000342652

Original Paper
Cerebrovasc Dis 2012;34:272–281
DOI: 10.1159/000342652
Received: February 6, 2012
Accepted: August 13, 2012
Published online: October 20, 2012
Stroke and Transient Ischemic Attack
Incidence Rate in Spain: The IBERICTUS
Study
Jaime Díaz-Guzmán a Jose-A. Egido b Rafael Gabriel-Sánchez d
Gloria Barberá-Comes f Blanca Fuentes-Gimeno e Cristina Fernández-Pérez c
on behalf of the IBERICTUS Study Investigators of the Stroke Project of the
Spanish Cerebrovascular Diseases Study Group
a
Stroke Unit, Neurology Department, University Hospital Doce de Octubre, Complutense Faculty of Medicine,
Stroke Unit, Neurology Department and c Clinical Epidemiology Unit, University Hospital Clínico San Carlos,
d
Investigation Unit, University Hospital La Paz and CEIIS, and e Stroke Centre, Department of Neurology,
Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ Health Research Institute, Madrid, and
f
Medical Department for Thrombosis, Sanofi-Aventis, Barcelona, Spain
b
Abstract
Background: In Spain, stroke is a major public health concern, but large population-based studies are scarce and date
from the 1990s. We estimated the incidence and in-hospital
mortality of stroke through a multicentered populationbased stroke register in 5 geographical areas of Spain, i.e.
Lugo, Almería, Segovia, Talavera de la Reina and Mallorca,
representing north, south, central (!2) and Mediterranean
areas of Spain, respectively, the aim and novelty being that
all methodologies were standardized, and diagnoses were
verified by a neurologist using neuroimaging techniques.
Methods: The register identified subjects 117 years of age
who suffered a first-ever stroke or transient ischemic attack
(TIA) between 1 January and 31 December 2006. Stroke and
TIA were defined according to the WHO criteria. The Lau-
© 2012 S. Karger AG, Basel
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E-Mail karger@karger.ch
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sanne Stroke Registry definitions were used to classify ischemic stroke subtypes, as follows: (1) large-artery atherosclerosis (LAA); (2) cardioembolism (CE); (3) lacunar stroke or
small-artery occlusion (SAO); (4) stroke of other infrequent
cause (SIC), and (5) stroke of undetermined cause (UND). We
used several complementary data sources such as hospital
discharge registers, emergency room registers and primary
care surveillance systems. Results: In the 1-year study period, we identified 2,700 first-ever cerebrovascular episodes
(53% men; 2,257 strokes + 443 TIA episodes). Brain CT in the
acute stage was performed in 99% of cases. Of a total of
2,257 stroke patients, 1,817 (81%) had cerebral infarction, 350
(16%) had intracerebral hemorrhage, 59 (3%) had subarachnoid hemorrhage (SAH) and 31 (1%) had unclassifiable stroke.
The overall unadjusted annual incidence for all cerebrovascular events was 187 per 100,000 [95% confidence interval
(CI) 180–194; incidence for men: 202, 95% CI 189–210; incidence for women: 187, 95% CI 180–194]. The subtype of ischemic stroke could be determined in 1,779 patients and was
classified as LAA in 624 (35%), CE in 352 (20%), SAO in 316
Jaime Díaz-Guzmán, MD, PhD
Stroke Unit, Neurology Department, University Hospital Doce de Octubre
Complutense Faculty of Medicine
Avda Córdoba s/n, ES–28045 Madrid (Spain)
E-Mail jdiaz.hdoc @ salud.madrid.org
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Key Words
Epidemiology ⴢ Stroke ⴢ Incidence ⴢ Transient ischemic
attack ⴢ Subarachnoid hemorrhage
Copyright © 2012 S. Karger AG, Basel
Introduction
cidence of ischemic attack and hospital deaths from
stroke in the Spanish population. The data were derived
from 5 geographically disparate areas of Spain.
Materials and Methods
Study Design and Population
IBERICTUS is a prospective, population-based study aimed at
identifying all first stroke and transient ischemic attack (TIA)
events in Spain. The study accessed the data on stroke and TIA
recorded in 5 major cities, namely Lugo, Almería, Segovia, Talavera de la Reina and Mallorca, representing north, south, central
(!2) and Mediterranean areas of Spain, respectively, with care
provision for 1,440,979 citizens. Data sources, procedures and
stroke definitions have been described in detail elsewhere [5]. In
brief, we included all the cases presenting within the period of the
study. The individuals were 117 years of age (with no upper age
limit) and had suffered a first episode of acute cerebrovascular
disease diagnosed by the attending neurologist. The geographical
areas were selected on the basis of our Spanish NHS data indicating possible differences in stroke incidence in the different regions. Also, these regions provided a minimum population size of
at least 100,000 persons per study site (table 1). The data on the
at-risk population in each province, as well as the overall study
area, were obtained from the official 2005 census of the Spanish
National Institute of Statistics [6]. The overall study population
totaled 1,440,979 individuals (online suppl. fig. 1; for all online
suppl. material, see www.karger.com/doi/10.1159/000342652).
The study was designed to meet the quality criteria proposed by
Malmgren et al. [7] and Sudlow and Warlow [8] for ‘ideal’ population-based studies.
The Ethics Committee (Institutional Review Board of the Segovia General Hospital) approved the study. Data were coded to
ensure patient anonymity.
Stroke is a major cause of mortality and long-term
disability, with important socioeconomic consequences.
According to the WHO, stroke is the second most common cause of mortality worldwide [1]. In the WHO Monitoring Trends and Determinants in Cardiovascular Disease Project, the attack rate was estimated at around
200/100,000 individuals per year [2]. Attack rates vary
considerably geographically and, as such, extrapolations
need to be made with caution [3].
Stroke is the second most common cause of death in
Spain overall, while it is the principal cause in women.
Despite this, there are few studies assessing its incidence;
all the studies to date have been local, with considerable
heterogeneity of methodology [4]. Compared to these
studies, the novelty and aims of the IBERICTUS study are
that it has the power to estimate epidemiological data simultaneously in 5 large patient populations. All patients
were diagnosed in the acute stroke phase by the attending
physician, and diagnoses were verified by specialist neurologists using neuroimaging technology.
Mortality due to stroke is thought to be high in Spain,
but the real impact is unknown. Various factors may account for this high mortality rate, including genetic and
socioeconomic factors and the quality of health care
available [3]. Reliable data on incidence rates are essential
in the planning of health care resource distribution. The
health care system in Spain is one in which the citizen has
the right to access health care which is free at the point of
delivery. Resource management, with minor variations,
is within the jurisdiction of the governments of the autonomous regions of Spain.
The IBERICTUS study is a population-based epidemiological registry that seeks to estimate the rates of in-
Definition of Stroke
Stroke and TIA were defined according to the WHO criteria
as ‘rapidly developing clinical symptoms and/or signs of focal,
and at times global (applied to patients in deep coma and to those
with subarachnoid hemorrhage) loss of cerebral function with
symptoms lasting 124 h (! 24 h for TIA) or leading to death, with
no apparent cause other than of vascular origin’ [9]. The diagnosis was made by the attending physician and verified by a neurologist. The data on stroke and TIA morbidity and mortality
were obtained from the hospitals’ admission department and discharge register, as well as the hospitals’ emergency department
registry and the primary health care registers.
The International Classification of Diseases (9th revision) was
used to identify events as subarachnoid hemorrhage (SAH; n =
430), intracranial hemorrhage (ICH; n = 431), other unspecified
ICHs (n = 432), occlusion and stenosis of precerebral arteries (n =
433), occlusion of cerebral arteries (n = 434), TIA (n = 435), acute/
other ill-defined cerebrovascular disease (n = 436/437) or late effects of cerebrovascular disease (n = 438).
An adapted version of the Lausanne Stroke Registry [10] was
used to classify the ischemic stroke subtypes as follows: (1) largeartery atherosclerosis (LAA); (2) cardioembolism (CE); (3) lacunar stroke or small-artery occlusion (SAO); (4) stroke of other
Stroke Incidence Rate in Spain
Cerebrovasc Dis 2012;34:272–281
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(18%), SIC in 56 (3%) and UND in 431 (24%). The incidence
rates per 100,000 (95% CI) standardized to the 2006 European population were as follows: all cerebrovascular events,
176 (169–182); all stroke (non-TIA), 147 (140–153); TIA, 29 (26–
32); ischemic stroke, 118 (112–123); intracerebral hemorrhage,
23 (21–26), and SAH, 4.2 (3.1–5.2). Incidence rates clearly increased with age in both genders, with a peak at or above 85
years of age. The in-hospital mortality was 14%. Conclusions: Our results show that the incidence of stroke and TIA
in Spain is moderate compared to other Western and European countries. However, it is expected that these figures
will change due to progressively aging populations.
Table 1. Study centers participating in the assessment and recruitment of cases
Segovia
(Castilla y León)
Talavera
Lugo
(Castilla La Mancha) (Galicia)
Mallorca
(Islas Baleares)
Almería
(Andalucía)
Population
131,535
127,508
313,673
647,036
221,227
Population density
citizens/km2
23
446
32
218
76
Geographic location
40°57ⴕN
4°10ⴕW
39°57ⴕ30ⴕⴕN
4°49ⴕ58ⴕⴕW
43°01ⴕN
7°33ⴕW
39°58ⴕ00ⴕⴕN
3°08ⴕ00ⴕⴕE
36°50ⴕN
2°27ⴕW
Climate
continental
Mediterranean
mild continental
continental oceanic
Mediterranean
subdesert
Mediterranean
Reference hospital
(‘hot pursuit’)
Hospital Provincial, Hospital Nuestra
Segovia
Señora del Prado
Hospital Costa de Burela
Complejo Hospitalario
Xeral-Calde, Lugo
Hospital Comarcal de
Monforte de Lemos
Complejo Asistencial Son Dureta
Hospital Son Llatzer
Hospital Joan March
Hospital General de Mallorca
Hospital Sant Joan de Deu
Hospital d’Alcudia
Fundación Hospital Manacor
Hospital General de Muro
Hospital
Torrecárdenas
Nearby general hospitals in
or out of the districts of study
0
1
1
0
2
Probability that some patients
were hospitalized outside the
catchment area
low
very low
very low
none
low
Primary care health registers,
3-monthly check
(‘cold pursuit’)
Sentinel Physician
Network
3 additional cases
(over 251)
Sentinel Physician
Network
0 additional cases
(over 209)
not done
not done
(over 832)
regional administration
primary care health register
7 additional cases
(over 985)
not done
(see text)
not done
(see text)
not done
(see text)
not done
(see text)
not done
(see text)
infrequent cause (SIC), and (5) stroke of undetermined cause
(UND). Ischemic strokes were classified by the attending physician mainly on the basis of case history, clinical examination and
risk factor profile. For various reasons such as, for example,
scarce clinical information, the ischemic stroke subtype was
defined as ‘not classified’ (NC). If CT scans had not been performed, the stroke type (ischemic or hemorrhagic) was also defined as NC.
To ensure the validity of the diagnosis of acute stroke assigned
in the hospital discharge register or death register, a reliability
study of interobserver agreement was conducted prior to the conduct of the IBERICTUS study. The kappa index of agreement between the participant observers was 0.72 [95% confidence interval
(CI) 0.68–0.77] for the classification of clinical type (as ischemic,
hemorrhagic or undetermined) and 0.62 (95% CI 0.57–0.68) for
the classification of etiology of the ischemic stroke (as LAA, CE,
SAO, SIC or UND) [11]. The proportion of cases in the registry
that had not had a brain CT at the time of diagnosis was only 0.9%.
Statistical Analyses
Stroke incidence is reported as age-unadjusted and standardized rates according to the Spanish and European standard population using the direct method [12, 13]. The incidence rates and
274
Cerebrovasc Dis 2012;34:272–281
the respective 95% CIs were calculated using normal approximation to the binomial distribution. We employed one-way ANOVA
for the comparison of means. The EpiDat 3.1 and SPSS for Windows (version 14.0) statistical packages were used throughout.
Results
Between 1 January and 31 December 2006, 2,700 first
cerebrovascular events (2,257 strokes and 443 TIAs) were
identified in individuals aged 117 years (254 cases in Segovia, 209 in Talavera, 832 in Lugo, 992 in Mallorca, 413
in Almería). The hospitalization rate for stroke was
2,086/2,257 (92.4%), and for TIA, it was 126/443 (28.4%).
Table 2 shows the sociodemographic characteristics
and clinical assessment of patients in the study sample.
The mean 8 SD age of the patients was 73.9 8 13.4 years,
with a range of 18–101 years. The patients were older in
Segovia, Talavera and Lugo than in Mallorca and Almería
(p ! 0.05). Women represented 47% of the patients (aged
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Detected via death certificate
scrutiny
(over 413)
Table 2. Patients’ characteristics and methods of assessment in the IBERICTUS study
Source of information, %
Discharge reports/clinical history
Emergency reports/primary care
Women, %
Age, years1
Length of in-hospital stay, days1
CT scanning performed in acute stage, %
Type of stroke, %
Ischemic
Hemorrhagic
TIA
Undetermined
In-hospital mortality, %
1
IBERICTUS
(n = 2,700)
Segovia
(n = 254)
Talavera
(n = 209)
Lugo
(n = 832)
90.1
9.9
46.6
73.98813.39
10.9814.36
99.1
71.7
20.3
47.6
76.21812.73
9.33816.53
96.5
79.4
98.8
20.6
1.2
49.8
48.2
76.72811.34 75.96812.36
9.66812.94 13.08814.91
94.3
100
91.5
85.7
8.5
14.3
45
45
72.05814.08 71.86814.04
10.59815.20 8.9588.85
99.7
100
67.3
15.1
16.4
1.1
11.6
61.8
15
17.7
5.5
14.2
63.2
16.7
13.9
6.2
14.8
70.4
13.9
15.3
0.4
9.8
68.1
15.9
16
0
15.1
Mallorca
(n = 992)
Almería
(n = 413)
63.7
16
20.3
0
5.8
Mean 8 SD.
Table 3. Age- and gender-specific unadjusted annual incidence rates of first-ever stroke (including TIAs) per 100,000 population and
in-hospital mortality
Number
of men
at risk
Incidence, men
n
rate, %
18–24
25–34
35–44
45–54
55–64
65–74
75–84
>84
77,182
152,612
141,453
115,177
88,997
73,496
49,815
13,218
2
12
50
110
211
361
505
191
Total
711,950
1, 442
Age
group
years
Incidence, women
95% CI
Number
of women
at risk
Incidence, total
95% CI
Total
number
at risk
n
rate, %
n
rate, % 95% CI
2.6
7.9
35.3
95.5
237.1
491.2
1,013.8
1,445.0
0–6.2
3.4–12.3
25.5–45.1
77.7–113.4
205.1–269.1
440.5–541.9
925.3–1102.2
1,240.1–1,649.9
73,060
140,843
134,070
109,525
90,264
84,106
69,814
27,347
2
12
29
39
103
217
484
372
2.7
8.5
21.6
35.6
114.1
258.0
693.3
1,360.3
0–6.5
3.7–13.3
13.8–29.5
24.4–46.8
92.1–136.1
223.7–292.3
631.5–755
122.1–1,498.5
150,242
293,455
275,523
224,702
179,261
157,602
119,629
40,565
4
24
79
149
314
578
989
563
2.7
0.1–5.3
8.2
4.9–11.5
28.7
22.3–35
66.3
55.7–77
175.2 155.8–194.5
366.7 336.8–396.6
826.7 775.2–878.2
1,387.9 1,273.3–1,502.5
202.5
189.4–210.1
729,029
1,258
172.6
1,440,979
2,700
163.0–182.1
187.4
180.3–194.4
In-hospital mortality, men
In-hospital mortality, women
In-hospital mortality, total
n
n
rate, %
95% CI
rate, %
95% CI
n
rate, % 95% CI
18–34
35–44
45–54
55–64
65–74
75–84
>84
0
3
8
20
23
66
42
0
6
7.3
9.5
6.4
13.1
22.0
0
0–12.8
2.2–12.3
5.3–13.6
3.8–9.0
9.9–16.2
15.3–28.6
0
1
5
10
26
37
73
0
3.4
12.8
9.7
12.0
7.6
19.6
0
0–10.2
1.6–24.1
3.7–15.7
7.4–16.6
5.2–10.1
15.1–24.1
0
4
13
30
49
103
115
0
5.1
8.7
9.6
8.5
10.4
20.4
0
0.1–10
4.0–13.5
6.1–13.0
6.1–10.9
8.4–12.4
16.7–24.2
Total
162
11.2
9.5–13.0
152
12.1
10.2–14.0
314
11.5
10.3–12.9
Stroke Incidence Rate in Spain
Cerebrovasc Dis 2012;34:272–281
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Age
group
years
100
TIA
90
Incidence rate (×100,000)
80
70
60
50
M
M
40
W
All
M
W
All
30
M
W
W
20
M
All
W
All M
W
All
All
10
0
Segovia
Talavera
Lugo
Mallorca
Almería
300
Incidence rate (×100,000)
Hemorrhagic stroke
Ischemic stroke
M
250
IBERICTUS
W
All
200
150
M
W
M
M
All
M
W
All
M
All
All
All
W
W
Almería
IBERICTUS
W
100
50
0
Segovia
76.9 8 12.8 years), and 53% were men (aged 71.4 8 13.3
years). Eighty percent of cases were 665 years of age. A
brain CT scan was performed in 2,676 patients (99.1%).
Of a total of 2,257 stroke patients, 1,817 (80.5%) had ischemic stroke, 350 (15.5%) had ICH, 59 (2.6%) had SAH and
31 (1.4%) had an NC type of stroke. TIA was diagnosed
in 16.4% of cases (table 2).
The subtype of ischemic stroke could be determined
in 1,779 patients according to the modified Lausanne
Stroke Registry criteria as follows: LAA in 624 (35%), CE
in 352 (20%), SAO in 316 (18%), SIC in 56 (3%) and UND
in 431 (24%) patients.
The overall in-hospital mortality was 11% (314 patients). The fatality rates segregated by province were:
Segovia, 14% (95% CI 9.7–18.7%); Talavera, 15% (95% CI
9.8–19.9%); Lugo, 15% (95% CI 12.6–17.6%); Mallorca,
10% (95% CI 7.9–11.7%), and Almería 6% (95% CI 3.4–
8.2%). The in-hospital fatality rate was 11.2% for men and
12.1% for women (table 3), and it increased with age (on276
Cerebrovasc Dis 2012;34:272–281
Talavera
Lugo
Mallorca
line suppl. table 2). The mean length of hospitalization for
cerebrovascular disease was 11 8 14.8 days. Segregated
by stroke subtype, the fatality rate was 28% for ICH, 24%
for SAH, 13% for NC, 11% for ischemic stroke and 0.2%
for TIA.
The crude (unadjusted) annual incidence rate of firstever stroke was 187/100,000 (95% CI 180–194), and
age-standardized to the European population it was
176/100,000 (95% CI 169–182). The crude incidence rate
for men (202/100,000, 95% CI 189–210) was higher than
that for women (173/100,000, 95% CI 163–182; fig. 1).
After standardization to the European population, the
higher incidence rate for men remained statistically significant compared to that for women, i.e. 190 (95% CI
180–200) versus 159 (95% CI 150–168) per 100,000 (table 4).
The crude incidence rates according to stroke subtype
are shown in figure 2.
Díaz-Guzmán et al.
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Fig. 1. Crude incidence rates (!100,000
person-years) in the IBERICTUS study.
W = Women; M = men.
IBERICTUS
Segovia
Talavera
Lugo
rate
rate
95% CI
rate
95% CI
rate
163
137
151
132–193
108–165
130–172
130
135
134
102–159
107–163
114–154
126
119
124
99–153
93–146
105–143
110
119
116
37
17
27
22–51
7–28
18–36
93
90
92
95% CI
All cerebrovascular events
Men
190
180–200
Women
159
150–168
Total
176
169–182
All strokes (non-TIA)
Men
160
151–169
Women
131
123–140
Total
147
140–153
TIA
Men
30
26–34
Women
27
24–31
Total
29
26–32
Ischemic stroke
Men
128
119–136
Women
106
99–114
Total
118
112–123
ICH
Men
27
23–30
Women
18
15–21
Total
23
21–26
SAH
Men
3.1
1.8–4.4
Women
5.2
3.5–6.8
Total
4.2
3.1–5.2
Undefined
Men
2.4
1.2–3.5
Women
1
0.6–2.4
Total
2
1.2–2.7
Mallorca
Almería
95% CI
rate
95% CI
rate
95% CI
196
164
181
174–219
144–184
166–196
193
154
174
178–208
140–167
164–184
246
199
222
217–276
172–225
203–242
84–136
92–145
97–135
168
132
150
147–188
115–150
138–164
167
127
148
153–181
115–139
138–157
197
157
176
171–223
133–180
159–194
20
16
19
9–31
7–26
11–26
69
74
72
54–85
58–91
61–83
26
27
26.5
20–31
21–33
23–30
50
42
46
37–63
30–54
37–55
70–117
67–113
76–109
78
91
86
56–99
68–114
70–102
331
287
310
297–365
255–319
286–333
136
109
123
123–149
98–120
115–132
156
128
142
133–180
107–150
126–158
21
12
17
10–32
4–21
10–24
18
22
20
8–28
11–34
12–28
72
61
67
56–87
47–76
56–77
26
16
21
21–32
11–20
18–25
33
23
28
22–44
14–32
21–36
3.2
6.1
4.7
0–7.6
0.1–12.1
0.9–8.3
2.8
2.7
2.8
0–6.9
0–6.8
0–5.8
1.2
8.4
4.9
0–3.2
3.0–13.9
1.9–7.8
3.2
2.7
2.9
1.2–5.2
0.9–4.5
1.6–4.3
7.1
4.9
5.9
2.1–11.9
0.8–9.1
2.7–9.2
8
10
9
1–15
3–19
4–14
12
5
8
3–20
0–10
3–14
0
0
0
0
0
0
1.3
0
0.7
0.1–2.6
0
0.0–1.3
0
0
0
0
0
0
TIA and Stroke Ascertainment
Standardized population-based studies provide the
best source of information on stroke incidence and outcomes. We designed the study according to the quality
recommendations of Sudlow and Warlow [8], recently
updated to include large sample sizes in order to ensure a
sufficient number of incident strokes in 1 year and, in addition, to generate age-specific data on first-ever-in-a-
lifetime stroke (or TIA) in the oldest age groups [14]. Details of case ascertainment in each of our study locations
have been published elsewhere [5]. In brief, almost all
first-ever stroke patients in these locations of the Autonomous Regions of Spain are admitted to hospital if they
seek medical help. Less than 2% of cases were identified
in the primary care setting (‘cold’ pursuit method) in
Mallorca, Segovia and Talavera (in the Sentinel Medical
Net database) and in the Lugo database. It was not possible to obtain data on nonhospitalized patients from
Almería. However, since it is the only hospital serving the
study area, it is reasonable to assume the rate to be !5%.
In Spain, because of the health care policy and cultural
factors, there is a strong tendency to seek hospital consultation when a stroke or TIA is suspected. This enables
neuroimaging to be performed in the acute phase (emergency room) in almost all patients, and, hence, the timing
of this diagnostic procedure makes it unlikely that TIAs
Stroke Incidence Rate in Spain
Cerebrovasc Dis 2012;34:272–281
Discussion
The present study is the first population-based stroke
incidence study in Spain using current and homogeneous
methodology applied concurrently in several geographical locations. The considerable sample sizes and universal
application of CT in the assessments provide robust estimations of incident TIA as well as stroke and stroke subtypes.
277
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Table 4. Age-standardized (to European population) incidence rates of stroke and subtypes (!100,000 inhabitants/year)
TIA
180
160
Ischemic stroke
1,200
Men
Women
1,000
140
120
800
100
600
80
400
60
40
200
20
0
0
18
25
35
250
45
55
65
75
18
85+
ICH
25
35
45
55
65
75
65
75
85+
SAH
30
25
200
20
150
15
100
10
50
5
0
0
18
25
35
45
55
65
Age (years)
75
85+
18
25
35
45
55
85+
Age (years)
Fig. 2. Crude incidence rates (!100,000 person-years) according to stroke subtype in the IBERICTUS study.
278
Cerebrovasc Dis 2012;34:272–281
stroke-related early death is usually of the hemorrhagic
stroke subtype, we believe that there can be only a few
possible stroke cases that had not been registered. Similar
limitations affect most of the studies addressing the epidemiology of stroke, i.e. the nondetection of stroke patients among the older age groups who die suddenly away
from the administrative monitoring of a hospital.
Incidence
It is difficult to compare data derived from different
studies reliably since they may have been conducted at
Díaz-Guzmán et al.
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and hemorrhagic and ischemic strokes could have been
misclassified. By contrast, a very important study conducted in Oxfordshire in the UK [15] shows a very low
hospitalization rate in stroke patients (56%), and this implies a delay in neuroimaging.
Incidence data from death certificates and autopsy reports for fatal cases are hard to obtain because of legal and
administrative restrictions operating in Spain. This is an
unavoidable limitation of the IBERICTUS study. However, in our study the proportion of hemorrhagic strokes
(15%) was comparable with other studies [16–20]. Since
Subtypes of Stroke
Because CT brain scans were performed early in our
patients, our assignment of ischemic or hemorrhagic
stroke can be made with confidence. A stroke subtype diagnosis (ischemic vs. hemorrhagic) was reached in 99% of
cases. However, determining ischemic stroke subtyping
may be difficult in a multicentered incidence study such as
ours. Our interobserver concordance is only modest using
the modified Lausanne criteria, as we had seen in the pilot
study conducted prior to the start of the current IBERICTUS study [11]. The main interobserver discordance was
with respect to ‘undetermined cause’ (27% of our ischemic
stroke cases). Overall, the proportions of LAA (1/3), CE
(1/5) and ‘lacunar’ stroke or SAO (1/6) are similar to other
studies in Western countries and stroke registries.
Ischemic and hemorrhagic strokes show similar increasing incidence rates with age and higher numbers in
men in all age groups. One exception is SAH, for which
the incidence in women is 1.76-fold (95% CI 1.04–3.01)
that in men. This gender difference begins around 45
years of age and increases thereafter, except for the group
aged 65–74 years. Our overall incidence of SAH (4.2/
100,000 person-years) is similar to that observed in South
and Central America but lower than in other regions [28].
Stroke Incidence Rate in Spain
TIA Incidence
In the IBERICTUS study, 16% of all first strokes were
TIAs. Compared with other developed countries, the
TIA incidence rates in Spain are higher than in Russia
[29] and lower than in the USA [30, 31], England [32], Portugal [33] and Japan [34, 35], but very similar to the 15%
observed in a recent nationwide study in the Netherlands
[36]. TIA follows an identical age trend as that observed
in stroke, with higher rates in men than in women across
all age groups, except for the oldest age group, which is
due, at least in part, to a cohort effect (see above). With
the participation of specialist neurologists in classifying
the events and the almost universal deployment of CT
scanning in the acute phase of the transient neurological
deficit, it is unlikely that events that ‘mimic’ ischemic
brain events, such as structural lesions (i.e. subdural hematomas, tumors), had been erroneously included. In addition, cases of isolated acute dysarthria or dysphagia
were not registered. However, because of the nature of the
study we cannot exclude other nonvascular diagnoses
such as migraine, epilepsy or transient hypoglycemia,
which in some clinical series may account for up to 20%
of cases [37]. Diffusion-weighted magnetic resonance imaging was not employed in the vast majority of the cases.
One limitation of the present study is the nondetection of
very short TIAs since patients suffering these attacks seldom seek medical attention. These patients can be detected in a prevalence study (for example, door-to-door
methodology), but establishing the true incidence is very
complicated.
In-Hospital Mortality
In this phase of our epidemiological study, we were
unable to obtain data on the 28-day mortality rates because of Spanish laws limiting the investigation of deaths
occurring once the patient has been discharged from hospital. Hence, it is difficult to compare in-hospital mortality with 28-day mortality from other studies. However,
in-hospital mortality has been proposed as an indicator
of health care quality, and a rate of 12%, such as observed
in our study, is very acceptable. The case fatality rate in
IBERICTUS was similar for men and women and increased exponentially with age in both genders, reaching
peak values at the age of 85+ years. The geographical distribution shows higher in-hospital mortality rates in the
northern (Lugo) and central provinces (Segovia and Talavera), a lower rate in the Mediterranean region (Mallorca) and lowest rate in southern Spain (Almería). Agestandardized rates of in-hospital mortality were particularly high, and statistically significantly so, in Lugo
Cerebrovasc Dis 2012;34:272–281
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different times and, even, using different inclusion criteria, but compared with other Western countries, the
stroke incidence rates in Spain appear similar to those in
Sweden [21], higher than in the USA [22], England [17],
Germany [18], Poland [23] and France [23, 24], and lower
than in Italy [19], Ukraine [25], Greece [26], Norway [20],
Portugal [27] and Estonia [16] (online suppl. table 1). The
incidence rates increase with age, with higher rates in
men than in women across all age groups. There is a trend
towards attenuation of differences in rates in the older age
groups (185 years of age), probably due to fewer cases
among men (‘true’ lower incidence rate) and a higher proportion of women in the population (ratio of women to
men of 2:1). This disproportion of older women in the
Spanish population is due, at least in part, to the high
death rate amongst men during, and immediately after,
the Spanish Civil War (1936–1939). There are differences
in the incidence of stroke between regions in Spain, with
higher rates in the south and the northwest regions compared to the central and Mediterranean regions. These
differences are in the process of undergoing more detailed analyses. Overall, there appears to be a gradient
related to socioeconomic status and risk factor profile,
and less likely to methodological issues.
compared with the other provinces. These differences are
not attributable to different subtypes of stroke between
the areas but may be due, rather, to the overall health status of the population, as well as to improvements in the
standard of care (e.g. specialized stroke units), or they
may be artefactual due to different rates of hospital discharge (i.e. home or residential care). The methodology
employed in the IBERICTUS study does not support
more profound analyses of these differences in relation to
mortality.
In conclusion, the present study provides de novo and
robust estimates of the incidence of first-ever stroke and
TIA in Spain based on populations from different geographical areas. The data may provide important insights
and perspective into the epidemiology of stroke in Europe.
Acknowledgments
Our thanks go to the Centro de Epidemiología, Investigación
e Información en Salud (CEIIS) for help with the logistics of data
retrieval and verification, to Margarita Alonso-Arroyo (CEIIS)
for help with the statistical analyses and to other contributors in
the different clinical centers (online suppl. appendices). Editorial
assistance was provided by Dr. Peter R. Turner.
Disclosure Statement
This study was sponsored by Sanofi-Aventis via a donation to
the Spanish Neurology Society.
References
280
8 Sudlow CLM, Warlow CP: Comparing stroke
incidence worldwide: what makes studies
comparable? Stroke 1996; 27:550–558.
9 Aho K, Harmsen P, Hatano S, Marquardsen
J, Smirnov VE, Strasser T: Cerebrovascular
disease in the community: results of a WHO
collaborative study. Bull World Health Organ 1980;58:113–130.
10 Castillo V, Bogousslavski J: Early classification of stroke. Cerebrovasc Dis 1997; 7(suppl
3):5–11.
11 Díaz-Guzmán J, Egido-Herrero JA, Fuentes
B, Fernández-Pérez C, Gabriel-Sánchez R,
Barberà G, Abilleira S; Proyecto Ictus del
Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de
Neurología: Incidence of strokes in Spain:
the Iberictus study. Data from the pilot
study. Rev Neurol 2009;48:61–65.
12 Spain demographics. http://www.ine.es (accessed March 2011).
13 European population. http://nui.epp.eurostat.ec.europa.eu/nui/show.do?dataset=
demo_pjan&lang=en (accessed March 2011).
14 Feigin VL, Lawes CMM, Bennett DA, Anderson CS: Stroke epidemiology: a review of
population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2003;2:43–53.
15 Rothwell PM, Coull AJ, Giles MF, Howard
SC, Silver LE, Bull LM, Gutnikov SA, Edwards P, Mant D, Sackley CM, Farmer A,
Sandercock PA, Dennis MS, Warlow CP,
Bamford JM, Anslow P; Oxford Vascular
Study: Change in stroke incidence, mortality, case-fatality, severity, and risk factors in
Oxfordshire, UK from 1981 to 2004 (Oxford
Vascular Study). Lancet 2004; 363: 1925–
1933.
Cerebrovasc Dis 2012;34:272–281
16 Vibo R, Körv J, Haldre S, Roose M: First-year
results of the Third Stroke Registry in Tartu,
Estonia. Cerebrovasc Dis 2004;18:227–231.
17 Wolf CDA, Giroud M, Kolomisky-Rabas P,
Dundas R, Lemesle M, Heuschmann P, Rudd
A: Variations in stroke incidence and survival in 3 areas of Europe. European Registries
of Stroke (EROS) Collaboration. Stroke
2000;31:2074–2079.
18 Kolominsky-Rabas PL, Sarti C, Heuschmann PU, Graf C, Siemonsen S, Neundoerfer B, Katalinic A, Lang E, Gassmann KG,
von Stockert TR: A prospective communitybased study of stroke in Germany – the Erlangen Stroke Project (ESPro). Stroke 1998;
29:2501–2506.
19 Carolei A, Marini C, Di Napoli M, Di
Gianfilippo G, Santalucia P, Baldassarre M,
De Matteis G, di Orio F: High stroke incidence in the prospective community-based
L’Aquila registry (1994–1998). First year’s results. Stroke 1997; 28:2500–2506.
20 Ellekjaer H, Holmen J, Indredavik B, Terent
A: Epidemiology of stroke in Inherred, Norway, 1994 to 1996. Stroke 1997;28:2180–2184.
21 Johansson B, Norrving B, Lindgren A: Increased stroke incidence in Lund-Orup,
Sweden, between 1983 to 1985 and 1993 to
1995. Stroke 2000; 31:481–486.
22 Brown RD, Whisnant JP, Sicks JD, O’Fallon
WM, Wiebers DO: Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989. Stroke 1996;
27:373–380.
23 European Registers of Stroke (EROS) Investigators: Incidence of stroke in Europe at the
beginning of the 21st Century. Stroke 2009;
40:1557–1563.
Díaz-Guzmán et al.
Downloaded by:
Kainan University
203.64.11.45 - 2/3/2015 3:20:43 PM
1 Bonita R, Mendis S, Truelsen T, Bogousslavsky
J, Toole J, Yatsu F: The Global Stroke Initiative. Lancet Neurol 2004;3:391–393.
2 Thorvaldsen P, Asplund K, Kuulasmaa K,
Rajakangas AM, Shroll M: Stroke incidence,
case fatality, and mortality in the WHO
MONICA project. World Health Organization Monitoring Trends and Determinants
in Cardiovascular Disease. Stroke 1995; 26:
361–367.
3 Asplund K, Bonita R, Kuulasmaa K, Rajakangas AM, Schaedlich H, Suzuki K, Thorvaldsen P, Tuomilehto J: Multinational comparisons of stroke epidemiology. Evaluation
of case ascertainment in the WHO MONICA Stroke Study. World Health Organization Monitoring Trends and Determinants
in Cardiovascular Disease. Stroke 1995; 26:
355–360.
4 Medrano Alberto MJ, Boix Martinez R, Cerrato Crespan E, Ramirez Santa-Pau M: Incidence and prevalence of ischaemic heart disease and cerebrovascular disease in Spain: a
systematic review of the literature. Rev Esp
Salud Pública 2006;80:5–15.
5 Díaz-Guzmán J, Egido-Herrero JA, GabrielSánchez R, Barberà G, Fuentes B, FernándezPérez C, Abilleira S; Proyecto Ictus del Grupo
de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología:
Incidence of strokes in Spain. Methodological foundations of the Iberictus Study (in
Spanish). Rev Neurol 2008;47:617–623.
6 Population 2005 census of the Spanish National Institute of Statistics. http://www.ine.
es (accessed March 2011).
7 Malmgren R, Warlow C, Bamford J, Sandercork P: Geographical and secular trends in
stroke incidence. Lancet 1987; 2:1197–1198.
Stroke Incidence Rate in Spain
29 Feigin VL, Shishkin SV, Tzirkin GM, Vinogradova TE, Tarasov AV, Vinogradov SP, Nikitin YP: A population-based study of transient ischemic attack incidence in Novosibirsk, Russia, 1987–1988 and 1996–1997.
Stroke 2000;51:9–13.
30 Edlow JA, Kim S, Pelletier AJ, Camargo CA
Jr: National study on emergency department
visits for transient ischemic attack, 1992–
2001. Acad Emerg Med 2006;13:666–672.
31 Kleindorfer D, Panagos P, Pancioli A,
Khoury J, Kissela B, Woo D, Schneider A, Alwell K, Jauch E, Miller R, Moomaw C, Shukla R, Broderick JP: Incidence and short-term
prognosis of transient ischemic attack in a
population-based study. Stroke 2005; 36:
720–723.
32 Rothwell PM, Warlow CP: Timing of TIAs
preceding stroke: time window for prevention is very short. Neurology 2005; 64: 817–
820.
33 Correia M, Silva MR, Magalhaes R, Guimaraes L, Silva MC: Transient ischemic attacks
in rural and urban northern Portugal: incidence and short-term prognosis. Stroke
2006;37:50–55.
34 Ueda K, Kiyohara Y, Hasuo Y, Yanai T,
Kawano H, Wada J, Kato I, Kajiwara E, Omae
T, Fujishima M: Transient cerebral ischemic
attacks in a Japanese community, Hiyasama,
Japan. Stroke 1987; 18:844–848.
35 Urakami K, Igo M, Takahashi K: An epidemiologic study of cerebrovascular disease
in Western Japan: with special reference to
transient ischemic attacks. Stroke 1987; 18:
396–401.
36 Vaartjes I, Reitsma JB, de Bruin A, Bergervan Sijl M, Bos MJ, Breteler MM, Grobbee
DE, Bots ML: Nationwide incidence of first
stroke and TIA in the Netherlands. Eur J
Neurol 2008;15:1315–1323.
37 Amort M, Fluri F, Schäfer J, Weisskopf F,
Katan M, Burow A, Bucher HC, Bonati LH,
Lyrer PA, Engelter ST: Transient ischemic
attack versus transient ischemic attack mimics: frequency, clinical characteristics and
outcome. Cerebrovasc Dis 2011;32:57–64.
Cerebrovasc Dis 2012;34:272–281
281
Downloaded by:
Kainan University
203.64.11.45 - 2/3/2015 3:20:43 PM
24 Béjot Y, Rouaud O, Jacquin A, Osseby GV,
Durier J, Manckoundia P, Pfitzenmeyer P,
Moreau T, Giroud M: Stroke in the very old:
incidence, risk factors, clinical features, outcomes and access to resources – a 22-year
population-based study. Cerebrovasc Dis
2010;29:111–21
25 Mihalka L, Smolanka V, Bulecza B, Mulesa
S, Bereczki D: A population study of stroke
in West-Ukraine. Stroke 2001;32:2227–2231.
26 Vemmos KN, Bots ML, Tsibouris PK, et al:
Stroke incidence and case-fatality in Southern Greece. Stroke 1999; 30:36–70.
27 Correia M, Silva MR, Matos I, Magalhaes R,
Castro J, Ferro JM: Prospective communitybased study of stroke in Northern Portugal.
Incidence and case fatality in rural and urban populations. Stroke 2004;35:2048–2053.
28 de Rooij NK, Linn FHH, van der Plas JA, Algra A, Rinkel GJE: Incidence of subarachnoid haemorrhage: a systematic review with
emphasis on region, age, gender and time
trends. J Neurol Neurosurg Psychiatry 2007;
78:1365–1372.