Sex Is Not a Risk Factor in Outcome When a Stroke Unit
Treats the Patient
Valeria Caso, MD, PhD; Maurizio Paciaroni, MD
See related article, p 367.
here are ongoing debates on whether sex is a risk factor
for stroke outcome. It is known that females tend to have
worse outcomes compared with males when stroke onset is
later in life.1,2 Moreover, females generally have a higher burden from atrial fibrillation translating into more thromboembolic events and more severe strokes, compared with males.3,4
Likewise, females of all ages have more hypertension, and
their risk for stroke from diabetes mellitus is higher when compared with males: relative risk 2.28 (confidence interval 95%
1.93–2.69) versus 1.83 (confidence interval 95% 1.60–2.08).5
As well, a recent systematic meta-analysis of sex-specific risk
factors for stroke reported that females could have increased
stroke risk because of hypertensive disorder in pregnancy for
ischemic stroke, late menopause and gestational hypertension for hemorrhagic stroke, and oophorectomy, hypertensive
disorder in pregnancy, preterm delivery, and stillbirth for any
stroke. However, male-specific risk factors increasing stroke
risk include medical androgen deprivation therapy for ischemic and any stroke and erectile dysfunction for any stroke.6
Do these sex-specific risk factors and the differing burdens
from stroke risk factors depending on the sex of the patient
influence outcomes?
To this regard, Hametner et al7 analyzed data from the
VISTA (Virtual International Stroke Trials Archive) aiming to
investigate sex-specific differences in poststroke outcome in
individual-level data pooled from randomized controlled trials. Using novel matching techniques, they approximated a
randomized experiment accounting for covariates that differed
between the sexes. The 2 hypotheses included investigating,
first, whether the natural course of stroke was different between
males and females without recombinant tissue-type plasminogen activator treatment after adjustment for relevant prognostic
factors using a similar adjustment for relevant prognostic factors, and whether the response to recombinant tissue-type plasminogen activator differed between males and females.
The authors reported that in nonthrombolysed patients, ordinal analysis of modified Rankin Scale, adjusting for stroke- and
sex-related prognostic factors, suggested comparable outcomes
for females and males (odds ratio 0.96, 95% confidence interval 0.85–1.06). Furthermore, females and males responded
comparably to recombinant tissue-type plasminogen activator,
irrespective of the outcome definition of modified Rankin Scale
(ordinal: P interaction =0.46, relative excess risk because of
interaction =0).
The results from this elegant and sophisticated statistical
model evidence that thrombolysis and stroke unit care guarantee optimal stroke outcome, regardless of sex and sex-specific
risk factors.
However, the results cannot be interpreted as if they
reflected the real picture throughout the world. That is, the outcomes were undoubtedly influenced by the fact that all patients
received the best treatment available, and moreover, these were
not limited by social conditions that could have hindered the
delivery of such treatment. Where these disparities have been
addressed with effective programmes, improvements in once
worse outcomes for women have been turned around.
In fact, in 2009, Reeves et al8 found that sex disparity in
the delivery of thrombolysis existed; women had a 30% lower
odds of receiving recombinant tissue-type plasminogen activator treatment than men. In the meantime, the design IST 3
trial (Third International Stroke Trial) had removed an upper
age limit for enrolled patients, therein achieving an inclusion
rate of 52% for women.9 Furthermore, a recent report from the
Austrian Stroke Registry showed that correcting for age, no significant sex-related differences in quality of care were identified with comparable onset-to-door times, times to and rates of
neuroimaging, as well as emergency room door-to-needle times
and rates of intravenous thrombolysis (14.5% for both sexes).10
Yet, obstacles remain regarding the home door to emergency room door because women arrive to hospital more
often with private transport compared with men who more
than often arrive by ambulance. The German Stroke Registry
reported that intravenous thrombolysis and mechanical thrombectomy rates did not differ between males and females <80
years, but the rate of specialized stroke unit care was still lower
for women than in men.11 According to the same authors, this
lower admission could be explained by the Yentl syndrome.12
In fact, women are less likely to experience typical stroke
symptoms, including motor dysfunction, vertigo, and gait
dysfunction, but instead complain of pain or present with
reduction of consciousness,13 contributing to misdiagnosis,
nonadmission to an available stroke unit, and consequently a
worse outcome.
Regarding the results from the VISTA study, no systematic
research was performed on screening logs to understand how
many women could have been identified as possible candidates for the included randomized controlled trials or were
excluded for nonmedical issues. Finally, most randomized
controlled trials early dropouts were women.
T
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The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Stroke Unit, Santa Maria della Misericordia Hospital,
University of Perugia, Italy.
Correspondence to Valeria Caso, MD, PhD, Stroke Unit, Santa Maria
della Misericordia Hospital, University of Perugia, 06156 Perugia, Italy.
E-mail [email protected]
(Stroke. 2017;48:250-251.
DOI: 10.1161/STROKEAHA.116.015752.)
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.116.015752
250
Caso and Paciaroni Sex and Stroke 251
In conclusion, this study provides a well-defined snapshot of a certain subgroup of women who had the privilege of
receiving the best care in the best social environment.
However, most women worldwide lack one or even both
of these privileges. For instance, Kim et al14 have reported
that in countries with higher sex inequality (eg, lower rights
for women compared with men), a higher stroke mortality in
women has been observed. Lower access to job opportunities,
lack of domestic violence legislation, and inequalities in property ownership rights were associated with higher stroke mortality rates in women.14 This is in line with reports that stated
that women in low-income countries tend not to be admitted
to hospitals.15 This is probably because of the absence of a
universal healthcare system.16
The encouraging results from this analysis should be used
to formally implement stroke unit standards worldwide to
improve on outcomes in both men and women.
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Disclosures
None.
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KEY WORDS: Editorials ◼ sex ◼ sex disparities ◼ hypertension ◼ stroke care
◼ women
Sex Is Not a Risk Factor in Outcome When a Stroke Unit Treats the Patient
Valeria Caso and Maurizio Paciaroni
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Stroke. 2017;48:250-251; originally published online December 27, 2016;
doi: 10.1161/STROKEAHA.116.015752
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