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Neuroepidemiology 2010;34:9096
DOI: 10.1159/000264826
Stanley Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,
Stroke Center, Department of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center,
Tel Hashomer, c School of Public Health, University of Haifa, Haifa, and d Neurology Department and Stroke Unit,
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
b
Key Words
Ischemic stroke Mortality rate, ischemic stroke Diabetes
Chronic heart failure Dementia Peripheral artery disease
Predictor
Abstract
Background: Despite declining age-adjusted stroke mortality rates, the disease remains the third most common cause
of death in Israel. Based on a national survey, we examined
mortality rates during the first 3 years after a first-ever acute
ischemic stroke (IS) and the major predictors of short-term
(1 month) and long-term (3 years) mortality. Methods: In the
National Acute Stroke Israeli Survey (NASIS 2004), data were
collected on all hospitalized stroke patients in Israel during
a 2-month period. Mortality rates for first-ever IS were assessed at 1 month and 3 years and predictors of death were
evaluated using the Cox proportional hazard model. Results: A total of 1,079 first-ever IS patients were included.
Survival data were complete for over 99% of patients. Cumulative mortality rates were 9.9% at 1 month and 31.1% at 3
years. Of the survivors at 1 month, 23.5% did not survive for
3 years. At 1 month, the hazard ratio (HR) for death significantly increased with stroke severity. One-month mortality
Introduction
Stroke is the third most common cause of death in European countries, accounting for high mortality in both
the short- and long-term. Reports from the European
Registries of Stroke Collaboration show that 1-month
mortality after stroke ranges from 13 to 27% [1]. The impact of stroke on mortality is evident several years after
the event: the risk of mortality for 1-year survivors is approximately 10% for each of the following 4 years, twice
as high as expected for the general population of the same
age and sex [2]. Age [3] and severity of stroke [3, 4] have
been reported to be the two major predictors of mortality
at 30 days. Age [35], previous cardiac disease [6], cardioembolic stroke [3], and diabetes [7] have been identified
as predictors of long-term mortality. Age-adjusted mortality rates after stroke have declined considerably during
the last decades in Israel. However, mortality trends show
a greater decline for Jews than for Arabs, a finding probably related to differences in risk factor distribution [8].
Identifying predictors of death after acute stroke is important for the development of secondary prevention
strategies and setting targets in the management of acute
stroke. Based on data from the first National Acute Stroke
Israeli Survey (NASIS 2004) [9], we present the rates of
mortality after first-ever acute ischemic stroke (IS) during the first 3 years after stroke and examine the major
potential predictors of short-term (1 month) versus longterm (3 years) mortality after IS.
clinical outcome was completed for all patients during hospitalization. Information on the etiology of IS was collected according
to the TOAST criteria. However, 42% of the ISs were classified as
undetermined mainly due to lack of in-hospital investigations.
The clinical OCSP criteria, which reflect the extent of the stroke,
were preferred for the classification of events in the present
study.
Mortality rates were prospectively assessed at 1 month and 3
years following stroke by means of matching patients files with
national mortality data. The study was approved by the ethical
committees of the participating hospitals.
Statistical Analysis
Cumulative mortality rates at the 1-month and 3-year followups were calculated for all hospitalized patients with first-ever IS.
Differences in baseline variables between survivors and non-survivors at 1 month and 3 years after the stroke were assessed with
the 2 test for proportions and the Students t test for continuous
variables. Determinants of death were evaluated using the Cox
proportional hazard model at 1 month and 3 years. The KaplanMeier survival curve at 1 month and 3 years and adjusted HR for
mortality at both periods are presented. At 3-year follow-up, data
analysis was conducted only for 1-month survivors. Analyses
were performed with the SAS 9.1 software.
Results
Neuroepidemiology 2010;34:9096
Methods
91
100
98
Survivors (%)
96
94
92
90
88
Survivors (%)
0 0.5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 18 19 20 22 23 24 25 27 28 29 30
Time from onset of IS (days)
100
98
96
94
92
90
88
86
84
82
80
78
76
0
8 10 12 14 16 18 20 22 24 26
Time from onset of IS (months)
28
30
32
34
36
Neuroepidemiology 2010;34:9096
Survivors
(n = 960, 90.1%)
Male gender
Hypertension
Dyslipidemia
Diabetes
Atrial fibrillation
Current smoking
Prior heart disease1
Peripheral artery disease
Malignancy
Family history of stroke (55 years)
Dementia
Decreased level of consciousness
Glucose on admission, mg/dl
Temperature on admission, C
WBC on admission, /mm3
SBP on admission, mm Hg
DBP on admission, mm Hg
517 (53.9)
648 (73.2)
431 (44.9)
375 (39.1)
152 (16.0)
193 (20.2)
306 (31.9)
64 (6.7)
64 (6.7)
29 (3.1)
63 (6.7)
91 (9.5)
151.5877.1
36.680.5
8,81883,134
161.7828.2
85.8814.7
Deceased
(n = 106, 9.9%)
45 (42.5)
73 (68.9)
37 (34.9)
44 (41.5)
40 (38.1)
9 (8.5)
42 (40.0)
8 (7.7)
15 (14.4)
1 (1.0)
13 (12.8)
61 (57.6)
178.6889.6
36.880.7
10,23684,162
157.4830.2
81.9818.3
p
0.03
0.35
0.05
0.63
<0.0001
0.004
0.11
0.71
0.005
0.23
0.03
<0.0001
0.004
0.002
0.0009
0.15
0.04
Unless otherwise indicated the values are the number of patients with percentages in
parentheses.
1
Prior acute myocardial infarction or angina pectoris or congestive heart failure or
valvular heart disease.
Survivors
(n = 734, 68.9%)
412 (56.1)
530 (72.6)
354 (48.2)
286 (39.0)
87 (12.0)
167 (22.9)
206 (28.1)
43 (5.9)
39 (5.4)
23 (3.2)
27 (3.7)
41 (5.6)
150.6876.7
36.680.5
8,63482,880
161.5827.0
85.9814.0
Deceased1
(n = 226, 23.5%)
105 (46.5)
168 (75.0)
77 (34.2)
89 (39.4)
65 (29.2)
26 (11.6)
100 (44.3)
21 (9.4)
25 (11.2)
6 (2.7)
36 (16.4)
50 (22.1)
154.5878.7
36.680.6
9,41583,789
162.2831.4
85.4816.7
p
0.01
0.5
0.0002
0.9
<0.0001
0.0002
<0.0001
0.07
0.003
0.7
<0.0001
<0.0001
0.5
0.4
0.005
0.7
0.7
Unless otherwise indicated the values are the number of patients with percentages in
parentheses.
1
Among 1-month survivors only.
2 Prior acute myocardial infarction or angina pectoris or congestive heart failure or
valvular heart disease.
Neuroepidemiology 2010;34:9096
93
Discussion
vascular territory
1-month mortality
(n = 106, 9.9%)
3-year mortality1
(n = 226, 23.5%)
12 (2.2)
24 (9.0)
15 (11.0)
23 (34.9)
31 (58.5)
66 (12.5)
70 (28.8)
50 (41.3)
26 (60.5)
13 (59.1)
36 (50.7)
107 (27.7)
33 (14.7)
39 (17.3)
8 (17.0)
Table 4. Cox survival model1 for determinants of 1-month and 3-year mortality in first-ever IS patients
1-month mortality
HR (95% CI)
3-year mortality2
HR (95% CI)
1.04 (1.021.07)
2.9 (1.75.1)
0.0002
0.0001
1.07 (1.061.09)
1.6 (1.02.4)
<0.0001
0.04
0.03
0.4
<0.0001
0.0002
0.008
0.03
1 (Ref.)
1.7 (1.22.5)
2.4 (1.63.6)
4.9 (2.88.8)
3.5 (1.58.1)
0.006
<0.0001
<0.0001
0.003
0.006
0.3
0.2
0.004
1 (Ref.)
1.9 (1.13.3)
1.2 (0.81.8)
0.7 (0.41.2)
1.7 (0.83.6)
1.5 (1.02.4)
1.6 (1.02.4)
1.6 (1.12.4)
1.7 (1.12.8)
1.7 (1.12.7)
0.04
0.4
0.2
0.2
0.05
0.04
0.01
0.03
0.02
1 (Ref.)
2.4 (1.15.0)
1.5 (0.63.7)
6.0 (2.514.5)
6.1 (2.315.8)
1.5 (1.12.1)
1.003 (1.0011.006)
1 (Ref.)
4.9 (1.615.2)
1.8 (0.65.4)
2.3 (0.77.3)
6.4 (1.822.2)
Age (year), gender, hypertension, dyslipidemia, diabetes, atrial fibrillation, current smoking, prior acute
myocardial infarction, angina pectoris, congestive heart failure, valvular heart disease, peripheral artery disease, malignancy, family history of stroke (55 years), dementia prior to stroke, decreased level of consciousness,
glucose on admission (mg/dl), temperature on admission ( C), WBC on admission (per mm3), SBP on admission (mm Hg), DBP on admission (mm Hg), severity of stroke on admission (NIHSS) and arterial territory
(OCSP classification) were included in the model, only significant variables are presented.
2 Among 1-month survivors only.
94
Neuroepidemiology 2010;34:9096
reports [26, 27]. The severity of stroke, a well-known predictor of short- and long-term mortality [24, 13], was an
important determinant of death in our study. A history
of previous cardiac disease has also been reported to increase the risk of mortality after stroke [24, 27], similar
to our present findings. Several studies have shown that
pre-stroke dementia is a risk factor for death during the
first year after the stroke [24, 28, 29]. We found that dementia was an independent risk factor for 3-year mortality among IS patients.
In our study, survivors at 3 years were, on average,
more than 10 years younger than the deceased. This considerable difference in age accounts most likely for most
of the long-term mortality. Additionally, risk factors like
malignancy and dementia are difficult to control. However, the age-adjusted proportions of diabetes and CHF
were considerably higher in the deceased compared with
survivors at 3 years; therefore improved control of these
factors can potentially prevent part of the long-term
deaths. Current international guidelines for management
of IS recommend optimal management of vascular risk
factors as part of the secondary prevention treatment
[30]. Unfortunately it is not clear to which extent these
guidelines are implemented.
Neuroepidemiology 2010;34:9096
Acknowledgment
We thank Ms. Rita Dichtiar, BSc, for her help with the statistical analyses.
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