Poor Outcome After First-Ever Stroke

Predictors for Death, Dependency, and Recurrent Stroke

Within the First Year
Peter Appelros, MD; Ingegerd Nydevik, MD, PhD; Matti Viitanen, MD, PhD
Background and PurposeThe purpose of this study was to define predictors of poor outcome after a first-ever stroke.
We studied risk factors and stroke severity at baseline in relationship to death, dependency, and stroke recurrence within
a year after the event.
MethodsThe study included a community-based cohort of first-ever stroke patients. Subarachnoid hemorrhage was not
included. All patients (n377) were subjected to investigations regarding risk factors. Stroke severity was evaluated
with the National Institutes of Health Stroke Scale, and dependency was defined according to the modified Rankin Scale.
Multivariate regression models were used to analyze predictors of survival, dependency, and stroke recurrence. The
following independent variables were used: age, sex, cohabitation status, cigarette smoking, dementia, hypertension,
ischemic heart disease, heart failure, atrial fibrillation, diabetes mellitus, transitory ischemic attack, peripheral
atherosclerosis, and stroke severity.
ResultsThe 1-year mortality was 33%. After 1 year, 37% of the survivors were dependent; 9% of survivors had a
recurrent stroke within a year. Dementia, age, stroke severity, and atrial fibrillation were associated with death within
a year. Dependency was associated with age, stroke severity, and heart failure. Stroke recurrence was predicted by age
and dementia.
ConclusionsIn addition to age and stroke severity, heart diseases and dementia before the stroke seem to have an impact
on mortality and recurrence after 1 year. Finding and, when possible, treating these prestroke conditions may affect
stroke morbidity and mortality favorably. (Stroke. 2003;34:122-126.)
Key Words: atrial fibrillation cognitive disorders heart failure, congestive prognosis stroke

n the last decades, in Sweden, as well as in many other

Western countries, stroke seems to have become a less
severe disease.1 The reasons for this are not clear, but it has
been suggested that a reduction in the population level of
blood pressure, diminished smoking, reduced intake of saturated fats, and better stroke care in dedicated units may
contribute.1,2 One way of affecting stroke morbidity and
mortality might be to further reduce the impact of factors that
increase stroke severity. Several authors have studied prognostic factors for long-time survival after stroke,313 stroke
recurrence,3,11,14 17 and functional outcome or dependency.4,13,18 23 Although few of these studies used populationbased materials, it is well established that old age and severe
impairment after stroke predict poor outcome. Few studies
have considered the impact of prestroke dementia, which is
now recognized as a risk factor for stroke.24,25 Dementia after
stroke is also known to have a negative impact on long-term
survival.26 We have previously shown that heart failure, atrial
fibrillation, and dementia are associated with more severe
strokes.27 The purpose of this article is to demonstrate the

impact of prestroke risk factors on the outcome of patients

who survived the acute phase of a stroke. We designed the
present study to compare 3 different domains of poor stroke
outcome, with special attention given to whether risk factors
other than age and stroke severity play a role.

Subjects and Methods

All cases of first-ever stroke were registered in rebro, Sweden,
during a 12-month period, from February 1, 1999, through January
31, 2000. The study population was 123 503. The World Health
Organization (WHO) definition of stroke was used.28 Cases were
found inside and outside the hospital. Multiple overlapping sources
and hot pursuit techniques were used in the process of case
ascertainment to fulfill the requirements of an ideal stroke incidence study.29 Patients with subarachnoid hemorrhage (n11) were
not included in the present study because of their different etiologies
and prognoses. Case ascertainment and the definition of stroke types
have been discussed in detail.30
A year after the stroke event, each patient was offered a free
follow-up consultation. Optional to the patient, the investigator
either saw the patient at the consulting room or visited the patient at

Received May 29, 2002; final revision received July 10, 2002; accepted August 16, 2002.
From the Departments of Neurology and Geriatrics, rebro University Hospital, rebro (P.A.), and the Department of Neurotec, Division of Geriatric
Medicine, Karolinska Institutet, Stockholm (P.A., I.N., M.V.), Sweden.
Correspondence to Dr Peter Appelros, Department of Neurology, rebro University Hospital, SE-701 85 rebro, Sweden. E-mail
peter.appelros@orebroll.se
2003 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

DOI: 10.1161/01.STR.0000047852.05842.3C

122
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Appelros et al
a house call. A single doctor (P.A.) evaluated 99% of the patients at
baseline and all patients at 1 year.
Stroke severity at baseline was assessed with the National Institutes of Health Stroke Scale (NIHSS).31 The assessment was performed within 24 to 48 hours after the event, except if a patients
general health was rapidly declining; in this case, the assessment was
performed within the first 24 hours. At the follow-up after 1 year,
dependency was assessed with the modified Rankin Scale (MRS).32
Functionally dependent was defined as an MRS score of 3, 4, or 5.33
The MONICA criterion for stroke recurrence34 was adapted: every
stroke event must have its apparent onset . . . more than 28 days from
any preceding stroke event. At the follow-up, the incidence of new
stroke events was verified in 1 of 3 ways. First, some stroke events
could be verified directly by the study doctor at the time of the new
stroke. Second, clear documentation in medical records of new focal
signs that had lasted 24 hours was accepted. Third, some patients
did not seek medical help when they had their second stroke but told
the study doctor and showed signs of it at the 1-year follow-up visit.
If a patient died within the year of follow-up, the cause of death was
researched in hospital or primary care medical records.
Strokes were divided into the following main types according to
the WHO criteria: brain infarction (BI), intracerebral hemorrhage
(ICH), and stroke of undetermined pathological type (UND). Risk
factors were evaluated at the time of stroke diagnosis. A structured
interview was done to map the relevant medical history of each
patient. When appropriate, the next of kin was interviewed. Previous
hospital medical records and, when relevant, primary care records
were reviewed. Assessment of prestroke dementia was based on
interviews with the patient and a knowledgeable informant. We
required the presence of memory impairment and deficits in at least
1 other cognitive ability. The presence of prestroke dementia was
established if these disabilities were severe enough to interfere with
everyday activities for at least 6 months or if there had been a
confirmed diagnosis of dementia according to medical records.
First-hand information was gained from a relative in 75% of patients.
This relative was most often the patients spouse, son, or daughter.
The diagnosis of dementia was based entirely on clinical grounds,
and both etiological main groups of dementiavascular and primary
degenerativewere included. For a comprehensive definition of risk
factors, we refer to our previous article.27 Population statistics were
used to ascertain whether a patient was still alive 1 year after the
stroke event.

Poor Outcome After First-Ever Stroke

TABLE 1.

123

Baseline Characteristics of the Study Population

No. of subjects

377

Age, average (range)

77 (33100)

Male sex, n (%)

169 (45)

Main types of stroke, BI/ICH/UND, n

274/44/59

Living alone, % (95% CI)

53 (4758)

Arterial hypertension, % (95% CI)

36 (3141)

Ischemic heart disease, % (95% CI)

30 (2535)

Whereof myocardial infarction

17 (1421)

Heart failure, % (95% CI)

14 (1017)

Atrial fibrillation, % (95% CI)

24 (2029)

Diabetes mellitus, % (95% CI)

18 (1423)

TIA, % (95% CI)

15 (1119)

Cigarette smoking, % (95% CI)

22 (1827)

Peripheral atherosclerosis, %
Prestroke dementia, % (95% CI)

4
12 (916)

Human Ethics Committee of the rebro County Council and the

local Data Inspection Board approved the study.

Results
Three hundred seventy-seven patients were found to have had
a first-ever stroke in rebro during the study period. Nineteen
were included retrospectively when the hospital discharge
records and death certificates were scrutinized. Two hundred
nine patients (55%) were female, and 168 were male. The
overall 28-day case fatality was 18.3% (95% CI, 14.7 to
22.5). The baseline characteristics of the study population are
given in Table 1. A CT of the brain was performed at baseline
in 84% of the patients. At the 1-year follow-up, 6 patients
denied consent to take part in the consultation visit but agreed
to answer questions in a telephone interview.

One-Year Mortality
Statistical Analysis
The Kaplan-Meier method was used to estimate the probability of
survival 1 year after the stroke event. Assuming binomial distribution, CIs for proportions were calculated with STATA, version 7.0.
Coxs regression and multiple logistic regression were used to
calculate which factors contributed to each outcome. We used SPSS,
version 11.0.
The regression analyses were performed as follows. All variables
except age and stroke severity were dichotomized. The 13 explanatory variables were first tested 1 by 1 against the dependent variable
for the presence of a significant association (P0.05). Variables for
which no significant association was found were removed from the
model. Thereafter, the remaining variables were cross tabulated to
assess for multicollinearity. In no cases were 2 variables correlated at
0.25 with each other, which was acceptable for the subsequent
analysis. The regression analysis was then performed. Finally, the
logistic regression models were examined for goodness of fit.
Deviance values were calculated to analyze how well the model fit
each case. The relative influence of individual observations was
analyzed by Cooks influence statistic. In all cases, it was concluded
that the model fit was adequate, and experimental removal of outliers
did not violate the model.

Ethics
Before entering the study, patients were asked orally for consent and
received written information. When a patients ability to communicate was restricted, consent was obtained from the next of kin. The

After 1 year, 124 patients had died. The overall 1-year

probability of death was 0.33 (95% CI, 0.28 to 0.38). The
survival probability for different stroke subtypes was as
follows: ICH, 0.36 (95% CI, 0.22 to 0.52); nonlacunar type of
BI, 0.29 (95% CI, 0.23 to 0.36); lacunar type of BI, 0.06 (95%
CI, 0.02 to 0.14); and UND, 0.78 (95% CI, 0.65 to 0.88). No
significant differences were seen between men and women.
Ninety-seven deaths (78%) were stroke related. Other causes
of death were heart disease (n9), malignant tumor (n7),
infection (n6), and other disease (n5).

Functional Outcome
At baseline, the median NIHSS score for all 377 patients was
6 (interquartile range, 3 to 12). The mean value was 9.2,
which indicates a positive skewness. For survivors, the
median score was 1.0 after 1 year (interquartile range, 0 to 3;
mean value, 2.2). No patient with a baseline NIHSS score of
30 survived the first year. These patients often had lowered
consciousness at the time of admission.
The frequency of different MRS scores at 1 year was as
follows: 42 (16%) scored 0, 58 (23%) scored 1, 60 (24%)
scored 2, 40 (16%) scored 3, 25 (10%) scored 4, and 28
(11%) scored 5.

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January 2003

TABLE 2. Hazard Ratios and Odds Ratios for Death, Dependency, and Stroke Recurrence Within 1 Year After First-Ever Stroke
According to Different Prestroke Risk Factors and Stroke Severity (95% CIs)
Hazard Ratios for Death

Odds Ratios for Dependency

Hazard Ratios for Stroke Recurrence

Risk Factor

Univariate Model

Multivariate Model

Univariate Model

Multivariate Model

Univariate Model

Multivariate Model

Age (per year)

1.07 (1.041.09)

1.05 (1.021.07)

1.07 (1.041.10)

1.08 (1.051.12)

1.12 (1.061.18)

1.11 (1.051.18)

Male gender

0.7 (0.50.9)

1.1 (0.71.8)

0.5 (0.21.0)

Living alone

1.5 (1.11.2)

1.2 (0.72.0)

1.2 (0.62.6)

Cigarette smoking

0.5 (0.30.9)

Prestroke dementia

4.0 (2.66.1)

1.9 (1.23.1)

0.6 (0.31.1)

0.3 (0.11.1)

2.1 (0.76.4)

5.1 (2.212.2)

Hypertension

0.8 (0.51.2)

0.7 (0.41.2)

0.9 (0.42.1)

Ischemic heart disease

1.2 (0.81.8)

1.6 (0.92.8)

2.5 (1.25.3)

Heart failure

2.2 (1.43.5)

Atrial fibrillation

2.7 (1.83.9)

3.2 (1.37.7)
2.4 (1.63.6)

3.0 (1.18.0)

1.6 (0.83.1)

1.5 (0.54.4)
2.1 (1.04.8)

Diabetes mellitus

1.0 (0.61.7)

1.6 (0.83.1)

0.4 (0.11.6)

TIA

1.1 (0.71.9)

1.4 (0.72.8)

1.0 (0.43.0)

Peripheral atherosclerosis
Stroke severity (per NIHSS unit)

1.3 (0.53.2)
1.15 (1.121.17)

3.0 (0.712.7)
1.15 (1.121.17)

Stroke Recurrence

1.26 (1.161.37)

3.0 (1.27.2)

2.5 (0.610.5)
1.33 (1.211.46)

1.06 (0.991.12)

Of the 310 survivors, 27 had a new stroke within the year of

follow-up. The overall 1-year probability of recurrence was
0.09 (95% CI, 0.06 to 0.12). The probabilities for different
stroke subtypes were as follows: ICH, 0.09 (95% CI, 0.02 to
0.23); nonlacunar type of BI, 0.10 (95% CI, 0.05 to 0.14);
lacunar type of BI, 0.03 (95% CI, 0.003 to 0.09); and UND,
0.29 (95% CI, 0.11 to 0.46). No significant differences were
seen between men and women. Half of the patients (n13)
did not seek medical help for their recurrent stroke, which
was recorded in the follow-up examination.

severity was dichotomized into mild stroke (NIHSS score

6) and severe stroke (NIHSS score 6). Obviously, this
changed the numerical values of the hazard ratios, but it did
not change which predictors were significant.
Coxs regression was also performed on different stroke
subtypes. Stroke severity, atrial fibrillation, and dementia
were significant in patients with both BI and ICH, whereas
age and heart failure were significant only in patients with BI.
Although differences between sexes were small, the impact of
age seemed somewhat larger on women, whereas atrial
fibrillation and dementia had a larger impact on men.

Risk of Death

Risk of Dependency

To evaluate which risk factors were independent predictors of

death within 1 year, Coxs proportional-hazards regression
analysis was used. The following explanatory variables were
included: (1) age, (2) sex, (3) living alone, (4) cigarette
smoking, (5) dementia, (6) hypertension, (7) ischemic heart
disease, (8) heart failure, (9) atrial fibrillation, (10) diabetes
mellitus, (11) previous transitory ischemic attack (TIA), (12)
peripheral atherosclerosis, and (13) stroke severity as measured with the NIHSS. Because of obvious covariation
between dementia and items 1b and 1c in the NIHSS
(questions and commands), these items were excluded from
this calculation.
The results of both the univariate analysis and the final
Coxs model (with 95% CIs and probability values) are
shown in Table 2. Hypertension, diabetes, ischemic heart
disease, and TIA variables were removed from the model
because of a lack of significant association. The following
variables were identified as the best predictors of death within
1 year: stroke severity, age, atrial fibrillation, and dementia.
Because of the heavy impact of stroke severity on mortality,
the model was also tried without stroke severity as an
explanatory variable. Then, heart failure, in addition to age,
atrial fibrillation, and dementia, was significant.
To further validate the model, age was divided into 4
categories (72, 72 to 77, 78 to 84, 84 years), and stroke

Logistic regression was used to determine the risk of dependency, defined as an MRS score 3, 1 year after a first-ever
stroke in 253 survivors. The explanatory variables listed
above were used. The results of both the univariate and the
multivariate analysis (with 95% CIs and probability values)
are shown in Table 2. Sex, hypertension, diabetes, ischemic
heart disease, TIA, and peripheral atherosclerosis were not
included in the multivariate model because of a lack of
significant association in the univariate model. The following
combination was identified as the best predictor of dependency after 1 year: stroke severity, age, heart failure, and
dementia.
In a logistic regression model performed for BI only,
diabetes mellitus, in addition to age and stroke severity, was
a significant predictor of dependency. When logistic regression was performed on the sexes separately, heart failure was
a significant predictor only in men, whereas age and stroke
severity were significant in both sexes.

Risk of Having a Recurrent Stroke

Coxs regression was used to evaluate which risk factors
could predict a recurrent stroke within a year from the first
stroke. The results are shown in Table 2. In the first step, all
variables except age, ischemic heart disease, and dementia
were removed because of a lack of significant association.

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Appelros et al
Age and dementia were identified as the best predictors of
recurrence.

Discussion
This community-based stroke study has shown that prestroke
dementia has an impact on outcome 1 year after stroke in
terms of mortality and recurrence. Furthermore, atrial fibrillation affects mortality, and heart failure is associated with
dependency after 1 year. Although our study is small compared with some longitudinal or multicenter studies, it has the
advantage of a complete case ascertainment, including even
cases managed outside the hospital, and a single investigator
who evaluated patients at both baseline and the 1-year
follow-up.
We have previously shown that prestroke dementia is a risk
factor for initial stroke severity and for 28-day case fatality.27
Others have shown that dementia after stroke increases the
risk of long-term stroke recurrence35 and shortens long-time
survival26 and that patients with cognitive impairment have
an increased risk of a first stroke.24,25 From the present study,
it is also evident that prestroke dementia is a risk factor for
death and stroke recurrence within 1 year. To the best of our
knowledge, this has not been shown before. The common
denominator between stroke and dementia may be apolipoprotein E 4, which is linked to both sporadic and lateonset Alzheimers disease,36 as well as dementia with
stroke.37 Patients expressing this apolipoprotein may be more
vulnerable to a vascular insult.38 This has been discussed in
more detail elsewhere.27 Because patients with dementia are
at an elevated risk of having a first stroke,24,25 they may well
be susceptible to a second stroke. However, it was not
possible to show that prestroke dementia had any influence
on dependency, although there was a tendency in that
direction.
Atrial fibrillation is perhaps the most well-recognized
cardiac risk factor. Atrial fibrillation increases stroke severity
and early mortality,27,39 as well as late mortality, as this and
other studies9 13 have shown. Atrial fibrillation is also associated with increased risk for a second ischemic stroke.16 The
latter was not shown in the present study, which may be
explained by the fact that 38% of the patients were on
warfarin after the stroke compared with only 7% before.
Also, the number of patients with recurrent stroke in this
study was small, which negatively affects precision.
The negative impact of heart failure on late mortality3,6,10 12 is well documented. Prestroke heart failure is
associated with more severe strokes,27 but the impact of heart
failure on 1-year mortality in the present study was significant only in univariate analysis and when stroke severity was
excluded from the multivariate analysis. The reason that heart
failure is associated with more severe strokes remains unclear, although it may predispose to cardiac embolism, which
gives rise to larger infarcts.40 Recently, it has been shown that
the administration of an angiotensin-converting enzyme inhibitor (ramipril) to patients at high risk of cardiovascular
events reduces the relative risk of stroke by 32%.41 There are
also proposals for 2 studies comparing warfarin and antiplatelet agents in patients with low ejection fraction.40 The
relationship between heart failure and stroke is certainly

Poor Outcome After First-Ever Stroke

125

interesting because it may open new possibilities for prophylactic treatment. A more aggressive attitude toward investigation and treatment of heart diseases may already have had
a part in lowering stroke mortality and morbidity in Western
countries. Ryglewicz and coworkers42 found that ischemic
strokes were more severe in Poland than in the United States.
They also found that cardiac diseases (coronary disease,
myocardial infarction, atrial fibrillation, and heart failure)
were more frequent in Poland than in the United States, while
the prevalence of hypertension, smoking, and diabetes mellitus was similar in the both countries.
Within a community-based study design, we have confirmed that age and stroke severity are risk factors for
mortality and dependency within the first year after a firstever stroke. We have also shown that ischemic heart disease,
heart failure, and atrial fibrillation have adverse influence on
long-term prognosis in different ways. The adverse effect of
prestroke dementia on stroke severity and short-term survival27 continues to influence long-term survival. It seems that
effective treatment of heart diseases, especially atrial fibrillation and heart failure, before and after a stroke may improve
outcome. Further studies are needed to confirm the impact of
dementia on stroke outcome, and the causal connection
remains to be explored.

Acknowledgments
This study was supported by grants from the Research Funds of
rebro County Council. We thank Professor ke Seiger for commenting on the manuscript and Anders Magnusson, BSc, for statistical advice.

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Poor Outcome After First-Ever Stroke: Predictors for Death, Dependency, and Recurrent
Stroke Within the First Year
Peter Appelros, Ingegerd Nydevik and Matti Viitanen
Stroke. 2003;34:122-126; originally published online December 5, 2002;
doi: 10.1161/01.STR.0000047852.05842.3C
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2002 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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