Decreased Severity of Brain Infarct Can in Part Explain the

Decreasing Case Fatality Rate of Stroke

Heikki Numminen, MD; Markku Kaste, MD; Kari Aho, MD; Olli Waltimo, MD; Mervi Kotila, MD

Background and Purpose—Case fatality rates for stroke has declined in most Western industrialized countries during
recent decades. One possible explanation for this is a decrease in the severity of stroke symptoms. We therefore sought
evidence for a change in stroke severity and its relationship with case fatality rates.
Methods—We compared the severity of symptoms among first-ever stroke patients in 2 population-based prospective
stroke registers maintained during 1972 to 1973 and 1989 to 1991 in Finland. Patients who were evaluated by study
assistants or the investigator during the first week after the onset of symptoms were included in the study, and their
severity of symptoms was assessed with the use of comparable scales modified from the Scandinavian Stroke Scale.
Results—A total of 244 and 594 patients were registered, and a portion of them (155 [63.5%] and 360 [60.6%]) were
included in the analyses in the registers for Espoo-Kauniainen from 1972 to 1973 and for 4 separate districts in Finland
from 1989 to 1991, respectively. The death rates during the first week among those who were not included did not differ
between the registers. The severity of symptoms decreased significantly between the registers in both patients with brain
infarct or intracerebral hemorrhage but not in those with subarachnoid hemorrhage. The severity of symptoms was an
independent factor of case fatality at 1 month.
Conclusions—The severity of symptoms of brain infarcts has decreased and can in part explain the decreased case fatality
rate of stroke in Finland. However, the change in patients with intracerebral hemorrhage may be overestimated due to
undiagnosed intracerebral hemorrhages in the first register resulting from the lack of brain CT. (Stroke.
2000;31:651-655.)
Keys words: cerebrovascular disorders 䡲 treatment outcome 䡲 mortality 䡲 prospective studies

T he stroke mortality rate in Finland has declined steadily

since 1965 in men and since 1955 in women,1 which is
typical for most Western industrialized countries.2–5 This has
occurred despite a stable incidence rate during the 1980s. The
decreasing case fatality rates reported in the same studies3–5
are the most likely cause of this.
At least 3 explanations for the observed decrease in case
fatality rates have been suggested: (1) enrollment bias during
registration includes patients with milder strokes during
subsequent years, (2) better supportive and rehabilitative care
of acute stroke patients may have decreased the case fatality
rate, and (3) the symptoms of acute stroke could have become
milder, leading to increased survival rates.
To evaluate the impact of stroke symptoms, a valid method
for the assessment of stroke severity is necessary. A retro-
spective method used in previous studies,6 –11 which suggests
that strokes are less disabling at the present than they were
previously, may be too inaccurate or insensitive for this
purpose. The present method, which is based on a prospec-
tively used standard scale to evaluate the severity of symp-
toms modified from the Scandinavian Stroke Scale, avoids
the difficulties involved in the previous studies. The aim of
the present study was to compare the severity of stroke in 2
population-based registers during 1972 to 1973 and 1989 to
1991 in Finland and to determine the relationship between
stroke severity and case fatality.
Subjects and Methods
The study area, population, case finding, and case ascertainment for
the 2 registers have been published previously.5,12 The first register
covered a semiurban area, Espoo-Kauniainen, from 1972 to 1973
(EK 72–73).12 The second register was maintained from 1989 to
1991 in 4 separate rural districts in Finland (FHA 89 –91).5 The mean
study population consisted of 113 100 and 134 804 inhabitants in the
EK 72–73 and FHA 89 –91 register regions, respectively. All
patients with first-ever stroke and aged ⱖ15 years were registered
and evaluated by the study assistants for the FHA 89 –91 register5 or
the investigator for the EK 72–73 register.12 The registers were
maintained according to the guidelines of the World Health Organi-
zation (WHO) Stroke Register.13
The Scandinavian Stroke Scale14 was used for assessment of
stroke severity in the FHA 89 –91 register. It has a 4-grade scale for
the evaluation of consciousness and a 5-grade scale for the evalua-
tion of motor function in the arm and leg (Table 1). The WHO Stroke
Register form, which assesses consciousness with a 4-grade scale,

Received September 15, 1999; final revision received December 2, 1999; accepted December 2, 1999.
From the Department of Clinical Neuroscience (H.N., M.K., O.W., M.K.), Helsinki University Central Hospital, Helsinki, Finland; and Department
of Neurology (K.A.), Jorvi Hospital, Espoo, Finland.
Correspondence to Dr Heikki Numminen, Department of Clinical Neuroscience, Helsinki University Central Hospital, PL 300, 00029 HYKS, Helsinki,
Finland. E-mail h.numminen@kimpinen.fimnet.fi
© 2000 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

651
652 Stroke March 2000

TABLE 1. Severity Score With Original Descriptions of TABLE 2. Proportion of Number of Deaths of Stroke Patients
Definitions Used for Conversion of Patient Status in Included in Analyses and Case Fatality at 1 Month After Onset
EK 72-73 Register and Scandinavian Stroke Scale Used in of Stroke According to Stroke Subtype and Gender
FHA 89-91 Register
EK 72-73 FHA 89-91
EK 72-73 FHA 89-91
Stroke Case Case
Consciousness Subtype Patients, n Fatality, % Patients, n Fatality, %
6 Fully conscious Fully conscious BI 22/105 21.0 42/304 13.8
4 Somnolent Somnolent, can be awakened to Men 11/56 19.6 14/138 10.1
full consciousness
Women 11/49 22.4 28/166 16.9
2 Semicoma Reacts to verbal command but is
not fully conscious ICH 8/15 53.3 5/40 12.5

0 Coma Unconscious Men 1/5 20.0 5/26 19.2

Eye movements Women 7/10 70.0 0/14 0.0

4 No gaze palsy No gaze palsy SAH 8/31 25.8 4/13 30.8

2 Gaze palsy Gaze palsy present Men 0/5 0.0 1/3 33.3

0 Conjugate eye deviation Women 8/26 30.8 3/10 30.0

䡠䡠䡠
Arm power NS stroke 0/4 0.0 1/3 33.3

6 Normal strength Raises arm with normal strength Men 0/3 0.0 0/1 0.0

5 Raises arm with reduced strength Women 0/1 0.0 1/2 50.0
䡠䡠䡠
4.5 Raises arm or Total 38/155 24.5 52/360 14.4
䡠䡠䡠
reduced strength Men 12/69 17.4 20/168 11.9
4 䡠䡠䡠 Raises arm with flexion in elbow Women 26/86 30.2 32/192 16.7
2 Can move, but Can move but not against gravity NS indicates nonspecific.
cannot raise arm
0 No movement Paralysis (infarct versus other types), and register (time period). Case fatality
Leg power rates were also compared between the registers in subgroups of
6 Normal strength Raises leg with normal strength patients with brain infarcts (BIs): those with more severe symptoms
(severity score 0 to 10), with moderate symptoms (severity score
5 䡠䡠䡠 Raises leg with reduced strength 10.5 to 19.5), and with milder symptoms (severity score 20 to 22).
4.5 Raises leg or 䡠䡠䡠 In the FHA 89 –91 register, conventional risk factors were rec-
reduced strength orded. Regression analysis was used to estimate the association of
4 Raises leg with flexion of knee risk factors with the severity score. The available risk factors
䡠䡠䡠
included treated hypertension, coronary heart disease, heart failure,
2 Can move, but Can move but not against gravity atrial fibrillation, diabetes, and smoking. A combined factor, cardio-
cannot raise leg vascular disease, was constituted if either hypertension, coronary
0 No movement Paralysis heart disease, or heart failure was present. Other factors that were
evaluated included age, sex, subtype of stroke, and the Rankin scale
score to measure independence in activities of daily living before the
was used in the EK 72–73 register. In addition, a 5-grade scale for onset of stroke.
the separate evaluation of motor function in the arm and leg was used
in this register. It was possible to convert the raw data recorded in the Results
EK 72–73 register to comparable values in the Scandinavian Stroke
Scale (Table 1). In estimation of the severity of stroke, we used only
A total of 244 and 594 patients with first-ever strokes were
level of consciousness, eye movements, and arm and leg power, included in the EK 72–73 and FHA 89 –91 registers, respec-
which are known to correlate with case fatality.15 After these values tively, and a portion of them (155 [63.5%] and 360 [60.6%]
were totaled, they constituted the score used to assess the severity of patients, respectively) were investigated within 1 week after
stroke. This severity score has a minimum of 0 points and a the onset of stroke and included in the analyses. Table 2
maximum of 22 points (from the most severe to the mildest stroke),
which corresponds to the prognostic score used in the Scandinavian
presents their number and case fatality according to stroke
Stroke Scale. Only patients who were registered and evaluated subtype and sex. The mean ages were 64.0 and 69.8 years for
during the first week after the onset of stroke symptoms were men and 64.5 and 75.3 years for women in the EK 72–73 and
included in the analyses. FHA 89 –91 registers, respectively. In the EK 72–73 register,
The severity scores are expressed as age-adjusted mean values and 15.2% (37 of 244) of the patients were excluded due to death
95% CIs. We used ␹2 tests with continuity correction (Statview;
Abacus Concepts) and the exact test (Egret; Statistics and Epidemi- during the first week and 21.3% (52 of 244) were excluded
ology Research Corporation) to calculate differences in proportions. due to a delay in evaluation; respective values for the FHA
An ANOVA (SuperAnova; Abacus Concepts), with age as a covari- 89 –91 register were 11.3% (67 of 594) and 28.1% (167 of
ate, was used to evaluate the differences in severity scores between 594) (difference in death rates 3.9%, 95% CI ⫺1.3% to 9.1%,
the registers. The strength of association between the severity score ␹2⫽2.06, P⫽0.152).
and case fatality was analyzed with linear regression (Statview).
Multiple logistic regression (Egret) was used to estimate the effect of The severity score for all strokes has increased slightly (ie,
various factors on case fatality rates. Factors used in these analyses strokes have become milder since 1973) (Table 3). The
included patient age and sex, severity score, subtype of stroke change was seen in BIs and intracerebral hemorrhages (ICHs)
 Numminen et al Severity of Brain Infarcts Has Decreased 653

TABLE 3. Age-Adjusted Mean of Severity Score (95% CI) were 44% (34 of 77), 6% (6 of 96), and 2% (2 of 131).
According to Stroke Subtype and Gender and P Values for Despite the differences, the exact test did not show any
Significance of Difference Between Registers significance in case fatality rate at 1 month between the
EK 72-73 FHA 89-91 P registers (odds ratio 1.41, 95% CI 0.68 to 2.91, P⫽0.41).
Because changes in stroke risk factors during recent
BI 13.3 (12.0–14.6) 15.5 (14.8–16.3) 0.004
decades have been associated with decreased stroke mortality
Men 13.6 (11.9–15.4) 16.7 (15.6–17.8) 0.004
rates, we wanted to analyze whether the presence of risk
Women 13.1 (11.2–15.1) 14.6 (13.5–15.6) 0.198 factors was associated with the severity of symptoms among
ICH 7.5 (3.7–11.3) 14.9 (12.7–17.1) 0.001 patients in the FHA 89 –91 register. However, only patient
Men 8.7 (1.1–16.4) 14.2 (11.8–16.7) 0.078 age (slope ⫺0.12, 95% CI ⫺0.17 to ⫺0.07, P⬍0.001,
Women 6.5 (0.8–12.3) 16.4 (11.8–21.0) 0.008 r2⫽0.06) and the Rankin scale score (slope ⫺1.86, 95% CI
SAH 17.1 (14.2–19.9) 14.6 (9.8–19.4) 0.358 ⫺2.45 to ⫺1.28, P⬍0.001, r2⫽0.10) before the onset of
Men 17.8 (12.5–23.2) 10.3 (0.0–21.2) 0.072 stroke were significantly associated with the severity of
stroke symptoms in a simple linear regression. Neither the
Women 16.8 (13.7–20.9) 16.1 (10.3–21.9) 0.818
stroke subtype nor the presence of cardiovascular disease or
NS stroke 16.6 (8.8–24.4) 3.5 (0.0–15.7) 0.025
atrial fibrillation recorded at the onset of stroke was shown to
Men 19.0 (5.4–32.6) 6.0 䡠 䡠 䡠 0.289 be a significant factor.
Women 10.0 䡠 䡠 䡠 2.0 䡠 䡠 䡠 䡠䡠䡠
Total 13.4 (12.2–14.5) 15.4 (14.7–16.2) 0.002 Discussion
Men 13.9 (12.3–15.5) 16.1 (15.1–17.1) 0.025 The severity of stroke symptoms among patients with their
Women 12.9 (11.3–14.4) 14.9 (13.9–15.9) 0.038 first-ever stroke has declined between 1973 and 1991 in
Finland (ie, the essential signs of stroke, including motor
NS indicates nonspecific.
hemiparesis, gaze paresis, and disturbed consciousness, are
now milder than during previous decades); however, this
but not in subarachnoid hemorrhages (SAHs). The increase in change concerns only patients with BI and ICH. The change
severity score is slightly less in females than in males with BI. is overestimated in patients with ICH for methodological
The severity score is strongly associated with case fatality reasons discussed later. The results also show that the severity
(slope 0.028, 95% CI 0.024 to 0.032, P⬍0.001, r2⫽0.27) of stroke symptoms is a significant contributor to case fatality
throughout the patient population (n⫽515). rate. In addition, the results indirectly support the hypothesis
Table 4 presents the factors associated with case fatality that better management of patients with BI could be another
rates for all strokes at 1 month after onset. In addition to the independent factor in case fatality rate.
increase in severity score (ie, less severe stroke), low age, and Our results rely on the appropriate conversion of the
having a stroke later (ie, included in the FHA 89 –91 register) severity scores into a modified Scandinavian Stroke Scale.
were independently associated with decreased case fatality We believe that the converted scores represent the original
rates. When only BIs were included in the analysis, having a symptoms of patients as exactly as possible and thus are
stroke between 1989 and 1991 (ie, included in the FHA reliable, although the scales used were not originally the
89 –91 register) remained an independent factor even after same. The assessment of stroke severity in both registers has
adjustments to the severity score and patient age (Table 4). To occurred prospectively and simultaneously with the enroll-
analyze whether inclusion in the FHA 89 –91 register had any ment of patients by study assistants5 or the investigator.12 In
effect on case fatality rates in different subgroups of patients addition, the conversion of scores was performed inflexibly
with BIs, these patients were stratified according to their with a microcomputer with the algorithm described in Table
severity score. Case fatality rates for BI patients in the EK 1 without a review of medical records. The appropriate
72–73 register were 50% (16 of 32), 9% (5 of 57), and 6% (1 conversion of scales is supported by the observation that
of 16) in the groups of severe, moderate, and mild symptoms, neither the severity score in patients with SAH in the present
respectively. In the FHA 89 –91 register, the respective values study nor case fatality rates throughout the study population
of these patients5 changed. This is in agreement with the
TABLE 4. Effect of Various Factors on Case Fatality at 1 results of another Finnish study, in which the 3-week case
Month in Multiple Logistic Regression Analysis in All Patients fatality rates remained stable from the 1970s to the 1980s
and in Patients With BI despite an intensified neurosurgical treatment policy16 that
favored the hypothesis of a disastrous unchanged course in
All Patients Patients With BI
SAH, which was also observed at the Mayo Clinic.17
OR 95% CI OR 95% CI One probable bias arose from the use of brain computed
FHA 89-91 0.39 0.21–0.71 0.38 0.21–0.69 tomography, which was not available at the time of the EK
72–73 register, as a diagnostic tool. In the FHA 89 –91
Age/1 y 1.03* 1.01–1.06 1.02* 1.00–1.05
register, a CT scan was performed for 60% of patients. This
Male sex 0.70 0.39–1.24 0.70 0.39–1.23
naturally led to increased sensitivity in finding patients with
Stroke other than infarct 1.91 0.95–3.83 䡠䡠䡠 䡠䡠䡠 a small ICH. Thus, the advent of cranial imaging might
Severity score/1 point 0.83* 0.79–0.86 0.82* 0.79–0.86 explain at least in part the changes in case fatality rates related
*Change in the risk for death per unit change in the variable. to ICH. We argue, however, against the possibility that this
654 Stroke March 2000
could also be the reason for the observed decrease in severity
of symptoms among patients with BI, because patients with
low severity scores (ie, severe stroke resulting from the ICH)
were also most likely diagnosed in the first register, whereas
the patients with slight symptoms and an undiagnosed ICH in
the first register could have diluted the trend observed among
patients with BI. The argument supporting this judgment is
the fact that in the FHA 89 –91 register, the mean severity
score among patients with ICH was almost as high as the
mean severity score among patients with BI. The BI results
thus appear reliable, but those for ICH include bias due to the
diagnostic differences between the registers.
Bias in patient registration is an unlikely reason for our
results, because most of the patients enrolled in both registers
were hospitalized during the acute phase of their stroke (89%
and 86% in the EK 72–73 and FHA 89 –91 registers,
respectively), and in both time periods, all patients with
severe strokes were hospitalized. The possibility, however,
that more patients with mild strokes, especially BIs, were
included in the FHA 89 –91 register than in the EK 72–73
register cannot be ruled out. This is unlikely, however,
because the incidence of BI in the FHA 89 –91 register has
not increased compared with the previous register; on the
contrary, it has decreased slightly.5 In addition, the case
fatality rates during the first week among the patients not
included in the present analysis did not differ significantly
between the registers, supporting the fact that mild strokes in
both registers are registered with equal frequency within the
first week after the onset of stroke.
In the few studies that evaluated trends in the severity of
stroke,6 –11 the assessment of symptoms was made retrospec-
tively from medical records, which may have lead to either
inaccuracy or insensitivity in the results compared with the
present method. All of the investigators reached the same
conclusion, however: the severity of stroke has declined
during recent decades. The earliest observation is from the
Framingham cohort, in which a significant increase in fre-
quency of mild deficits was found from the 1950s to the
1970s.6 In the Minnesota Heart and Stroke Survey, the
decreasing frequency in various stroke symptoms among
hospitalized patients continued throughout the 1970s and
1980s.7,9 The WHO Monica project in northern Sweden also
draws the conclusion that the proportion of patients with
extensive motor deficits has declined during the late 1980s.8
Thus, the present prospective study confirms these earlier
retrospective observations.
What are the reasons for the decreasing severity of symp-
toms? One possible explanation could be better general health
of the population today than 2 decades ago. Reduction in the
rate of stroke risk factors could be another reason. In all
probability, changes in risk profile may in part be involved in
the decreased mortality rates for stroke. In a recent publica-
tion from Finland, changes in conventional risk factors during
the 1970s and 1980s could predict 71% of the observed fall in
mortality rates for stroke in men and 54% of the fall in
women.18 Although we were not able to compare changes
between risk factors and case fatalities in the previous study,
no association between the case fatality rate at 1 month and
the cardiovascular risk factors could be found throughout the
FHA 89 –91 population,5 nor could any association be found
in the present study between the cardiovascular risk factors
and the severity of symptoms in all strokes. A similar
conclusion could be drawn in a more detailed risk factor
registration.19 Thus, the risk factors appear to play a minor
role both in the case fatality rate and in the severity of
symptoms when age, the subtype of stroke, and patient
premorbid condition are accounted for.
Did medical treatment contribute to the decrease in stroke
severity? To date, no evidence is available that any drug
treatment, except thrombolytic therapy, which was not used
among the registered patients, could influence stroke symp-
toms during the acute phase. There is some evidence, how-
ever, that aspirin treatment can contribute to a reduction in
death and dependency caused by ischemic stroke in the long
term,20 and the Chinese Acute Stroke Trial suggested that
patients treated with aspirin could have a better early func-
tional outcome.21 The use of aspirin before the appearance of
SAHs could reduce the risk of ischemic complications.22 On
the other hand, neither a population-based study10 nor a
prospective survey23 that evaluated hospitalized stroke pa-
tients within 24 hours after admission could find any support-
ive evidence for the favorable effect of aspirin on the severity
of stroke. The use of anticoagulant or antithrombotic treat-
ment was not registered in the present study, and accordingly
this question cannot be evaluated, but this possibility must be
considered in future surveys.
The results of the logistic regression analysis show that in
addition to the severity of symptoms among patients with BI,
the time period of the register also exerted an independent
positive effect on case fatality rates. Whether this effect is
dependent on the above-mentioned possibilities of reducing
the rate of stroke risk factors and medical treatments or on
better prevention of complications and early rehabilitative
care of acute stroke patients cannot be answered here. The
lack of evidence for the association of stroke risk factors and
case fatality, as well as medical treatments and case fatality,
favors the assumption that better overall care of patients with
BI could also influence case fatality rates.
Our conclusion is that the severity of ischemic BI has
decreased and that this change could in part explain the
decrease in case fatality rates observed in Western countries
during the recent decades. Both the lack of any other evidence
for the decrease in case fatality rates and the finding of the
register time period as an independent factor contributing to
the case fatality rate indirectly support the role of better
patient care as another explanation for the decrease in case
fatality rates, which tallies with the observation of the Stroke
Unit Trialists’ Collaboration.24
Acknowledgments
This work was supported by the Finnish Heart Association. We
would like to thank Associate Professor Seppo Sarna for his
statistical assistance and Jaana Immonen, Seija Keskiväli, Eeva
Kröger, Pirjo Lyytikäinen, Marja-Liisa Niemi, Oona Tuomi-Nikula,
and Markku Karjalainen for registration of the patients.
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