was not designed
rin for secondary stroke prevention, re- to determine effectiveness in secondary
duction of stroke was approximately stroke prevention. Subgroup analysis of
15% (relative risk, 95% confidence inter- patients entering the trial because of
val 6%Y23%).87 Meta-analysis of head- stroke did not show a significant differ-
to-head trials of aspirin dose found no ence in vascular outcomes. Clopidogrel
significant difference in stroke prevention is a reasonable alternative to aspirin
between low-dose aspirin (lower than or combination aspirin/dipyridamole,
75 mg) and higher doses (75 mg or eg, in patients who are allergic to
higher).88 However, pooled results from aspirin or have other indications for
studies without direct comparison of clopidogrel use.8
doses show a smaller effect with a The combination of aspirin and clo-
dose lower than 75 mg/d. Aspirin mono- pidogrel has been compared to clo-
therapy at doses of 50 mg/d to 325 mg/d pidogrel alone in patients with TIA or
is an appropriate strategy for secondary ischemic stroke in the Management of
stroke prevention and is recommended Atherothrombosis With Clopidogrel
by the AHA/ASA guidelines for the in High-Risk Patients With Recent Tran-
Prevention of Stroke in Patients with sient Ischaemic Attack or Ischaemic
Stroke and TIA.8 Stroke (MATCH) trial,91 and to aspirin

alone in patients with cardiovascular cumulative relative risk reduction of
disease or risk factors in the Clopidogrel vascular events of 80%.93
for High Atherothrombotic Risk and
Ischemic Stabilization, Management, REFERENCES
and Avoidance (CHARISMA) trial.92 1. O’Carroll CB, Barrett KM. Cardioembolic
Neither study showed significant ben- stroke. Continuum (Minneap Minn) 2017;
23(1 Cerebrovascular Disease):XXYXX.
efit of combination therapy in primary
composite outcome or secondary out- 2. Mozaffarian D, Benjamin EJ, Go AS, et al.
Heart Disease and Stroke StatisticsV2016
comes. In MATCH, the risk of major Update: a report from the American Heart
hemorrhage was significantly increased Association. Circulation 2016;133(4):e38Ye60.
in the combination group, with a 1.3% doi:10.1161/CIR.0000000000000350.
absolute increase in life-threatening 3. Howard VJ, McClure LA, Meschia JF, et al.
bleeding.91 Additionally, the subgroup High prevalence of stroke symptoms among
persons without a diagnosis of stroke or
analysis of patients in CHARISMA with
transient ischemic attack in a general
prior stroke showed increased bleed- population: the REasons for Geographic
ing risk but no statistically significant And Racial Differences in Stroke (REGARDS)
benefit of combination therapy.92 There- study. Arch Intern Med 2006;166(18):
1952Y1958. doi:10.1001/archinte.
fore, combination clopidogrel and aspi-
166.18.1952.
rin is not routinely recommended for
4. Dhamoon MS, Sciacca RR, Rundek T, et al.
secondary stroke prevention per AHA/ Recurrent stroke and cardiac risks after
ASA guidelines.8 first ischemic stroke: the Northern
Unfortunately, no clinical trials have Manhattan Study. Neurology
evaluated the best therapy in patients 2006;66(5):641Y646. doi:10.1212/
01.wnl.0000201253.93811.f6.
who have had an event while receiving
aspirin. Additionally, no evidence exists 5. Feng W, Hendry RM, Adams RJ. Risk of
recurrent stroke, myocardial infarction, or
that increasing the dose of aspirin pro- death in hospitalized stroke patients.
vides additional benefit. AHA/ASA rec- Neurology 2010;74(7):588Y593. doi:10.1212/
ommendations note that no adequate WNL.0b013e3181cff776.
evidence exists to provide guidelines 6. Fang MC, Coca Perraillon M, Ghosh K, et al.
for prevention of recurrent stroke in Trends in stroke rates, risk, and outcomes in
the United States, 1988 to 2008. Am J Med
patients who have had an event while
2014;127(7):608Y615. doi:10.1016/
on aspirin.8 j.amjmed.2014.03.017.
7. Hong KS, Yegiaian S, Lee M, et al. Declining
CONCLUSION stroke and vascular event recurrence
rates in secondary prevention trials over
Management of the risk factors discussed
the past 50 years and consequences for
has the ultimate goal of reducing the current trial design. Circulation 2011;
risk of recurrent stroke. However, these 123(19):2111Y2119. doi:10.1161/
prevention strategies will also provide CIRCULATIONAHA.109.934786.
a benefit for other cardiovascular dis- 8. Kernan WN, Ovbiagele B, Black HR, et al.
eases and dementia, especially in those Guidelines for the prevention of stroke in
patients with stroke and transient ischemic
patients with stroke onset at younger attack: a guideline for healthcare
ages. A comprehensive modeling of risk professionals from the American Heart
factor management suggests that if Association/American Stroke Association.
individuals with initial stroke or TIA Stroke 2014;45(7):2160Y2236. doi:10.1161/
STR.0000000000000024.
undertake five proven prevention strat-
9. Lee BI, Nam HS, Heo JH, et al. Yonsei Stroke
egies, including dietary modification,
Registry. Analysis of 1,000 patients with
exercise, aspirin, a statin, and an antihy- acute cerebral infarctions. Cerebrovasc Dis
pertensive agent, it could result in a 2001;12(3):145Y151.

10. Sealy-Jefferson S, Wing JJ, Sánchez B, et al. and injuries in 188 countries, 1990-2013: a
Age- and ethnic-specific sex differences in systematic analysis for the Global Burden of
stroke risk. Gend Med 2012;9(2):121Y128. Disease Study 2013. Lancet 2015;386(9995):
doi:10.1016/j.genm.2012.02.002. 743Y800. doi:10.1016/S0140-6736(15)60692-4.
11. Seshadri S, Beiser A, Kelly-Hayes M, et al. 21. Howard G, Cushman M, Kissela BM, et al.
The lifetime risk of stroke: estimates from Traditional risk factors as the underlying
the Framingham Study. Stroke 2006; cause of racial disparities in stroke: lessons
37(2):345Y350. doi:10.1161/ from the half-full (empty?) glass. Stroke
01.STR.0000199613.38911.b2. 2011;42(12):3369Y3375. doi:10.1161/
12. Reeves MJ, Bushnell CD, Howard G, et al. STROKEAHA.111.625277.
Sex differences in stroke: epidemiology, 22. James PA, Oparil S, Carter BL, et al. 2014
clinical presentation, medical care, and evidence-based guideline for the
outcomes. Lancet Neurol 2008;7(10):915Y926. management of high blood pressure in adults:
doi:10.1016/S1474-4422(08)70193-5. report from the panel members appointed
13. Howard VJ, Kleindorfer DO, Judd SE, et al. to the Eighth Joint National Committee
Disparities in stroke incidence contributing (JNC 8). JAMA 2014;311(5):507Y520.
to disparities in stroke mortality. doi:10.1001/jama.2013.284427.
Ann Neurol 2011;69(4):619Y627. 23. Go AS, Bauman MA, Coleman King SM, et al.
doi:10.1002/ana.22385. An effective approach to high blood pressure
14. Kleindorfer DO, Khoury J, Moomaw CJ, et al. control: a science advisory from the
Stroke incidence is decreasing in whites but American Heart Association, the American
not in blacks: a population-based estimate College of Cardiology, and the Centers
of temporal trends in stroke incidence from for Disease Control and Prevention. J Am
the Greater Cincinnati/Northern Kentucky Coll Cardiol 2014;63(12):1230Y1238.
Stroke Study. Stroke J Cereb Circ 2010; doi:10.1016/j.jacc.2013.11.007.
41(7):1326Y1331. doi:10.1161/
24. SPRINT Research Group, Wright JT Jr,
STROKEAHA.109.575043.
Williamson JD, et al. A randomized trial of
15. Morgenstern LB, Smith MA, Lisabeth LD, intensive versus standard blood-pressure
et al. Excess stroke in Mexican Americans control. N Engl J Med 2015;373(22):
compared with non-Hispanic Whites: the 2103Y2116. doi:10.1056/NEJMoa1511939.
Brain Attack Surveillance in Corpus Christi
25. Rothwell PM, Howard SC, Dolan E, et al.
Project. Am J Epidemiol 2004;160(4):
Prognostic significance of visit-to-visit
376Y383. doi:10.1093/aje/kwh225.
variability, maximum systolic blood pressure,
16. Centers for Disease Control and Prevention. and episodic hypertension. Lancet
Stroke death rates, total population 35+. 2010;375(9718):895Y905. doi:10.1016/
cdc.gov/dhdsp/maps/national_maps/ S0140-6736(10)60308-X.
stroke_all.htm. Updated June 24, 2015.
26. Rothwell PM, Howard SC, Dolan E, et al.
Accessed November 29, 2016.
Effects of beta blockers and calcium-channel
17. Howard G, Anderson R, Johnson NJ, et al. blockers on within-individual variability in
Evaluation of social status as a contributing blood pressure and risk of stroke. Lancet
factor to the stroke belt region of the Neurol 2010;9(5):469Y480. doi:10.1016/
United States. Stroke 1997;28(5):936Y940. S1474-4422(10)70066-1.
doi:10.1161/01.STR.28.5.936.
27. Appel LJ, Moore TJ, Obarzanek E, et al. A
18. Gillum RF, Kwagyan J, Obisesan TO. Ethnic clinical trial of the effects of dietary patterns
and geographic variation in stroke mortality on blood pressure. DASH Collaborative Research
trends. Stroke 2011;42(11):3294Y3296. Group. N Engl J Med 1997;336(17):1117Y1124.
doi:10.1161/STROKEAHA.111.625343. 28. Estruch R, Ros E, Salas-Salvadó J, et al. Primary
prevention of cardiovascular disease with a
19. Krishnamurthi RV, Feigin VL, Forouzanfar
Mediterranean diet. N Engl J Med 2013;368(14):
MH, et al. Global and regional burden of
1279Y1290. doi:10.1056/NEJMoa1200303.
first-ever ischaemic and haemorrhagic
stroke during 1990-2010: findings from the 29. Stone NJ, Robinson JG, Lichtenstein AH,
Global Burden of Disease Study 2010. Lancet et al. 2013 ACC/AHA guideline on the
Glob Health 2013;1(5):e259Ye281. treatment of blood cholesterol to reduce
doi:10.1016/S2214-109X(13)70089-5. atherosclerotic cardiovascular risk in adults:
a report of the American College of
20. Global Burden of Disease Study 2013 Cardiology/American Heart Association
Collaborators. Global, regional, and national Task Force on Practice Guidelines. J Am Coll
incidence, prevalence, and years lived with Cardiol 2014;63(25 pt B):2889Y2934.
disability for 301 acute and chronic diseases doi:10.1016/j.jacc.2013.11.002.

30. Stroes ES, Thompson PD, Corsini A, et al. 41. Mills EJ, Wu P, Lockhart I, et al. Comparisons
Statin-associated muscle symptoms: impact of high-dose and combination nicotine
on statin therapyVEuropean Atherosclerosis replacement therapy, varenicline, and
Society Consensus Panel Statement on bupropion for smoking cessation: a
Assessment, Aetiology and Management. systematic review and multiple treatment
Eur Heart J 2015;36(27):1012Y1022. meta-analysis. Ann Med 2012;44(6):588Y597.
doi:10.1093/eurheartj/ehv043. doi:10.3109/07853890.2012.705016.
31. Tomlinson SS, Mangione KK. Potential 42. 2008 PHS Guideline Update Panel, Liaisons,
adverse effects of statins on muscle. Phys and Staff. Treating tobacco use and
Ther 2005;85(5):459Y465. dependence: 2008 update U.S. Public Health
Service Clinical Practice Guideline executive
32. Hsue PY, Bittner VA, Betteridge J, et al.
summary. Respir Care 2008;53(9):
Impact of female sex on lipid lowering,
1217Y1222.
clinical outcomes, and adverse effects in
atorvastatin trials. Am J Cardiol 2015;115(4): 43. Malek AM, Cushman M, Lackland DT, et al.
447Y453. doi:10.1016/j.amjcard.2014.11.026. Secondhand smoke exposure and stroke: the
Reasons for Geographic and Racial
33. Kaplan RC, Tirschwell DL, Longstreth WT Jr,
Differences in Stroke (REGARDS) study.
et al. Vascular events, mortality, and
Am J Prev Med 2015;49(6):e89Ye97.
preventive therapy following ischemic stroke
doi:10.1016/j.amepre.2015.04.014.
in the elderly. Neurology 2005;65(6):835Y842.
doi:10.1212/01.wnl.0000176058.09848.bb. 44. Herman PM, Walsh ME. Hospital admissions
for acute myocardial infarction, angina,
34. Chamberlain JJ, Rhinehart AS, Shaefer CF Jr,
stroke, and asthma after implementation of
Neuman A. Diagnosis and management of
Arizona’s comprehensive statewide smoking
diabetes: synopsis of the 2016 American
ban. Am J Public Health 2011;101(3):
Diabetes Association Standards of Medical
491Y496. doi:10.2105/AJPH.2009.179572.
Care in Diabetes. Ann Intern Med 2016;
164(8):542Y552. doi:10.7326/M15-3016. 45. Juster HR, Loomis BR, Hinman TM, et al.
Declines in hospital admissions for acute
35. Wilcox R, Bousser MG, Betteridge DJ, et al.
myocardial infarction in New York state after
Effects of pioglitazone in patients with type
implementation of a comprehensive smoking
2 diabetes with or without previous stroke:
ban. Am J Public Health 2007;97(11):
results from PROactive (PROspective
2035Y2039. doi:10.2105/AJPH.2006.099994.
pioglitAzone Clinical Trial In macroVascular
Events 04). Stroke 2007;38(3):865Y873. 46. Piano MR, Benowitz NL, Fitzgerald GA, et al.
doi:10.1161/01.STR.0000257974.06317.49. Impact of smokeless tobacco products on
cardiovascular disease: implications for
36. Kernan WN, Viscoli CM, Furie KL, et al.
policy, prevention, and treatment: a policy
Pioglitazone after ischemic stroke or transient
statement from the American Heart
ischemic attack. N Engl J Med 2016;374(14):
Association. Circulation 2010;122(15):1520Y1544.
1321Y1331. doi:10.1056/NEJMoa1506930.
doi:10.1161/CIR.0b013e3181f432c3.
37. Bushnell C, McCullough LD, Awad IA, et al.
47. Yatsuya H, Folsom AR, ARIC Investigators.
Guidelines for the prevention of stroke in
Risk of incident cardiovascular disease
women: a statement for healthcare
among users of smokeless tobacco in the
professionals from the American Heart
Atherosclerosis Risk in Communities (ARIC)
Association/American Stroke Association.
study. Am J Epidemiol 2010;172(5):600Y605.
Stroke 2014;45(5):1545Y1588. doi:10.1161/
doi:10.1093/aje/kwq191.
01.str.0000442009.06663.48.
38. Meschia JF, Bushnell C, Boden-Albala B, et al. 48. Hansson J, Galanti MR, Hergens MP, et al.
Guidelines for the primary prevention of stroke: Snus (Swedish smokeless tobacco) use and
a statement for healthcare professionals from risk of stroke: pooled analyses of incidence
the American Heart Association/American and survival. J Intern Med 2014;276(1):
Stroke Association. Stroke 2014;45(12): 87Y95. doi:10.1111/joim.12219.
3754Y3832. doi:10.1161/STR.0000000000000046. 49. Boffetta P, Straif K. Use of smokeless
39. Shah RS, Cole JW. Smoking and stroke: tobacco and risk of myocardial infarction
the more you smoke the more you stroke. and stroke: systematic review with
Expert Rev Cardiovasc Ther 2010;8(7): meta-analysis. BMJ 2009;339:b3060.
917Y932. doi:10.1586/erc.10.56. doi:10.1136/bmj.b3060.
40. Nakamura K, Barzi F, Lam TH, et al. 50. Bhatnagar A, Whitsel LP, Ribisl KM, et al.
Cigarette smoking, systolic blood pressure, Electronic cigarettes: a policy statement
and cardiovascular diseases in the Asia-Pacific from the American Heart Association.
region. Stroke 2008;39(6):1694Y1702. Circulation 2014;130(16):1418Y1436.
doi:10.1161/STROKEAHA.107.496752. doi:10.1161/CIR.0000000000000107.

51. Burns DM. Epidemiology of Group. N Engl J Med 2001;344(1):3Y10.

smoking-induced cardiovascular disease. doi:10.1056/NEJM200101043440101.
Prog Cardiovasc Dis 2003;46(1):11Y29.
61. Strazzullo P, D’Elia L, Kandala NB, Cappuccio
doi:10.1016/S0033-0620(03)00079-3.
FP. Salt intake, stroke, and cardiovascular
52. Joshipura KJ, Ascherio A, Manson JE, et al. disease: meta-analysis of prospective studies.
Fruit and vegetable intake in relation to risk BMJ 2009;339:b4567. doi:10.1136/
of ischemic stroke. JAMA 1999;282(13): bmj.b4567.
1233Y1239. doi:10.1001/jama.282.13.1233.
62. Rexrode KM, Hennekens CH, Willett WC,
53. Bernstein AM, de Koning L, Flint AJ, et al. et al. A prospective study of body mass
Soda consumption and the risk of stroke in index, weight change, and risk of stroke in
men and women. Am J Clin Nutr 2012;95(5): women. JAMA 1997;277(19):1539Y1545.
1190Y1199. doi:10.3945/ajcn.111.030205. doi:10.1001/jama.1997.03540430051032.
54. Chowdhury R, Stevens S, Gorman D, et al. 63. Kurth T, Gaziano JM, Berger K, et al. Body
Association between fish consumption, long mass index and the risk of stroke in men. Arch
chain omega 3 fatty acids, and risk of Intern Med 2002;162(22):2557Y2562.
cerebrovascular disease: systematic review doi:10.1001/archinte.162.22.2557.
and meta-analysis. BMJ 2012;345:e6698.
doi:10.1136/bmj.e6698. 64. Kernan WN, Inzucchi SE, Sawan C, et al.
Obesity: a stubbornly obvious target for
55. U.S. Department of Health and Human
stroke prevention. Stroke 2013;44(1):278Y286.
Services and U.S. Department of Agriculture.
doi:10.1161/STROKEAHA.111.639922.
Chapter 1: key elements of healthy eating
patterns. In: 2015-2020 Dietary guidelines 65. Ryan AS, Dobrovolny CL, Smith GV, et al.
for Americans. 8th edition. health.gov/ Hemiparetic muscle atrophy and increased
dietaryguidelines/2015/guidelines/chapter-1/ intramuscular fat in stroke patients. Arch
examples-of-other-healthy-eating-patterns/. Phys Med Rehabil 2002;83(12):1703Y1707.
Published December 2015. Accessed doi: 10.1053/apmr.2002.36399.
November 29, 2016.
66. De Deyne PG, Hafer-Macko CE, Ivey FM, et al.
56. Tsivgoulis G, Psaltopoulou T, Wadley VG, Muscle molecular phenotype after stroke is
et al. Adherence to a Mediterranean diet associated with gait speed. Muscle Nerve
and prediction of incident stroke. Stroke 2004;30(2):209Y215. doi:10.1002/mus.20085
2015;46(3):780Y785. doi:10.1161/
67. Schenk S, Horowitz JF. Acute exercise
STROKEAHA.114.007894.
increases triglyceride synthesis in skeletal
57. Martı́nez-González MÁ, Toledo E, Arós F, muscle and prevents fatty acidYinduced
et al. Extravirgin olive oil consumption insulin resistance. J Clin Invest 2007;
reduces risk of atrial fibrillation: the 117(6):1690Y1698. doi:10.1172/JCI30566.
PREDIMED (Prevención con Dieta
Mediterránea) trial. Circulation 2014; 68. Caspersen CJ, Powell KE, Christenson GM.
130(1):18Y26. doi:10.1161/ Physical activity, exercise, and physical
fitness: definitions and distinctions for
CIRCULATIONAHA.113.006921.
health-related research. Public Health Rep
58. Tuttolomondo A, Casuccio A, Buttà C, et al. 1985;100(2):126Y131.
Mediterranean diet in patients with acute
ischemic stroke: relationships between 69. Billinger SA, Arena R, Bernhardt J, et al.
Mediterranean diet score, diagnostic Physical activity and exercise recommendations
subtype, and stroke severity index. for stroke survivors: a statement for
Atherosclerosis 2015;243(1):260Y267. healthcare professionals from the American
doi:10.1016/j.atherosclerosis.2015.09.017. Heart Association/American Stroke
Association. Stroke 2014;45(8):2532Y2553.
59. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/
doi:10.1161/STR.0000000000000022.
ACC guideline on lifestyle management to
reduce cardiovascular risk: a report of the 70. Gordon NF, Gulanick M, Costa F, et al.
American College of Cardiology/American Physical activity and exercise
Heart Association Task Force on Practice recommendations for stroke survivors: an
Guidelines. circ.ahajournals.org/content/129/ American Heart Association scientific
25_suppl_2/S76.full.pdf?download=true. statement from the Council on Clinical
Published June 24, 2014. Accessed Cardiology, Subcommittee on Exercise,
November 29, 2016. Cardiac Rehabilitation, and Prevention;
60. Sacks FM, Svetkey LP, Vollmer WM, et al. the Council on Cardiovascular Nursing;
Effects on blood pressure of reduced dietary the Council on Nutrition, Physical Activity,
sodium and the Dietary Approaches to and Metabolism; and the Stroke Council.
Stop Hypertension (DASH) diet. Circulation 2004;109(16):2031Y2014.
DASH-Sodium Collaborative Research doi:0.1161/01.CIR.0000126280.65777.A4.

71. Berra K, Rippe J, Manson JE. Making physical 83. Smolders B, Lemmens R, Thijs V. Lipoprotein
activity counseling a priority in clinical practice: (a) and stroke: a meta-analysis of observational
the time for action is now. JAMA 2015;314(24): studies. Stroke 2007;38(6):1959Y1966.
2617Y2618. doi:10.1001/jama.2015.16244. doi:10.1161/STROKEAHA.106.480657.
72. Nieto FJ, Young TB, Lind BK, et al. 84. Ohira T, Schreiner PJ, Morrisett JD, et al.
Association of sleep-disordered breathing, Lipoprotein(a) and incident ischemic stroke:
sleep apnea, and hypertension in a large the Atherosclerosis Risk in Communities
community-based study. Sleep Heart Health (ARIC) study. Stroke 2006;37(6):1407Y1412.
Study. JAMA 2000;283(14):1829Y1836. doi:10.1161/01.STR.0000222666.21482.b6.
doi:10.1001/jama.283.14.1829.
85. Boden-Albala B, Kargman DE, Lin IF, et al.
73. Yaggi HK, Concato J, Kernan WN, et al. Increased stroke risk and lipoprotein(a) in
Obstructive sleep apnea as a risk factor for a multiethnic community: the Northern
stroke and death. N Engl J Med 2005; Manhattan Stroke Study. Cerebrovasc
353(19):2034Y2041. doi:10.1056/ Dis 2010;30(3):237Y243. doi:10.1159/
NEJMoa043104. 000319065.
74. Redline S, Yenokyan G, Gottlieb DJ, et al. 86. Kostner KM, März W, Kostner GM. When
Obstructive sleep apnea-hypopnea and should we measure lipoprotein(a)? Eur
incident stroke: the sleep heart health study. Heart J 2013;34(42):3268Y3276. doi:10.1093/
Am J Respir Crit Care Med 2010;182(2): eurheartj/eht053.
269Y277. doi:10.1164/rccm.200911-1746OC. 87. Johnson ES, Lanes SF, Wentworth CE 3rd,
75. Johnson KG, Johnson DC. Frequency of sleep et al. A metaregression analysis of the
apnea in stroke and TIA patients: a meta-analysis. dose-response effect of aspirin on stroke.
J Clin Sleep Med 2010;6(2):131Y137. Arch Intern Med 1999;159(11):1248Y1253.
doi:10.1001/archinte.159.11.1248.
76. Brown DL, Mowla A, McDermott M, et al.
Ischemic stroke subtype and presence of 88. Antithrombotic Trialists’ Collaboration.
sleep-disordered breathing: the BASIC sleep Collaborative meta-analysis of randomised
apnea study. J Stroke Cerebrovasc Dis trials of antiplatelet therapy for prevention
2015;24(2):388Y393. doi:10.1016/ of death, myocardial infarction, and stroke
in high risk patients. BMJ 2002;324(7329):
j.jstrokecerebrovasdis.2014.09.007.
71Y86. doi:10.1136/bmj.324.7329.71.
77. Martı́nez-Garcı́a MA, Campos-Rodrı́guez F, 89. Diener H, Cunha L, Forbes C, et al. European
Soler-Cataluña JJ, et al. Increased incidence Stroke Prevention Study. 2. Dypyridamole and
of nonfatal cardiovascular events in stroke acetylsalicylic acid in the secondary prevention
patients with sleep apnoea: effect of CPAP of stroke. J Neurol Sci 1996;143(1-2):1Y13.
treatment. Eur Respir J 2012;39(4):906Y912. doi:10.1016/S0022-510X(96)00308-5.
doi:10.1183/09031936.00011311.
90. CAPRIE Steering Committee. A randomised,
78. Culebras A. Sleep apnea and stroke. Curr blinded, trial of clopidogrel versus aspirin in
Neurol Neurosci Rep 2015;15(1):503. patients at risk of ischaemic events (CAPRIE).
doi:10.1007/s11910-014-0503-3. CAPRIE Steering Committee. Lancet 1996;
348(9038):1329Y1339. doi: 10.1016/
79. Epstein LJ, Kristo D, Strollo PJ Jr, et al. Clinical
S0140-6736(96)09457-3.
guideline for the evaluation, management
and long-term care of obstructive sleep 91. Diener HC, Bogousslavsky J, Brass LM, et al.
apnea in adults. J Clin Sleep Med Aspirin and clopidogrel compared with
2009;5(3):263Y276. clopidogrel alone after recent ischaemic
stroke or transient ischaemic attack in
80. Loscalzo J. Lipoprotein(a). A unique risk high-risk patients (MATCH): randomised,
factor for atherothrombotic disease. double-blind, placebo-controlled trial.
Arteriosclerosis 1990;10(5):672Y679. Lancet 2004;364(9431):331Y337. doi:10.1016/
doi:10.1161/01.ATV.10.5.672. S0140-6736(04)16721-4.
81. Schreiner PJ, Heiss G, Tyroler HA, et al. Race 92. Bhatt DL, Fox KAA, Hacke W, et al.
and gender differences in the association of Clopidogrel and aspirin versus aspirin alone
Lp(a) with carotid artery wall thickness. The for the prevention of atherothrombotic
Atherosclerosis Risk in Communities (ARIC) study. events. N Engl J Med 2006;354(16):
Arterioscler Thromb Vasc Biol 1996;16(3): 1706Y1717. doi:10.1056/NEJMoa060989.
471Y478. doi: 10.1161/01.ATV.16.3.471. 93. Hackam DG, Spence JD. Combining multiple
82. Sultan SM, Schupf N, Dowling MM, et al. approaches for the secondary prevention
Review of lipid and lipoprotein(a) abnormalities of vascular events after stroke. Stroke
in childhood arterial ischemic stroke. Int J 2007;38(6):1881Y1885. doi:10.1161/
Stroke 2014;9(1):79Y87. doi:10.1111/ijs.12136. STROKEAHA.106.475525.

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INTRODUCTION overall prevalence of 2.6% in those

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FIGURE 1-1 Prevalence of stroke by age and sex.

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FIGURE 1-4 Comparisons of amlodipine and atenolol by outcomes of stroke events.

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Healthy Mediterranean-Style Healthy Vegetarian

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TABLE 1-3 Summary of Exercise/Physical Activity Recommendations for Stroke Survivorsa,b

Flexibility Increase range of motion of Static stretches; hold for

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To increase physical activity in stroke women, with a higher apnea-hypopnea

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51. Burns DM. Epidemiology of Group. N Engl J Med 2001;344(1):3Y10.

38 ContinuumJournal.com February 2017

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