Journal of the Neurological Sciences 335 (2013) 164–168

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Journal of the Neurological Sciences

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Effects of smoking on outcomes after acute atherothrombotic stroke in

Japanese men
Naoko Kumagai a,b,⁎, Yoshiyasu Okuhara a, Tatsuo Iiyama b, Yasunori Fujimoto c, Hidehiro Takekawa d,
Hideki Origasa e, Yu Kawanishi c, Takenori Yamaguchi f
a
Center of Medical Information Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan
b
Integrated Center for Advanced Medical Technologies, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan
c
Department of Neurosurgery, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan
d
Department of Neurology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan
e
Division of Biostatistics and Clinical Epidemiology, University of Toyama, Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan
f
National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Background: The effects of smoking on clinical outcomes following acute stroke remain controversial.
Received 16 June 2013 Methods: We evaluated the influence of smoking on 90-day outcomes after acute atherothrombotic stroke in 292
Received in revised form 27 August 2013 Japanese men extracted from the database of the Edaravone and Argatroban Stroke Therapy for Acute Ischemic
Accepted 16 September 2013 Stroke randomized parallel-group trial that tested the safety and efficacy of edaravone and argatroban therapy
Available online 25 September 2013
in 814 patients in 2004–2008. Smokers were matched with non-smokers of the same age for identical age
distribution in the smoker and non-smoker groups. Poor 90-day outcomes (defined as death, Barthel index b 60,
Keywords:
Acute atherothrombotic stroke
or modified Rankin score N 3) were evaluated using a logistic regression model. Significant variables (P b 0.05)
Age disparity between smokers and in univariate analysis were further evaluated by multivariate logistic regression analysis using a forward-
non-smokers selection method.
Gender difference Results: Body temperature, age, National Institute of Health Stroke Scale score at admission, systolic blood pres-
Japanese men sure, and smoking status were selected in the final model. Smokers had significantly increased odds of poor 90-
Poor outcome day functional outcomes independent of other statistically significant predictor variables (adjusted odds ratio,
Prognostic factor 2.28; 95% confidence interval, 1.15–4.55; P = 0.019).
Smoking
Conclusions: In Japanese men, smoking leads to poor functional outcomes at 3 months after acute atherothrombotic
stroke.
© 2013 Elsevier B.V. All rights reserved.

1. Introduction and diabetes mellitus, have been demonstrated to be prognostic factors

Stroke is a common neurological disorder leading to late-life disabil-
ity. More than one-third of patients who experience a stroke return to
their home with some level of permanent disability [1]. The sustained
impact of stroke has a devastating impact not only on the individual
and their caregivers but also on the wider family, particularly children
[1]. It is critically important to improve stroke outcomes in order to re-
duce the individual and social burden of care. The degree of functional
recovery after acute stroke is influenced by many factors; thus far, cer-
tain factors, including the location of lesions, severity of the ischemic ep-
isode, age, and the presence of other disorders, such as hypertension
⁎ Corresponding author at: Integrated Center for Advanced Medical Technologies, Kochi
Medical School, Kochi University, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan.
Tel.: +81 88 880 2719; fax: +81 88 880 2543.
E-mail address: kumagain@kochi-u.ac.jp (N. Kumagai).
[2,3]. Although smoking is a well-established risk factor for all forms of
stroke [4–6], the prognostic influence of smoking—an individual behav-
ior and a modifiable factor—following acute ischemic stroke remains a
matter of debate [7–9]. The prevalence of tobacco use has remained
largely unchanged over the last quarter of a century [4]. Therefore, clar-
ifying the role of smoking as a prognostic factor after acute stroke is im-
portant not only for improving stroke outcomes but also for appropriate
promotion of quitting the smoking habit.
We considered that the conflicting results available for smoking sta-
tus and the prognosis for stroke are results of inadequate adjustment for
confounding factors. Fewer women are smokers as compared to men,
and age disparities have been noted in smoking and non-smoking
groups in available researches on smoking and its prognostic effects
[7–9]. Therefore, in the present study, we targeted the stroke subtype
and gender and included age-matched subjects in order to eliminate
confounding factors. This study aimed to clarify the role of the smoking
habit as a prognostic factor for 90-day functional outcomes following
acute atherothrombotic stroke.

0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jns.2013.09.023
 N. Kumagai et al. / Journal of the Neurological Sciences 335 (2013) 164–168 165

2. Patients and methods in Table 1. We analyzed whether smoking status was associated with
poor outcomes at 90 days following acute atherothrombotic stroke
2.1. Patients using this dataset.

Data from the Edaravone and Argatroban Stroke Therapy for Acute
Ischemic Stroke study (EAST) database were used for analysis. The
EAST study was a randomized parallel-group trial conducted between
August 2004 and May 2008 that tested the safety and efficacy of combi-
nation therapy with argatroban and edaravone in 814 patients with
acute noncardioembolic and nonlacunar stroke in an unblended fashion
in Japan (ClinicalTrials.gov identifier: NCT00153946) [10]. Edaravone is
a free radical scavenger and a neuroprotective agent and argatroban is a
selective thrombin inhibitor. The detailed study design is available at
ClinicalTrials.gov. The EAST study showed no significance differences
between combination therapy with argatroban and edaravone and
argatroban alone with respect to safety and efficacy. Although previous
reports have suggested that thrombolytic therapy may be more effec-
tive in smokers than in non-smokers and that current smoking does
not affect the outcome of tissue plasminogen activator (t-PA) therapy
after adjusting for age [11,12], none of the patients in our study received
t-PA therapy.
First, data for 486 Japanese male patients with atherothrombotic
stroke from the EAST database were extracted for this study since the
majority of smokers in the EAST study were men and few women re-
ported the smoking habit. Second, because the mean age of the smoking
group was considerably lower than that of the non-smoking group in
the extracted database, we matched the age distribution between the
smoking and non-smoking groups in order to minimize the confound-
ing factors related to age. For such matching, 1 patient from the smoking
group was paired with 1 patient of the same age in the non-smoking
2.2. Ethics statement
The EAST study protocol was approved by the ethical committees of
the participating institutions and all participants provided written in-
formed consent.
2.3. Baseline factors and outcome
Age, smoking status, previous history of infarction, previous history of
transient ischemic attack (TIA), ischemic heart disease, hypertension, di-
abetes, hyperlipidemia, atrial fibrillation, systolic blood pressure (SBP),
diastolic blood pressure (DBP), body temperature, administration time
from stroke onset, size of infarction, number of ischemic lesions, use of
statin, use of aspirin, randomized treatment of the EAST study (mono-
therapy with argatroban vs. combination therapy with argatroban and
edaravone), and the National Institutes of Health Stroke Scale (NIHSS)
score at admission were selected as baseline covariate predictors. The
variable of the NIHSS score was divided into 3 categories, i.e., 1–4,
5–15, or ≥16. All patients were treated within 24 h from stroke onset
and were examined with both computed tomography and magnetic res-
onance imaging at baseline.
Table 1
Characteristics of smokers vs. non-smokers.

group. If there were no patients of the same age in both the smoking Characteristic Non- Smoker P
and non-smoking groups, such non-matched patients were excluded smoker (n = 146) value
from this study. Consequently, 146 pairs of non-smokers and smokers, (n = 146)

i.e., a total of 292 patients, from the EAST database were included in n % n %
the present study, as shown in Fig. 1. Thus, we ensured that the age dis- Agea (years) ≤50 2 (1.4) 2 (1.4)
tribution in the smoker and non-smoker groups was identical, as shown 51–60 16 (11.0) 16 (11.0)
61–70 60 (41.1) 60 (40.1)
71–80 56 (38.4) 56 (38.4)
N80 12 (8.1) 12 (8.1)
Enrolled subjects Administration time from stroke Mean ± SD 11.5 ± 6.2 12.5 ± 6.6 0.18
(n = 814) onset (h)
Systolic blood pressure (mm Hg) Mean ± SD 161.6 ± 158.6 ± 0.28
25.3 23.6
Diastolic blood pressure (mm Hg) Mean ± SD 87.9 ± 16.2 84.0 ± 14.7 0.034
Body temperature (°C) Mean ± SD 36.4 ± 0.53 36.4 ± 0.50 0.46
Japanese patients with acute NIHSS score at admission Median 4 [2,7] 5 [3,8] 0.10
atherothrombotic stroke (n = 701) [25%,75%]
1–4 88 (60.3) 70 (47.9) 0.10
4–15 51 (34.9) 68 (46.6)
≥16 7 (4.8) 8 (5.5)
Ischemic heart disease Yes 22 (15.1) 10 (6.8) 0.025
Previous infarction: Yes 21 (14.4) 25 (17.1) 0.52
Male subjects (n = 486) Female subjects (n = 215) Previous TIA Yes 5 (3.4) 3 (2.1) 0.72
Hypertension Yes 94 (64.4) 89 (61.0) 0.55
Smokers Smokers
Diabetes Yes 53 (36.3) 42 (28.8) 0.17
(n = 254; 52.3%) (n = 28; 9.9%) Hyperlipidemia Yes 41 (28.1) 42 (28.8) 0.90
Atrial fibrillation Yes 7 (4.8) 3 (2.1) 0.20
Number of ischemic lesions None 22 (15.1) 15 (10.3) 0.16
Single 107 (73.3) 104 (71.2)
Multiple 17 (11.6) 27 (18.5)
One patient from the smoking group was Size of infarction None/ 55 (37.7) 33 (22.6) 0.005
paired with one patient of the same age from ≤15 mm
the non-smoking group N15 mm 91 (62.3) 113 (77.4)
Argatroban/argatroban and
edaravone
Argatroban and edaravone 73 (50.0) 81 (55.5) 0.35
Use of statin Yes 23 (15.8) 22 (15.1) 0.87
Non-smokers (n = 146) and smokers (n = 146) Use of aspirin Yes 111 (76.0) 117 (80.1) 0.40
Total = 292 (Outcome n = 54) For analysis of continuous variables, t-test or Wilcoxon's rank-sum test was used; chi-
square test or Fisher's exact test was used to analyze categorical variables.
TIA, transient ischemic attack; NIHSS, National Institutes of Health Stroke Scale.
a
Fig. 1. Patient flowchart. Age was used as the matching variable.
166 N. Kumagai et al. / Journal of the Neurological Sciences 335 (2013) 164–168

Table 2
Associations between a poor outcome and a baseline factor.

Baseline factor Good outcome Poor outcome OR (95% CI) P value

n (%) n = 238 n (%) n = 54

Smoking Smoker 111 (46.6) 35 (64.8) 2.11 (1.14–3.89) 0.017⁎

Age (1 year) 69.0 ± 7.58 71.6 ± 8.53 1.05 (1.01–1.09) 0.025⁎
Previous infarction Yes 34 (14.3) 12 (22.2) 1.71 (0.82–3.58) 0.16
Previous TIA Yes 7 (2.9) 1 (1.9) 0.62 (0.08–5.17) 0.66
Hypertension Yes 149 (62.6) 34 (63.0) 1.02 (0.55–1.87) 0.96
Diabetes Yes 73 (30.7) 22 (40.7) 1.55 (0.85–2.86) 0.16
Hyperlipidemia Yes 68 (28.6) 15 (27.8) 0.96 (0.50–1.86) 0.91
Ischemic heart disease Yes 30 (12.6) 2 (3.7) 0.27 (0.06–1.15) 0.077
Atrial fibrillation Yes 9 (3.8) 1 (1.9) 0.48 (0.06–3.87) 0.49
Body temperature (°C) Mean ± SD 36.4 ± 0.51 36.6 ± 0.50 3.21 (1.69–6.13) b0.001⁎
Systolic blood pressure (mm Hg) 158.3 ± 23.7 168.0 ± 26.6 1.02 (1.00–1.03) 0.009⁎
Diastolic blood pressure (mm Hg) 85.5 ± 15.5 87.8 ± 15.9 1.01 (0.99–1.03) 0.34
NIHSS score at admission b0.001⁎
1–4 145 (60.9) 13 (24.0) 1
5–15 85 (35.7) 34 (63.0) 4.46 (2.23–8.92) b0.001⁎
≥16 8 (3.4) 7 (13.0) 9.76 (3.05–31.2) b0.001⁎
Size of infarction N15 mm 158 (66.4) 46 (85.2) 2.91 (1.31–6.46) 0.009⁎
Number of ischemic lesions 0.22
None 34 (14.3) 3 (5.6) 1
Single 170 (71.4) 41 (75.9) 2.73 (0.80–9.34) 0.11
Multiple 34 (14.3) 10 (18.5) 3.33 (0.84–13.2) 0.086
Argatroban/argatroban and edaravone
Argatroban and edaravone 123 (51.7) 31 (57.4) 1.26 (0.69–2.29) 0.45
Administration time from stroke onset (h) 12.1 ± 6.43 11.6 ± 6.32 0.99 (0.94–1.03) 0.54
Use of statin Yes 38 (16.0) 7 (13.0) 0.78 (0.33–1.87) 0.58
Use of aspirin Yes 187 (78.6) 41 (75.9) 0.86 (0.43–1.73) 0.67

TIA, transient ischemic attack; NIHSS, National Institutes of Health Stroke Scale.
An association between each baseline variable and stroke outcome was evaluated using univariate logistic regression analysis and its odds ratio (OR) and 95% confidence interval (CI) were
estimated.
⁎ Indicates P b 0.05.

The outcome at 90 days after the onset of acute atherothrombotic 3. Results

stroke was evaluated as the study endpoint. The Barthel index (BI)
and the modified Rankin scale (mRS), which are the most common out-
come measures used in stroke research and focus on stroke-related dis-
ability and motor function recovery, were used in this study. We defined
poor outcome as the presence of any of the following: death, mRS N 3,
or BI b 60 on 90 days [9,13].
2.4. Statistical analysis
The characteristics between non-smokers and smokers were com-
pared using the chi-square test or Fisher's exact test for categorical var-
iables, and the two-sample t-test or Wilcoxon's rank-sum tests for
continuous variables.
The association between a baseline factor and outcome was investi-
gated by using univariate and multivariate logistic regression analyses.
A variable was considered potentially associated with the outcome
when the p value was less than 0.05 in univariate logistic analysis. Var-
iables that reached this significance threshold were further evaluated by
multivariate logistic regression analysis, using a forward-selection
method with a significance level of entry of 0.05. The interactions of fac-
tors were also evaluated through a forward-selection method. The
goodness of fit was evaluated using the Hosmer–Lemeshow test, and
predictive ability was confirmed by c-statistics based on receiver oper-
ating characteristic analysis. External validation was performed using
a cross-validation method. In the cross-validation analysis, 233 patients,
i.e., 80% of the total patients were randomly selected from the entire
dataset then, the c-statistics and odds ratio were estimated with the
multivariate logistic model using this selected dataset. This process was
repeated 1000 times. Therefore, 1000 c-statistic values and 1000 odds
ratio for smoking were generated. The averages, minimum, and maxi-
mum values have been shown in this study.
All statistical tests were two-tailed, and the level of statistical signif-
icance was set at 0.05. All analyses were performed using SAS statistical
software, version 9.1 (SAS Institute Inc., Cary, NC).
3.1. Characteristics of the entire EAST study dataset
The original EAST database of acute atherothrombotic stroke pa-
tients shows that the male subpopulation includes 52.3% smokers,
while the female subpopulation only includes 9.9% smokers (Fig. 1).
The mean age of the male non-smoking group was 72.0 years, while
that of the male smoking group was 65.8 years; further, the smoking
group also included extremely young male patients (P b 0.001).
3.2. Baseline characteristics between non-smokers and smokers
The smokers had a lower value of DBP, a lower frequency of ischemic
heart diseases, and larger infarction sizes (P b 0.05) at baseline (Table 1).
3.3. Association between baseline factors and poor outcome
As shown in Table 2, age (OR = 2.11, P = 0.017), SBP (OR = 1.02,
P = 0.009), body temperature (OR = 3.21, P b 0.001), NIHSS score at
the time of admission (score: 5–15 and ≥16; OR = 4.46, OR = 9.76,
respectively, P b 0.001), and size of infarction (OR = 2.91, P = 0.009)
were selected as candidate covariates, in addition to smoking status
(OR = 2.11, P = 0.017).
Multivariate logistic regression model with forward-selection includ-
ed smoking status (OR, 2.28; 95% CI, 1.15–4.55; P = 0.019), age (OR,
1.06; 95% CI, 1.01–1.11; P = 0.014), SBP (OR, 1.02; 95% CI, 1.00–1.03;
P = 0.0096), body temperature (OR, 3.27; 95% CI, 1.59–6.72; P =
0.001), and NIHSS score at admission (score: 5–15 and ≥16; OR, 4.05;
95% CI, 1.93–8.51; P b 0.001; and OR, 9.45; 95% CI, 2.64–33.8; P b 0.001,
respectively) as shown in Table 3. No interaction terms were selected.
The final model for c-statistic was 0.80, and the P value for the Hosmer–
Lemeshow goodness-of-fit test was 0.61. The model demonstrated ex-
cellent discrimination and acceptable calibration.
 N. Kumagai et al. / Journal of the Neurological Sciences 335 (2013) 164–168
Table 3
Associations between poor outcomes and smoking, with controlling confounding variables.
Risk factor Adjusted OR (95% CI) P value
Smoking
Smoker 2.28 (1.15–4.55) 0.019
Age (years) 1.06 (1.01–1.11) 0.014
Systolic arterial pressure 1.02 (1.00–1.03) 0.0096
Body temperature 3.27 (1.59–6.72) 0.0013
NIHSS score at admission
5–15 4.05(1.93–8.51) b0.001
≥16 9.45 (2.64–33.8) b0.001
NIHSS, National Institutes of Health Stroke Scale.
The model included smoking and candidate confounding variables, i.e., age, systolic
arterial pressure, body temperature, NIHSS score and size of infarction, with P b 0.05 in
univariate analysis. The forward selection approach in multivariate logistic regression
was performed; then, smoking age, systolic arterial pressure, body temperature, and
NIHSS were selected. The size of infarction was not selected; it was confirmed that there
were no interactions between any of the 2 variables when the selection criterion was set
as P b 0.05.
Hosmer–Lemeshow test (chi-square = 6.38, degree of freedom = 8, P = 0.61).
C-statistics = 0.80.
3.4. Validation
The final model, including the variables of smoking status, age, body
temperature, systolic body pressure, and NIHSS scores were used and
odds ratio and c-statistics were estimated in the model with the
resampled dataset. The distribution of 1000 different c-statistics ranged
from a minimum value to a maximum value of 0.75 to 0.85, with a mean
value of 0.80 for the resampling population, which was the same as the
c-statistic (0.80) derived from the entire dataset. The distribution of
1000 different ORs of smoking ranged from 1.27 to 5.04, with a mean
of 2.36 for the resampling population, which was significantly more
than 1.00.
4. Discussion
Our findings demonstrate that Japanese male smokers in the EAST
study experienced poorer outcomes than did non-smokers following
acute atherothrombotic stroke; smoking was thus indicated to be an
independent, poor prognostic factor for Japanese men after acute
atherothrombotic stroke. Two previous studies for this issue have
shown contradictory results, wherein one study suggested that current
or recent smokers with acute ischemic stroke experienced poorer func-
tional outcomes at 3 months as compared to non-smokers [8], whereas
the other observed that current smokers with acute ischemic stroke
experienced better long-term outcomes over a 6-month period than did
non-smokers [9]. These conflicting results have 3 potential explanations,
as clarified below.
First, although both results were obtained after adjusting the co-
variates by using multivariate regression analysis, there was an age
disparity between smokers and non-smokers, with smokers being
significantly younger than non-smokers. The age differences between
non-smokers and smokers in both studies were considerable; therefore,
the confounding factors could not be sufficiently adjusted in these
studies. Age difference is a critical problem that has also affected inves-
tigations examining the association between smoking status and prog-
nosis after myocardial infarction. Because younger people tend to have
lesser comorbidities and are more physically fit, the results of better
outcomes or decreased mortality rates after an acute myocardial infarc-
tion were considered to be due to the younger age of the smoking group
(as compared to that of the non-smoking group) rather than any
benefits from smoking [14]. We reviewed several papers concerning
smoking status and stroke and found that in these studies, the smoking
groups included significantly younger and a higher number of male
167
patients than did the non-smoking groups [5–9,11,12]. A large age
difference cannot be controlled by multivariate regression analysis and
can yield confusing results. Although the latter study used age-stratified
analyses, the number of outcomes was small and could not adequately
control the confounding factors.
Second, an increasing body of evidence has shown gender-specific
differences in the etiology of stroke as well as in stroke symptoms and
prognosis after ischemic stroke [15–18]. Some of these differences may
have important implications because of the gender-specific differences
in responses to nitric oxide, which is a component of cigarette smoke
[19,20]. Typically, fewer women report a smoking habit than men
[5–8,11,12]. Therefore, analyzing these factors together may cause fur-
ther bias while estimating the effects of smoking.
Third, although the prognostic effect of smoking status was differen-
tially related to the mechanism of stroke [21], previous studies have not
well accounted for the differences in ischemic stroke subtypes. Specifi-
cally, they did not perform stratified analysis by subtype, or if they did
so, the methods failed to adjust for other confounding factors.
These oversights together could have affected the contradictory re-
sults of these previous studies. All the atherothrombotic patients includ-
ed in the EAST study also demonstrated an age disparity related to the
smoking status along with few female smokers, similar to that in
other studies. Therefore, in the present study, we included only male pa-
tients with atherothrombotic stroke and matched the age distribution
for the smoker and non-smoker groups to be identical, as shown in
Table 1. Six factors, i.e., smoking status, age, SBP, body temperature,
NIHSS score at admission, and size of infarction were selected as poten-
tial candidate prognosis factors in univariate analysis. Subsequently, the
multivariable model revealed smoking status, age, SBP, body tempera-
ture, and NIHSS score at admission to be significant prognosis factors,
with no interaction terms among them. Only a single factor, i.e., size of
infarction, was excluded from the final model through the forward-
selection step, as shown in Table 3. The reason for exclusion of size of
infarction may be the lack of statistical power supporting this factor;
the size of infarction was weakly correlated with age and smoking status,
and such correlations are known to decrease statistical power [22,23].
Thus, smokers showed a significantly increased likelihood of poor
functional outcomes at 90 days in the final multivalent model (Table 3).
The final multivariate model demonstrated excellent discrimination
and acceptable calibration based on results of c-statistics and Hosmer–
Lemeshow test. Our cross-validation analysis also supported the reli-
ability of our results.
At baseline, the smokers had larger infarct sizes as compared to non-
smokers, as shown in Table 1. With respect to the infarct size, although
size of infarction was not included in the final multivariate model, pos-
sibly due to the lack of statistical power, this was significantly associated
with poor outcomes at 90 days in the univariate logistic model
(Table 2). The size of infarction has already been demonstrated to be
a prognostic factor [24–27]. In addition, nicotine has previously been
shown to increase the size of infarction in animal models [28,29]. Nicotine
may thus be directly or indirectly associated with factors causing larger
infarcts, thereby leading to poor functional outcomes in smokers.
A limitation of the present study is that this was a secondary analysis
of a previously completed randomized trial rather than a prospective
study specifically designed to address the present question. Therefore,
we were unable to collect detailed information on the number of ciga-
rettes smoked daily, the duration of smoking, or changes in the smoking
habit of the investigated patients at 90 days after stroke. We were also
unable to provide a continuous scale of infarct size. Moreover, associa-
tions between Japanese male smokers and low education level, consid-
ered to be related to low income, little physical activity, and irregular
breakfast habits, have been suggested [30]; while it is possible that
these factors are potentially related to outcomes, this information was
not collected in the present study. Further investigations are needed
to clarify the relationship between smoking status and clinical outcomes
following acute atherothrombotic stroke, including the association
168 N. Kumagai et al. / Journal of the Neurological Sciences 335 (2013) 164–168
between smoking and infarct size. However, it should be noted that all
the patients were examined with both computed tomography and mag-
netic resonance imaging (the infarct sizes in all patients were assessed).
Further, although certain clinical factors such as serum cholesterol
levels were not examined, clinically many important factors were in-
cluded in our analysis, and our model was proven to have a good fit by
c-statistics and the Hosmer–Lemeshow test. Moreover, our validation
testing supported the reliability of our results.
To the best of our knowledge, this is the first report to address the in-
fluence of smoking on functional outcomes after acute atherothrombotic
stroke by analyzing an age-balanced dataset that specified both gender
and the stroke subtype. Our findings indicate that smoking increases
the likelihood of poor functional outcomes among male Japanese patients
who experience acute atherothrombotic stroke.
Conflicts of interest
The authors declare that there are no conflicts of interest.
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