Predictors of Severe Stroke

Influence of Preexisting Dementia and Cardiac Disorders

Peter Appelros, MD; Ingegerd Nydevik, MD, PhD; Åke Seiger, MD, PhD; Andreas Terént, MD, PhD

Background and Purpose—There is little research into the impact of prestroke dementia on stroke severity and short-term
mortality. We included prestroke dementia, along with other risk factors, to determine independent predictors of stroke
severity and early death in a community-based stroke study.
Methods—All patients (n⫽377) with a first-ever stroke were evaluated in terms of risk factors. Registration took place over
a 12-month period. Stroke severity was evaluated with the National Institutes of Health Stroke Scale. Predictors of
severe stroke and early death were analyzed in logistic regression models. The following independent variables were
used: age, sex, living alone, arterial hypertension, ischemic heart disease, heart failure, atrial fibrillation, diabetes
mellitus, transient ischemic attack, cigarette smoking, peripheral atherosclerosis, and dementia.
Results—Risk factors for stroke were found in 82% of the patients. Heart failure, atrial fibrillation, and dementia were
associated with more severe strokes. Dementia, atrial fibrillation, heart failure, and living alone were associated with
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death within 28 days of the event.

Conclusions—These results raise the question of whether certain high-risk patients, ie, patients with atrial fibrillation, heart
failure, and dementia, can benefit from more aggressive primary and secondary stroke prevention measures. (Stroke.
2002;33:2357-2362.)
Key Words: atrial fibrillation 䡲 cognitive disorders 䡲 heart failure 䡲 prognosis 䡲 stroke

T he major risk factors for stroke are age,1 male sex,1

arterial hypertension,2 cigarette smoking,3 diabetes mel-
litus,4 atrial fibrillation (AF),5 and other cardiac disorders.6 In
addition, some of the risk factors, eg, AF7–9 and heart
failure,10 –12 are predictors of case fatality. In recent years, the
association between cognitive disorders and stroke has come
into focus. Currently, there is evidence that dementia is a risk
factor for stroke13,14 and that dementia after stroke has a
negative impact on long-term survival.15 There has, however,
been little research into the impact of prestroke dementia on
stroke severity and short-term mortality. We therefore in-
cluded prestroke dementia, along with other risk factors for
stroke, in a multivariate analysis to evaluate its impact on
stroke severity and early death. This was accomplished within
the frames of a community-based stroke study. All patients
with brain infarction (BI), intracerebral hemorrhage (ICH),
and undetermined pathological type (UND) were examined
for relevant medical history, and stroke severity was defined
for each patient.
Subjects and Methods
The study population included all inhabitants of the municipality of
Örebro, Sweden, during the 12-month study period, 123 503 as of
December 31, 1999 (48.4% men, 51.6% women). Details regarding
the case ascertainment have been described elsewhere.16 The study
was population based; ie, subjects were traced outside and inside the
hospital. World Health Organization diagnostic criteria were used.17
The data collection was prospective, and subjects were identified in
several overlapping ways by use of the “hot pursuit” technique; ie,
subjects were pursued as they occurred.
A single study doctor (geriatrician with 20 years of experience)
examined all suspected cases, whether detected by us directly or
reported to us by our clinical collaborators. A neurological exami-
nation was performed, and stroke severity was defined according to
the National Institutes of Health Stroke Scale (NIHSS).18 The
medical examination was performed 24 to 48 hours after the event,
except if a patient’s general health was rapidly declining, in which
case the examination had to be done within the first 24 hours. The
NIHSS score was estimated from information in patient records in 19
cases when patients were discovered retrospectively.19 A CT scan
was performed in 84% of the patients. Patients were divided into the
following main types of stroke: BI, ICH, UND, and subarachnoid
hemorrhage (SAH). For the purposes of this study, patients with a BI
were further classified according to the Oxford Community Stroke
Project20 into those with lacunar infarcts and those with other
infarcts. Patients with SAH were not included in the present study
because of the different origin.
The evaluation of risk factors was done at the time of stroke
diagnosis. A structured interview was performed by the main author
(P.A.) to map the relevant medical history of each patient. Next of
kin was interviewed when a patient was unconscious or disoriented.
This was necessary in 35% of the patients. Previous hospital medical
records and, when relevant, primary care records were reviewed.
First-hand information on cardiovascular diseases was gained from

Received February 11, 2002; final revision received May 22, 2002; accepted May 23, 2002.
From the Departments of Neurology and Geriatrics, Örebro University Hospital, Örebro (P.A.); Neurotec Department, Karolinska Institutet, Stockholm
(P.A., I.N., Å.S.); and Department of Medical Sciences, University of Uppsala, Uppsala (A.T.), Sweden.
Correspondence to Dr Peter Appelros, Department of Neurology, Örebro University Hospital, S-701 85 Örebro, Sweden. E-mail
peter.appelros@orebroll.se
© 2002 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000030318.99727.FA

2357
 2358 Stroke October 2002

TABLE 1. Medical History According to Stroke Subtypes

BI (n⫽274)

ICH All Lacunar Other UND All

(n⫽44) (n⫽274) (n⫽78) (n⫽196) (n⫽59) (n⫽377)
Average age (SD), y 73 75 72 77 85 77 (11)
Male sex, n (%) 25 (57) 125 (46) 38 (49) 87 (44) 19 (32) 169 (45)
Living alone, % (95% CI) 48 49 50 48 80 53 (47–58)
Arterial hypertension, % (95% CI) 32 38 40 37 26 36 (31–41)
Ischemic heart disease, % (95% CI) 25 32 18 37 24 30 (25–35)
With myocardial infarction 18 17 5 21 19 17 (14–21)
Heart failure, % (95% CI) 14 12 6 14 20 14 (10–17)
Atrial fibrillation, % (95% CI) 16 24 12 29 31 24 (20–29)
Diabetes mellitus, % (95% CI) 9 19 27 15 24 18 (14–23)
TIA, % (95% CI) 7 17 9 20 12 15 (11–19)
Cigarette smoking, % (95% CI) 21 25 37 19 7 22 (18–27)
Peripheral atherosclerosis, % 0 3 4 3 10 4
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Dementia, % (95% CI) 9 8 1 10 34 12 (9–16)

medical records in 75% of patients. The reverse was true regarding
cigarette smoking and dementia, which was not always documented
in medical records.
Arterial hypertension was diagnosed when its presence was
documented in medical records. Alternatively, it was diagnosed
when ⱖ2 readings of blood pressure were ⱖ160 mm Hg (systolic) or
ⱖ95 mm Hg (diastolic) before the onset of stroke. Ischemic heart
disease was diagnosed when there was a history of angina pectoris or
myocardial infarction. The diagnosis of heart failure was established
if this condition was documented in medical records and the patient
was still on medical treatment at the time of stroke. AF was
diagnosed either when there was a documented history of paroxys-
mal AF or if AF was present at the time of stroke. Diabetes mellitus
was diagnosed if the patient gave a history of diabetes that was
confirmed by their medical records or was taking insulin or an oral
hypoglycemic agent. Prestroke transient ischemic attack (TIA) was
diagnosed if it was documented in medical records or from the
patient’s own report that all symptoms relieved within 24 hours. A
patient was defined as a smoker if there had been a history of
cigarette smoking during the last 5 years. Peripheral atherosclerosis
was diagnosed when a patient had a history of calf pain induced by
exercise or if the patient had been subjected to positive angiography
or vascular surgery. 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 other
cognitive abilities according to the International Classification of
Diseases, 10th Revision.21 The presence of prestroke dementia was
established if these disabilities had been so severe as to interfere with
everyday activities for at least 6 months or if there had been a
confirmed diagnosis of dementia according to medical records. In
addition to medical risk factors, age, sex, and living alone were
recorded. Population statistics were used to ascertain whether a
patient was still alive 28 days after the stroke event.
Ethics
Before entering the study, patients were asked orally for consent.
They also received an information letter. If a patient’s ability to
communicate was restricted, consent from next of kin was obtained.
The Human Ethics Committee of the Örebro County Council and the
local Data Inspection Board approved the study.
Statistical Analysis
Assuming the binomial distribution, confidence intervals (CIs) for
proportions were calculated with the STATA software package,
version 7.0. Multiple logistic regression was calculated with the
SPSS package, version 11.0.
The logistic regression was performed as follows. All variables
except age were dichotomized. The outcome variable was dichoto-
mized to either mild stroke (NIHSS score ⬍6, n⫽185), or severe
stroke (NIHSS score ⱖ6, n⫽192). This level was chosen to divide
the cohort into equal halves. Age was categorized into 4 groups
(⬍72, 72 to 77, 78 to 84, and ⬎84 years) so that the categories were
of approximately uniform size. The 12 explanatory variables were
first tested 1 by 1 against the dependent variable for the presence of
significant association (P⬍0.05). Variables for which no significant
association was found were removed from the model. Thereafter, the
remaining variables were cross tabulated to assess for multicollinear-
ity. In no case were variables correlated at ⬎0.32, which was
acceptable for the subsequent analysis. The logistic regression
analysis (forward stepwise method) was then performed. Finally, the
model was 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 Cook’s influ-
ence statistic. In both cases, it was concluded that model fit was
adequate, and experimental removal of outliers did not violate the
model.
Results
Between February 1, 1999, and January 31, 2000, 377
patients were found to have had a first-ever-in-a-lifetime
stroke (non-SAH). Nineteen were included retrospectively
when hospital discharge records and death certificates were
scrutinized. Of the 377 patients, 208 were women, and 169
were men. The mean age for all patients was 76.6 years (for
women, 78.9 years; for men, 73.9 years). The distribution of
stroke types was as follows: BI, 73% (95% CI, 68 to 77);
ICH, 12% (95% CI, 9 to 15); and UND, 15% (95% CI, 12 to
20). No patients were lost during follow-up.
Medical History
A history of risk factors for stroke (arterial hypertension,
ischemic heart disease, heart failure, diabetes mellitus, TIA,
cigarette smoking, atherosclerosis of peripheral arteries, AF,
or dementia) was obtained in 82% of the patients. The
frequencies according to stroke subtypes are given in Table 1.
 Appelros et al Dementia and Stroke Severity 2359

TABLE 2. ORs for a Severe Stroke (NIHSS Score >6) and for 28-Day Case Fatality According to Different Prestroke
Risk Factors
OR for a Severe Stroke OR for 28-d Case Fatality

Univariate Multivariate Univariate Multivariate

Model Model Model Model
Risk Factor (95% CI) P (95% CI) P (95% CI) P (95% CI) P
Age (per class) 1.32 (1.1–1.6) ⬍0.01 0.16 1.60 (1.2–2.1) ⬍0.01 0.30
Male sex 0.75 (0.5–1.1) 0.17 0.60 (0.4–1.0) 0.07
Living alone 1.39 (0.9–2.1) 0.12 2.27 (1.3–4.0) ⬍0.01 1.94 (1.0–3.6) 0.04
Arterial hypertension 1.00 (0.7–1.6) 0.99 0.53 (0.3–1.0) 0.04 0.52 (0.3–1.0) 0.05
Ischemic heart disease 1.03 (0.7–1.6) 0.90 0.82 (0.5–1.5) 0.53
Heart failure 2.54 (1.4–4.7) ⬍0.01 2.25 (1.2–4.2) 0.01 2.63 (1.4–5.1) ⬍0.01 2.41 (1.2–5.0) 0.02
AF 2.07 (1.3–3.4) ⬍0.01 1.90 (1.2–3.1) 0.01 2.31 (1.3–4.0) ⬍0.01 2.43 (1.3–4.5) ⬍0.01
Diabetes mellitus 1.02 (0.6–1.7) 0.94 1.32 (0.7–2.6) 0.41
TIA 1.03 (0.6–1.8) 0.91 0.85 (0.4–1.8) 0.69
Cigarette smoking 0.59 (0.4–1.0) 0.05 0.42 (0.2–1.0) 0.04 0.16
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Peripheral atherosclerosis 1.54 (0.6–4.4) 0.41 1.66 (0.5–5.4) 0.40

Dementia 1.97 (1.1–3.7) 0.04 1.96 (1.0–3.7) 0.04 4.62 (2.4–9.0) ⬍0.01 4.29 (2.0–9.0) ⬍0.01

Only 6 of 90 patients (7%) with AF were on warfarin before
the event.
Stroke Severity
At the examination, 59% of the patients had no impairment of
consciousness, whereas 48% were conscious and oriented,
according to the NIHSS. Thirty-four percent of patients had
some degree of visual field disturbance, and 83% had some
degree of motor deficit. Ataxia was present in 12%, sensory
disturbance in 37%, aphasia in 31%, dysarthria in 42%, and
extinction or inattention in 14%. The median NIHSS score
was 6 (range, 0 to 38; interquartile range, 3 to 12), and the
mean value was 9.2, which indicates a skewed distribution.
For individual subtypes of stroke, the median scores were as
follows: ICH, 9 (range, 1 to 38; interquartile range, 4 to 15.5);
nonlacunar type of BI, 6 (range, 0 to 38; interquartile range,
2 to 11); lacunar type of BI, 3 (range, 1 to 14; interquartile
range, 3 to 5); and UND, 13.5 (range, 2 to 38; interquartile
range, 7 to 25).
Risk Factors for a Severe Stroke and 28-Day
Case Fatality
To evaluate whether any risk factors were independent
predictors of stroke severity or 28-day case fatality, we
analyzed the data in 2 logistic regression models. The results
of the NIHSS assessment and the 28-day case fatality were
used as dependent variables. The following explanatory
variables were used: (1) age, (2) sex, (3) living alone, (4)
arterial hypertension, (5) ischemic heart disease, (6) heart
failure, (7) AF, (8) diabetes mellitus, (9) previous TIA, (10)
cigarette smoking, (11) peripheral atherosclerosis, and (12)
dementia. Because of obvious covariation between dementia
and the items 1b and 1c in the NIHSS (Questions and
Commands), these items were excluded from analysis.
Eleven patients (3%) were not included in the logistic
regression because of missing data regarding risk factors.
These 11 patients did not differ from the others with respect
to age and sex but more often had a UND stroke (55%), more
often were demented (45%), and had a 28-day case fatality
of 90%.
The results of analyses (with 95% CIs and probability
values) are shown in Table 2. Age, heart failure, AF, and
dementia were included in the multivariate analysis for stroke
severity because of significant association in the univariate
analysis. The following combination was identified as the
best predictor variables for severe stroke: heart failure, AF,
and dementia. The model was also tested with other NIHSS
cutoff levels for the severe stroke criterion. When this level
was set to 10 (ⱕ10, n⫽286; ⬎10, n⫽91), there was only 1
significant explanatory variable left: AF. When the NIHSS
cutoff level was set to 15 (ⱕ15, n⫽315; ⬎15, n⫽62), the
only significant explanatory variable was dementia. To fur-
ther explore the association between the age variable and
dementia, we tested the model with the age variable dichot-
omized. The cutoff value was set to 84 years, which was the
mean age of patients with dementia. Dementia then still
remained a significant independent variable.
In the logistic regression model for 28-day case fatality, the
variables sex, ischemic heart disease, diabetes mellitus, TIA,
and peripheral atherosclerosis were removed because of lack
of significant association in the univariate analysis. The
following variables were identified as the best predictors of
death within 28 days: dementia, AF, heart failure, living
alone, and arterial hypertension.
We also performed an analysis in which stroke severity
(dichotomized as above, NIHSS ⬍6 or ⱖ6) was introduced as
an independent variable for case fatality, in addition to the
above-mentioned variables. Logistic regression then showed
only 2 variables that were independent predictors of case
fatality: stroke severity (odds ratio [OR], 24.41; 95% CI, 8.5
to 89.7) and dementia (OR, 2.35; 95% CI, 1.1 to 5.0). Heart
failure, AF, and living alone were nonsignificant.
 2360 Stroke October 2002
Discussion
This study has shown that certain prestroke risk factors have
an impact on neurological symptoms and case fatality in the
acute phase. These risk factors are dementia, AF, heart
failure, and living alone. The most challenging of them is
prestroke dementia.
Stroke is strongly associated with dementia.14 The identi-
fication of poststroke dementia may be affected by brain
damage after the stroke event itself; therefore, its presence
has limited value as a risk factor for stroke. We evaluated
prestroke dementia in a manner similar to that of Pohjasvaara
and coworkers.22 They found prestroke dementia in 9.2% of
their study group, which comprised patients 55 to 85 years of
age. Hénon and coworkers23 and Barba and coworkers24 used
a questionnaire. They found that 16% and 15%, respectively,
of their patients were demented before stroke. These studies
were hospital based and included recurrent stroke, which may
limit comparison with our study.25 The higher prevalence of
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prestroke dementia found in the latter 2 studies may also
reflect a higher sensitivity of a questionnaire for milder
dementia.
It has previously been reported that clinically stroke-free
individuals with severe cognitive impairment are at an ele-
vated risk of first stroke.13,14 Dementia after stroke also has a
negative impact on long-term survival,15 and stroke patients
with dementia are at an elevated risk of long-term stroke
recurrence compared with nondemented stroke patients.26 To
the best of our knowledge, it has not been shown previously
in multivariate analysis that prestroke dementia is a risk
factor for stroke severity and early death. However, Hénon
and coworkers23 found in bivariate analysis that in-hospital
mortality, functional outcome at discharge, and 6-month
mortality were worse in patients with prestroke dementia.
They failed, however, to show an effect on short-term
outcome in multivariate analysis. The discrepancy between
their study and ours in this respect may be explained by 3
factors. First, their study was hospital based and included
recurrent and first-ever stroke. Second, they used a question-
naire that may have been more sensitive to milder forms of
dementia. Third, they excluded more patients because of lack
of an informant. Taken together, these 3 factors may imply
that our patients had more extensive prestroke cognitive
impairment.
A question arises as to how stroke and dementia are
associated. One suggestion, although purely conjectural, may
be that apolipoprotein E plays a role. The isoform apolipopro-
tein E ⑀4 (apoE4) is strongly linked to both sporadic and
late-onset Alzheimer’s disease,27 as well as to dementia with
stroke.28 Recently, it has been shown that in terms of a
neurological severity score, transgenic mice expressing hu-
man apoE4 are more susceptible to adverse outcome after
closed-head injury than those expressing apoE3.29 Therefore,
a possible explanation for our results is that the patients who
had prestroke dementia also to a greater degree represented
the apoE4 genotype, thereby being more vulnerable to a
vascular insult such as stroke.
The well-documented impact of AF on the prognosis of
first-ever stroke7–9 is confirmed in this investigation. Heart
failure was also a significant predictor of stroke severity and
case fatality. From earlier studies, it is known that patients
with signs of cardiac failure have worse short time surviv-
al.10 –12 It is also known that patients with dilated cardiomy-
opathy have a high incidence of left ventricular thrombus
formation and are at increased risk of embolic complica-
tions.30 There is less information regarding the risk of
systemic emboli in patients with decreased ventricular func-
tion from coronary artery disease, although in the Framing-
ham study, heart failure was ranked second in cardiogenic
stroke risk, with a 2- to 3-fold relative risk.6 Some promising
results exist regarding the use of warfarin in patients with
heart failure.31 At present, there are proposals for 2 new
studies, Warfarin and Antiplatelet Therapy in Chronic Heart
Failure (WATCH) and Warfarin Versus Aspirin in Reduced
Cardiac Ejection (WARCEF), to compare warfarin and anti-
platelet agents in patients with low ejection fraction. The
pooled data will provide sufficient power to determine
whether warfarin reduces stroke risk in patients with low
ejection fraction.32
Age was not a significant predictor of stroke severity or
short-term survival, which is in line with previous studies33,34
showing that age is not an independent risk factor for early
death after stroke. The impact of age on mortality seems to
rise after a year.12
To the best of our knowledge, it has not been shown before
that living alone is a risk factor for short-term mortality. One
previous study found an association between marital status
and 1-month survival in univariate but not multivariate
analysis.12 A recently published study showed that if patients
had negative attitudes toward their illness, they did not
survive as long as other patients.35 Although that study and
others evaluating psychological measures often aim at long-
term survival, it is possible that the same factors, ie, fatalism
and helplessness or hopelessness, which were significant
predictors in the before-mentioned study,35 also influence
short-term survival.
A history of arterial hypertension was found in 36% of our
patients. Our figure is somewhat lower than the registries
used for comparison, which may be due to regional or secular
trends, different diagnostic criteria, or different case finding
procedures. Prestroke hypertension did not involve a worse
prognosis; rather, the contrary is true when it comes to case
fatality, although the significance is borderline. Although this
relationship has to be confirmed, patients with hypertension
may benefit in some way from their higher blood pressure in
the acute phase. This, we think, stresses the importance of
avoiding decreases in blood pressure in the acute phase, eg,
through liberal administration of intravenous fluids.36 In
previous studies, prestroke hypertension has not had any
significant beneficial influence on short-term mortality.37 In
some studies, high blood pressure on admission has even
been shown to be an adverse factor.17 This suggests that high
blood pressure on admission does not need to reflect a
prestroke hypertension or vice versa.
Because measuring the level of blood lipids is not a part of
routine medical examination at health centers in Örebro, the
impact of prestroke cholesterol levels could not be studied.
We do not think that this has had a significant effect on the
results. The effect of cholesterol on stroke prognosis seems
 Appelros et al
small. Although 1 retrospective study has shown that higher
serum cholesterol concentrations were associated with re-
duced long-term mortality after stroke,38 other studies have
shown no effect.
The outcome of a multivariate analysis is strongly affected
by the independent variables used. They should be clinically
and intuitively relevant.39 Although statistics cannot tell
whether something is a confounder or an intervening variable,
the ability of multivariate analysis to simultaneously assess
the independent contribution of a number of risk factors is
particularly important when there are confounders. Whether a
variable is a confounder or just intervening is a decision that
has to be made on the basis of prior research and biological
plausibility.40 We have shown that there is significant corre-
lation between heart failure, AF, and prestroke dementia on
one side and stroke severity on the other. Therefore, when we
assess risk factors for case fatality, it is questionable whether
prestroke risk factors and different manifestations of stroke
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severity should be included in the same analysis, because
these 2 groups of factors reflect different phases in the disease
development. In spite of this, we performed such an analysis
to show the effect. As expected, this analysis showed that the
impact of the most powerful predictors of stroke severity
(heart failure and AF) were out-leveled, whereas dementia,
which had less impact on stroke severity, was still significant.
Evaluation of the prestroke risk factors was done at the
time of the stroke diagnosis, not prospectively. That may
have led to some underestimation of the prevalence of risk
factors rather than the contrary. We do not think that this
jeopardizes the validity of the study, because most likely
milder forms of risk factor conditions that have escaped
prestroke discovery are in question. The only way to achieve
prospective data collection for purposes like our study is
through large longitudinal cohort studies, which are time
consuming and costly but would certainly be desirable to
confirm our results.
With a community-based stroke incidence study design,
this investigation has shown that AF, heart failure, and
prestroke dementia are risk factors for having a severe stroke,
as well as for death within 1 month of a stroke event. Living
alone was also a risk factor for early death after stroke. If
confirmed by other studies, this knowledge may be translated
into primary and secondary prevention measures. There may
be great potential in finding and giving primary prophylaxis
to certain high-risk groups of patients such as patients with
AF or heart failure.
Acknowledgments
This study was supported by grants from the Research Funds of
Örebro County Council. We are grateful to Professor Matti Viitanen
for his valuable comments on the manuscript and to Anders
Magnusson, BSc, for statistical advice.
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 Predictors of Severe Stroke: Influence of Preexisting Dementia and Cardiac Disorders
Peter Appelros, Ingegerd Nydevik, Åke Seiger and Andreas Terént

Stroke. 2002;33:2357-2362
doi: 10.1161/01.STR.0000030318.99727.FA
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