Beruflich Dokumente
Kultur Dokumente
Neuroepidemiology 2009;33:254260
DOI: 10.1159/000229780
Department of Neurology and b Copenhagen City Heart Study, Bispebjerg Hospital, University of Copenhagen;
National Institute of Public Health, and d Department of Neurology, Rigshospitalet, National University Hospital,
Copenhagen, Denmark
Key Words
Stroke, long-term survival Cancer Cerebrovascular
disease Cardiovascular disease
Abstract
Background and Purpose: Only few have studied long-term
survival after stroke. Such knowledge is essential for the
evaluation of the current and future burden of stroke. The
present study presents up to 30 years of follow-up of patients after a first-ever stroke. Methods: Participants in the
Copenhagen City Heart Study who experienced a first-ever
stroke from 1978 to the end of 2001 were followed to the end
of 2007. Stroke events were validated using the World Health
Organizations definition of stroke. Linkage to the Danish
Civil Registration System enabled identification of participants who died before the end of 2007. The National Register
of Causes of Death provided cause of death. Survival in
stroke patients was compared with survival in participants
in the Copenhagen City Heart Study who did not suffer a
stroke, and with survival in the general Danish population.
Cox regression analyses adjusting for age and gender were
used to compare survival in six consecutive 4-year periods
starting with 19781982. Results: Of 2,051 patients with firstever stroke 1,801 died during follow-up. Causes of death
Introduction
Methods
The cohort was followed for 30 years. Details about the CCHS
have previously been published [911]. In brief, the CCHS was
initiated in 1976. A random sample of 19,698 Caucasian men and
women, selected after age stratification from the general populations of sterbro and Nrrebro in Copenhagen, were invited to
participate in the first study examination in 19761978. All participants were invited by letter to three later health examinations
in 19811983, 19911994, and 20012003. The response rates of
persons to the 4 examinations were 74, 70, 61, and 50%, respectively. At the health examination a questionnaire concerning history of stroke and risk factors for vascular disease was completed.
Data on stroke and death were obtained from public registers for
all members of the cohort, i.e. those who responded and non-responders.
Participants
In this cohort those invited to the first examination in 1976
1978 had a mean age of 56.0 years and those invited to the 4th
examination in 20012003 had a mean age of 61.2 years. The control group consisted of individuals from the CCHS cohort without stroke. Participants who experienced stroke before 1978 were
excluded from analysis. Information about first-ever stroke events
was obtained from 1978 and analyzed until the end of 2001. Information on causes of death was obtained until the end of 2006
and on vital status until the end of 2007.
The study was approved by the Danish Data Protection
Agency.
rized as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Events with no information on stroke
subtypes were recorded as unspecified stroke.
First time-ever events occurring during the period 1978 to the
end of 2001 were included. Participants with transient ischemic
attacks (TIAs) and retinal artery occlusion were excluded.
The Danish National Hospital Discharge Register provided
information on hospital admissions for all participants, responders as well as non-responders. This register used the International Classification of Diseases (ICD) codes of the 8th revision (430
438) from 1976 to 1993 and 10th revision (I60I69 and G45) after
January 1994 to describe the stroke events. The stroke diagnoses
were then validated from patients hospital records. Information
about non-hospitalized stroke patients were first obtained from a
positive self-reported stroke event at the study examination and
additional information was obtained from the patients general
practitioners.
Information on Time and Causes of Death
Information on time of death was obtained from 1978 to the
end of 2007 by record linkage to the Danish Civil Registration
System which contains information on all deaths in Denmark.
The National Register of Causes of Death, established by the National Board of Health in 1943 [13], contains all death certificates
and provided the causes of death until the end of 2006. The following ICD codes were used to define the cause of death: cerebrovascular diseases 430438 (ICD-8) and I60I69 (ICD-10); other
cardiovascular diseases 390429 and 440458 (ICD-8) and I00
I52 and I70I99 (ICD-10), and cancer 140209 (ICD-8) and C00
D09 (ICD-10), while the remainder were classified as other causes
of death. Patients who died without being hospitalized but received a stroke diagnosis were registered as fatal unspecified
strokes.
Bias
By validating the stroke diagnosis we discarded false-positive
cases. Except for those participants who at study examination reported having had a stroke for which they had not been admitted
to hospital, we were not in a position to detect false-negative cases. Among participants who reported having had a stroke for
which they had not been admitted to hospital and therefore were
not reported in the register, a diagnosis of stroke was confirmed
in approximately half of the cases. This amounted to about 10%
of those reporting having had a stroke. For persons who did not
respond to the invitation to the health examinations, approximately 1 of 3, we were unable to detect non-hospitalized stroke
events. We may thus have missed about 10% of stroke events in
this group equal to about 4% of the total number of stroke events.
Thereby we may have underestimated the number of strokes by
approximately 4%.
Study Size
The size of the cohort of 19,698 individuals was determined in
1976 as being suitable for epidemiological studies in cardiovascular disease [11]. At the second examination in 19811983 the cohort was expanded by a random sample of 500 men and women
aged 2024 years. At the third examination in 19911994, the cohort was expanded by 3,000 men and women aged 2049 years,
and at the fourth examination in 20012003 the expansion was by
1,040 persons aged 2029 years from the same area of the town.
Neuroepidemiology 2009;33:254260
255
Stroke
No stroke
Age <65
Age 6571
Age 7279
Age >79
Age <65
Age 6571
Age 7279
Age >79
1.0
Survival
0.8
0.6
0.4
0.2
0
0
10
15
20
25
30
Study
Years
19781981
19821985
19861989
19901993
19941997
19982001
Women
Men
age, years
age, years
110
128
159
147
237
214
66.7
68.2
72.7
72.1
75.8
77.7
180
175
182
154
187
178
67.2
68.0
68.0
70.9
71.5
74.3
Table 2. Relative risk of death (95% CI) for time period in a sexstratified Cox model adjusted for age at stroke onset
Period
First week
First month
After the
first week
19781981
19821985
19861989
19901993
19941997
19982001
1 (reference)
2.08 (1.223.55)
1.78 (1.043.04)
0.97 (0.521.79)
0.82 (0.451.50)
1.21 (0.692.11)
1 (reference)
1.24 (0.831.86)
1.39 (0.952.04)
0.79 (0.511.22)
0.76 (0.511.14)
0.81 (0.541.21)
1 (reference)
0.87 (0.731.04)
0.82 (0.690.98)
0.72 (0.600.86)
0.66 (0.550.79)
0.56 (0.460.68)
256
Neuroepidemiology 2009;33:254260
Results
19781981
19821985
19861989
19901993
19941997
19982001
1.0
Survival
0.8
0.6
0.4
0.2
0
0
10
15
20
25
14.2
15.0
15.4
16.2
16.7
17.6
9.5
10.5
10.9
11.8
12.4
13.5
5.4
6.2
6.5
7.3
7.8
8.8
2.6
3.1
3.3
3.8
4.2
4.9
1.1
1.3
1.4
1.7
1.9
2.3
Men
19781981
19821985
19861989
19901993
19941997
19982001
13.2
14.2
14.7
15.6
16.2
17.2
8.5
9.4
9.8
10.7
11.3
12.5
4.8
5.4
5.7
6.4
6.8
7.8
2.4
2.8
2.9
3.4
3.7
4.3
1.0
1.2
1.3
1.6
1.7
2.1
Fig. 2. Predicted survival for men aged 70 at the time of stroke for
257
0
1981
1982
1985
1986
1989
1990
1993
1994
1997
1998
2001
0
1978
1981
Age
50 years
60 years
70 years
80 years
90 years
0
1981
1982
1985
1986
1989
1990
1993
1994
1997
1986
1989
1990
1993
1994
1997
1998
2001
1994
1997
1998
2001
1982
1985
1998
2001
Stroke age
50 years
60 years
70 years
80 years
90 years
0
1978
1981
1982
1985
1986
1989
1990
1993
Fig. 3. Increase in remaining lifetime for 1-week survivors after stroke in women (b) and in men (d) from 1978
to the end of 2001. The left-hand side shows the increase in remaining lifetime for the entire Danish population
(a, c) from 1981 to the end of 2001.
Discussion
Neuroepidemiology 2009;33:254260
Ischemic stroke
Unspecied stroke
Intracerebral hemorrhage
Subarachnoid hemorrhage
1.0
0.8
Survival
0.6
0.4
0.2
0
0
10
15
20
25
30
type.
were admitted to a number of different services not reporting stroke severity. Neither could we adjust for other
risk factors such as atrial fibrillation, diabetes, smoking,
socioeconomic status, etc., due to inclusion of patients
who did not respond to our invitation. It is also a limitation that most of the stroke diagnoses were obtained
through registers and not hot pursuit. Some stroke
events may have escaped detection due to the limited access to false-negative cases. Among those who did not
respond, patients who were not admitted for their stroke
were not detected, which may amount to approximately
4% of all stroke events in the cohort. The large number of
unspecified strokes is due to insufficient diagnostic capability in the early years of this study.
The strength of this study is its large, well-defined
population-based design, and its length of follow-up.
Stroke events were validated prospectively with uniformity of standardized diagnostic criteria. First-ever stroke
events in participants who responded as well as those
who did not respond were included in this study through
public databases. Each positive diagnosis was validated
from patient hospital records. In responders, also nonfatal non-hospitalized stroke patients were included by
asking either the participants at the study visits or their
general practitioners.
Interpretation
Our results of improved long-term survival after
stroke are in agreement with other studies [1621]. The
improvement may be related to less severity of the strokes,
to increased awareness of stroke in the population, to implementation of stroke units, to better secondary prevention, and to increased life expectancy in the population
as a whole.
Generalizability
Our cohort represents a city population with documented reduced life expectancy compared to the remaining Danish population [29]. Previous studies from CCHS
[911] have documented a high rate of smoking and a
relatively low socioeconomic status both of which may
contribute to unfavorable long-term survival. Our results
may be generalizable to other city populations.
Acknowledgement
We thank Merete Appleyard for her excellent data management throughout the entire study period.
The Copenhagen City Heart Study is supported mainly by the
Danish Heart Foundation.
Neuroepidemiology 2009;33:254260
259
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