GAH!!! the STUPIDITY/LAZINESS that is displayed here.
http://annals.org/article.aspx?articleid=1881123
Abstract
Description: In
February 2014, the American Heart Association/American Stroke
Association released their first guideline focused on stroke prevention
in women. This new guideline highlights unique risk factors for stroke
in women, including oral contraception and hormone therapy, and
pregnancy-associated disorders, such as preeclampsia, that may have
long-lasting consequences on a woman's health. It also addresses
hypertension; atrial fibrillation; migraine headache with aura; and the
epidemiology of types of stroke, such as aneurysmal subarachnoid
hemorrhage and cerebral vein thrombosis, that are predominant in women.
Methods: Members of a multidisciplinary expert panel searched, reviewed, and critiqued relevant English-language literature published between 1990 and May 2013. The panel devised evidence tables and developed recommendations using American Heart Association guideline procedures and levels of evidence.
Recommendations: This synopsis of the guideline summarizes the evidence about risk factors for stroke in women and suggests prevention strategies. It also describes the new recommendations relevant to identifying and treating hypertensive disorders in pregnancy that increase risk for stroke.
Methods: Members of a multidisciplinary expert panel searched, reviewed, and critiqued relevant English-language literature published between 1990 and May 2013. The panel devised evidence tables and developed recommendations using American Heart Association guideline procedures and levels of evidence.
Recommendations: This synopsis of the guideline summarizes the evidence about risk factors for stroke in women and suggests prevention strategies. It also describes the new recommendations relevant to identifying and treating hypertensive disorders in pregnancy that increase risk for stroke.
Sex
differences are increasingly recognized in many areas of medicine, and
stroke is no exception. An estimated 6.8 million persons in the United
States have had a stroke, most of whom are women (3.8 million) (1).
At the time of stroke, women are older and more likely to be living
alone and have worse premorbid status than men. After stroke, they also
are more likely to be institutionalized and have a poorer recovery and
worse quality of life than men (2–6).
There
are many unique risk factors for stroke in women, such as pregnancy and
pregnancy complications, hormonal contraception, and hormone therapy
for menopause symptoms. Several other risk factors are more common in
women than in men, including hypertension, atrial fibrillation, migraine
headache with aura, and depression and psychosocial stress (Table).
With these issues in mind, we developed a sex-specific guideline that
consolidates recommendations specific to stroke prevention in women from
primary and secondary prevention guidelines (7–8) and emphasizes stroke-specific issues in more detail than previously published cardiovascular prevention guidelines (9).
The
American Heart Association Manuscript Oversight Committee and the
Scientific Statement Oversight Committee of the Stroke Council approved
the topic areas for the guideline and the expert panel that developed
and wrote the guideline. Panel members had expertise on stroke in women
and stroke prevention. They represented many disciplines, including
neurology, neurosurgery, neurocritical care, neuroscience and research
on sex differences, internal medicine, obstetrics and gynecology,
cardiology, pharmacology, nursing, epidemiology, and public policy.
We
assigned topic areas to 1 primary reviewer and 1 or 2 secondary
reviewers selected from the panel. These reviewers developed search
terms to identify literature relevant to their topic area. Members of
the writing group then searched PubMed, MEDLINE, the Cochrane Library,
CardioSource, and EMBASE for English-language literature published
between 1990 and 15 May 2013.
The
reviewers scanned the search results, selected papers relevant to their
topic, and abstracted data from selected studies to create evidence
tables. All members of the panel then reviewed evidence tables and
developed recommendations using the American Heart Association's ratings
for class of recommendation and level of evidence (10).
The Stroke Council leadership committee and the Scientific Statements
Oversight Committee coordinated extensive peer review of the guideline,
and the Science Advisory and Coordinating Committee approved the final
draft.
Hypertension, the most modifiable risk factor for stroke, is more prevalent in women than men (11).
Hypertension is more often poorly controlled in older women; only 23%
of women versus 38% of men older than 80 years have a blood pressure
less than 140/90 mm Hg (12).
There is currently no evidence that antihypertensive treatments
differentially affect blood pressure response or stroke prevention by
sex, but many trials of antihypertensive agents do not report
sex-specific analysis for efficacy or adverse effect profiles. Moreover,
there are major evidence gaps about appropriate drug choices, treatment
resistance, adherence, and hormone-dependent and -independent
approaches to blood pressure treatment by sex (13).
Sex
differences in atrial fibrillation include a higher prevalence and a
higher associated risk for thromboembolic events in women (14).
The effect of this epidemiology has translated into the development of
risk scores for patients with atrial fibrillation, with an additional
point given for female sex in the CHA2DS2-VASc (congestive
heart failure/left ventricular dysfunction, hypertension, age ≥75 years,
diabetes mellitus, stroke/transient ischemic attack/thromboembolism,
vascular disease, age 65 to 74 years, sex category) score (15).
Therefore, we recommend use of risk stratification tools that account
for age- and sex-specific differences in the incidence of stroke. Women,
particularly those older than 75 years, should be actively screened for
atrial fibrillation with pulse rate measurement and electrocardiography
as appropriate (class I; level of evidence B). We also suggest
antiplatelet therapy for women with lone atrial fibrillation who are
aged 65 years or younger (13).
Women are 4 times more likely than men to have migraine headache (16).
Although the absolute risk for stroke associated with migraine headache
is low, the association between migraine headache with aura and stroke
seems strongest in women younger than 55 years (17–18). The frequency of migraine headache may also be associated with stroke (19).
We
therefore suggest reducing the frequency of migraine headache as a
possible strategy to reduce the risk for stroke, although there is no
evidence that specific treatment strategies (for example,
calcium-channel blockers, β-blockers, and antiepileptic drugs) reduce
the risk for stroke (13).
Given a synergistic relationship between smoking and migraine headache
with aura, we recommend smoking cessation treatments and counseling for
persons who smoke and have migraine headache. Finally, we encourage
clinicians to caution women with migraine headache about the use of oral
contraceptives (13).
The
use of oral contraceptives is a risk factor for stroke in young women,
increasing the risk from 1.4- to 2.0-fold compared with that of women
who do not use these agents (13).
The absolute risk is low—approximately 2 events per 10 000 women per
year with the use of the lowest-dose formulation, according to a recent
study from Denmark (20).
The risk for stroke among women using oral contraceptives increases
exponentially from 3.4 per 100 000 women aged 15 to 19 years to 64.4 per
100 000 women aged 45 to 49 years (20).
Factors that could further increase risk for stroke include prior
thromboembolic events, hypertension, cigarette smoking, hyperlipidemia,
diabetes, and obesity. Accordingly, we recommend identifying women with
such risk factors and increasing efforts to manage modifiable risk
factors in women who use oral contraceptives.
The
guideline also addresses prothrombotic mutations and biomarkers that
increase the risk for stroke in a synergistic manner. Studies show that
markers of endothelial dysfunction, such as von Willebrand factor and
ADAMTS13 (a disintegrin and metalloproteinase with the thrombospondin
type 1 repeat 13), increase the risk for stroke more than 10-fold in
women who use oral contraceptives compared with those who do not (21).
Although many prothrombotic mutations increase the risk for stroke in
women using oral contraceptives, we do not recommend screening for these
mutations before starting oral contraceptive therapy because of their
low prevalence in otherwise healthy women, especially in the absence of a
positive family history (13).
Additional
research is needed to better characterize the risk for hemorrhagic
stroke with oral contraceptive use, focusing on older women who may use
these agents until menopause, members of underrepresented minority
groups, genetic makeup, and parity. The study of clinically available
biomarkers, such as von Willebrand factor, is warranted in broader
populations of women.
Menopause,
particularly younger age at menopause, and risk for stroke may be
related, but evidence defining such a relationship is inconsistent.
Whether natural versus surgical menopause is associated with risk for
stroke is also unclear. However, the use of hormone therapy in
postmenopausal women is a unique risk factor for stroke in women.
In
general, hormone therapy is associated with an increased risk for
stroke and is not recommended for primary or secondary prevention of
this condition. Many gaps remain in research about the magnitude of
harms and tradeoffs between benefits and risks of hormone therapy. These
gaps concern treatment of subgroups of women who are at high risk for
stroke after menopause; treatment of women who are early in the peri- or
postmenopause period; and the optimum timing, dosage, type, and route
of administration that could enhance vascular health (13).
Several
cohort studies and a meta-analysis have identified depression and
psychosocial stress as factors that increase the risk for incident
stroke by 25% to 45% in women (22–24).
The odds ratios across studies that included both men and women are
similar to those of studies that included only men or only women, making
it difficult to state conclusively that women with these conditions
have a higher risk for stroke than men. More research is needed to
understand the subgroups of women at risk, such as those who are treated
versus not, and the method of determining depression and psychosocial
stress (13).
We
advise maintaining a healthy weight, eating a healthy diet, abstinence
from smoking, regular physical activity, moderate alcohol intake, and
activities and interventions aimed at achieving or maintaining normal
blood pressure and cholesterol and blood glucose levels. The guideline
highlights the risk for stroke in several high-risk conditions,
including obesity, physical inactivity, and the metabolic syndrome, but
found few data that suggest these conditions increase risk for stroke
disproportionately in women.
However,
a recent meta-analysis of studies involving more than 750 000 persons
and more than 12 000 strokes found that diabetic women have a 27%
greater relative risk for stroke than diabetic men (25).
The mechanisms underlying this increased risk are unknown but may be
related to a more adverse cardiovascular risk profile during the
prediabetic phase in women than men (25).
This meta-analysis provides further evidence that recognition of risk
factors for stroke, especially those that may disproportionately
increase risk in women, is critical to prevent stroke. Healthy lifestyle
interventions, including regular physical activity, such diets as the
Dietary Approaches to Stop Hypertension, abstinence from smoking,
moderate alcohol consumption (13),
and recognition and treatment of diabetes, are important. Until
sex-specific strategies are tested, recommendations for stroke
prevention in terms of healthy lifestyle interventions remain the same
for men and women.
Women
with symptomatic carotid stenosis (recent ischemic stroke or transient
ischemic attack ipsilateral to the carotid stenosis) may be less likely
to receive carotid endarterectomy than men (26).
Whether benefits and risks of carotid angioplasty and stenting differ
between women and men is not known. Data from CREST (Carotid
Revascularization Endarterectomy Versus Stenting Trial) showed that
women randomly assigned to angioplasty and stenting had a higher
proportion of periprocedural events than men and a possible interaction
between the treatment assignment and sex (P = 0.064) (27).
There
are clear sex differences in carotid artery plaque (women have less
inflammatory features) and a higher risk for periprocedural
complications with endarterectomy for asymptomatic stenosis. However,
evidence to suggest that women with symptomatic or asymptomatic carotid
stenosis should be treated medically versus surgically (with
endarterectomy or coronary artery stenting) or differently from men is
currently lacking (13).
Therefore, the guideline recommendations are the same for both sexes.
There are many gaps in our understanding of the sex-specific treatment
of carotid disease, so future trials are needed to determine whether
surgery is superior to aggressive medical management in women with
symptomatic carotid stenosis.
There
is no convincing evidence to suggest that a particular antiplatelet
therapy or dosage of such therapy is more or less beneficial in women
than men, but protection from aspirin may be specific to certain
vascular diseases on the basis of sex. For example, the results of the
WHS (Women's Health Study), a trial of 100 mg of aspirin every other day
versus placebo, showed that aspirin did not reduce the risk for
myocardial infarction or death from cardiovascular causes but did
decrease stroke events (relative risk, 0.83 [95% CI, 0.69 to 0.99]),
especially ischemic stroke (relative risk, 0.76 [CI, 0.63 to 0.93]) (28).
A meta-analysis of aspirin and primary prevention showed that women
seem to be protected from stroke, whereas men are protected from
myocardial infarction (29).
However, the ATT (Antithrombotic Trialists’) Collaboration study
reported no evidence of a sex difference in any of the vascular outcomes
after adjustment for multiple comparisons (30).
Consistent
with other published recommendations, our guideline suggests
considering aspirin in women older than 65 years if blood pressure is
controlled and the benefit of preventing ischemic stroke or myocardial
infarction outweighs the risk for gastrointestinal bleeding and
hemorrhagic stroke (13).
Whether a woman younger than 65 years may benefit from aspirin could be
addressed if a sex-specific risk score were available.
The risk for stroke during pregnancy is fairly low (about 34 per 100 000 deliveries) (31),
but risk is highest in the postpartum period. Although the traditional
definition of a postpartum time frame is 6 weeks, a recent study showed
that thrombotic events may occur up to 12 weeks after birth (32).
Suspicion for a postpartum stroke or vasculopathy (the posterior
reversible encephalopathy syndrome or the reversible cerebral
vasoconstriction syndrome) or cerebral venous thrombosis should be
heightened for women who develop new-onset headache, blurred vision, or
seizures or any new neurologic signs or symptoms during the postpartum
period (13).
Preeclampsia
occurs in approximately 5% of pregnancies. It is defined as high blood
pressure in pregnancy associated with proteinuria (urinary protein
excretion ≥300 mg/24 h) or thrombocytopenia, impaired liver function,
progressive renal insufficiency, pulmonary edema, or new-onset cerebral
or visual disturbances (33).
The American Congress of Obstetricians and Gynecologists (formerly the
American College of Obstetricians and Gynecologists) published an
updated guideline (released after our guideline was in production) that
changed the criteria for preeclampsia to include women without
proteinuria if one of the other multisystem features is present (33).
Because
of evidence that a history of preeclampsia is associated with a 2-fold
risk for stroke and a 4-fold risk for hypertension later in life, we
recommend documenting preeclampsia as a risk factor (class IIa; level of
evidence C) (13).
Our intent is to increase awareness that women with a history of
preeclampsia would probably benefit from lifestyle change and early
assessment of cardiovascular risk and interventions. Although the
evidence for an association between preeclampsia and later hypertension
with attendant risk for stroke is clear, the current gap in knowledge is
identifying which women with preeclampsia will have these
complications. More research is needed to understand biomarkers or other
characteristics that might identify the women at highest risk (13).
Another
new recommendation is to consider treating women with a systolic blood
pressure between 150 and 159 mm Hg or a diastolic blood pressure between
100 and 109 mm Hg of new onset during pregnancy (class IIa; level of
evidence B). This recommendation differs from that of the guideline of
the American Congress of Obstetricians and Gynecologists, which
recommends only treating patients with a blood pressure greater than
160/110 mm Hg (33).
Our new recommendation is based on evidence that treatment of mild to
moderately elevated blood pressure in pregnancy is associated with a 50%
reduction in risk for severe hypertension (relative risk, 0.5 [CI, 0.41
to 0.61]) (34).
New
studies or reanalyses of existing data using the new definition of
preeclampsia would be useful to assess the benefit of treating mild to
moderately elevated blood pressure during pregnancy. Although safe and
effective antihypertensive medications can be used during pregnancy,
risk to the fetus must also be considered (13).
These
guidelines provide recommendations for the prevention of stroke in
women, emphasizing risk factors that are unique or more prevalent in
women. Of note, we recognize many gaps in the literature that limit the
ability to provide strong (level of evidence A), sex-specific
recommendations. Some stroke-specific risk scores, such as the
Framingham risk score for stroke (35),
take sex into account but do not allow calculation of risk in persons
younger than 54 years. Goals for our guideline included identifying
unique risk factors and facilitating the development of new sex-specific
tools for scoring risk for stroke.
We
suggest that a more accurate assessment of risk for stroke is possible
if events that occur in young adulthood known to increase this risk in
later life, such as preeclampsia, are documented. In addition, risks
unique to women (use of oral contraceptives and hormone therapy) and
established risk factors that are more prevalent in older women
(hypertension and atrial fibrillation) should be recognized. We hope
that this guideline will spur additional research to determine the best
approaches to stroke prevention for both men and women. (proof once again that prevention is the answer to everything)
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