Research

JAMA Neurology | Original Investigation

Worldwide Incidence of Aneurysmal Subarachnoid

Hemorrhage According to Region, Time Period, Blood
Pressure, and Smoking Prevalence in the Population
A Systematic Review and Meta-analysis
Nima Etminan, MD; Han-Sol Chang, MD; Katharina Hackenberg, MD; Nicolien K. de Rooij, MD, PhD;
Mervyn D. I. Vergouwen, MD, PhD; Gabriel J. E. Rinkel, MD, FRCPE; Ale Algra, MD, PhD

Supplemental content
IMPORTANCE Subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms is a
subset of stroke with high fatality and morbidity. Better understanding of a change in
incidence over time and of factors associated with this change could facilitate primary
prevention.

OBJECTIVE To assess worldwide SAH incidence according to region, age, sex, time period,
blood pressure, and smoking prevalence.

DATA SOURCES We searched PubMed, Web of Science, and Embase for studies on SAH
incidence published between January 1960 and March 2017. Worldwide blood pressure and
smoking prevalence data were extracted from the Noncommunicable Disease Risk Factor and
Global Burden of Disease data sets.

STUDY SELECTION Population-based studies with prospective designs representative of the

entire study population according to predefined criteria.

DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data according to
PRISMA guidelines. Incidence of SAH was calculated per 100 000 person-years, and risk
ratios (RRs) including 95% CIs were calculated with multivariable random-effects binomial
regression. The association of SAH incidence with blood pressure and smoking prevalence
was assessed with linear regression.

MAIN OUTCOMES AND MEASURES Incidence of SAH.

Author Affiliations: Department of

RESULTS A total of 75 studies from 32 countries were included. These studies comprised 8176
Neurosurgery, Mannheim University
patients with SAH were studied over 67 746 051 person-years. Overall crude SAH incidence Hospital, Medical Faculty Mannheim,
across all midyears was 7.9 (95% CI, 6.9-9.0) per 100 000 person-years; the RR for women Heidelberg University, Mannheim,
was 1.3 (95% CI, 0.98-1.7). Compared with men aged 45 to 54 years, the RR in Japanese Germany (Etminan, Chang,
Hackenberg); Department of
women older than 75 years was 2.5 (95% CI, 1.8-3.4) and in European women older than 75 Rehabilitation, St Antonius Hospital,
years was 1.5 (95% CI, 0.9-2.5). Global SAH incidence declined from 10.2 (95% CI, 8.4-12.5) Nieuwegein, the Netherlands
per 100 000 person-years in 1980 to 6.1 (95% CI, 4.9-7.5) in 2010 or by 1.7% (95% CI, (de Rooij); Brain Centre Rudolf
Magnus, Department of Neurology
0.6-2.8) annually between 1955 and 2014. Incidence of SAH declined between 1980 and
and Neurosurgery, University Medical
2010 by 40.6% in Europe, 46.2% in Asia, and 14.0% in North America and increased by 59.1% Centre Utrecht, Utrecht University,
in Japan. The global SAH incidence declined with every millimeter of mercury decrease in Utrecht, the Netherlands
systolic blood pressure by 7.1% (95% CI, 5.8-8.4) and with every percentage decrease in (Vergouwen, Rinkel, Algra); Julius
Center for Health Sciences and
smoking prevalence by 2.4% (95% CI, 1.6-3.3). Primary Care, University Medical
Centre Utrecht, Utrecht University,
CONCLUSIONS AND RELEVANCE Worldwide SAH incidence and its decline show large regional Utrecht, the Netherlands (Algra).
differences and parallel the decrease in blood pressure and smoking prevalence. Corresponding Author: Nima
Understanding determinants for regional differences and further reducing blood pressure Etminan, MD, Department of
Neurosurgery, Mannheim University
and smoking prevalence may yield a diminished SAH burden. Hospital, Medical Faculty Mannheim,
Heidelberg University,
Theodor-Kutzer-Ufer 1-3, 68135
JAMA Neurol. doi:10.1001/jamaneurol.2019.0006 Mannheim, Germany (nima.etminan
Published online January 19, 2019. @medma.uni-heidelberg.de).

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 Research Original Investigation
S
ubarachnoid hemorrhage (SAH) from a ruptured intra-
cranial aneurysm accounts for 5% of all strokes and car-
ries an exceptionally high disease-specific burden; half
of patients with SAH are younger than 55 years, one-third die
within the initial days to weeks after the hemorrhage, and most
survivors have long-term disability or cognitive impairment.1
On a community level, the loss of productive life-years after
SAH is similar in magnitude to that of ischemic stroke. The
crude incidence of SAH was previously estimated to be 9 per
100 000 person-years but varied considerably according to geo-
graphic location, age, and sex.2 More recently, register-based
or regional studies have reported conflicting data on reduc-
tion of SAH incidence over time.3,4 If SAH incidence has in-
deed declined and potential determinants for such a decline
could be detected on a population-based level, then this would
have important implications for primary prevention strate-
gies and thus reduction of the burden of disease in patients with
SAH. We aimed to investigate worldwide and age-specific and
sex-specific incidences of SAH according to region, age, sex,
time period, blood pressure, and smoking prevalence in the
population.5,6
Methods
Search Strategy and Selection Criteria
To identify population-based studies on the incidence of SAH
published between January 1960 and March 2017, we per-
formed a systematic review of PubMed, Web of Science, and
Embase using the keywords “subarachnoid hemorrhage” or
“subarachnoid haemorrhage” and “incidence,” “epidemiol-
ogy,” or “population,” building on our previous studies.2,7 In
addition, we cross-referenced the list of studies with the per-
sonal database of references of one of the authors (G.J.E.R.)
to include missing studies. Our study followed the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines. Inclusion criteria were (1) a prospective
study design, (2) the study population being representative of
the studied population in general, (3) SAH reported as an in-
dividual entity, (4) the data including crude figures or en-
abling crude calculation of SAH incidence, (5) case findings
permitting inclusion of all hospitals in the region and either
involvement of general practitioners or review of death cer-
tificates by the study investigator(s), (6) diagnostic verifica-
tion, including a neuroimaging rate greater than 80% or at least
lumbar puncture or autopsy, (7) an upper age limit for the study
not lower than 75 years, and (8) a lower age limit not greater
than 25 years. Registry-based, hospital-based, and cohort stud-
ies, studies on nonaneurysmal SAH, and studies reporting data
only for specific ethnic groups were excluded. In studies re-
porting on similar study populations or study periods, we only
included the most recent study or the study with the greater
amount of person-years or more sophisticated case finding
methods.
Data Extraction
For studies published between October 2005 and March 2017,
2 reviewers (H.-S.C. and K.H.) assessed all newly retrieved stud-
E2 JAMA Neurology Published online January 19, 2019 (Reprinted)
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Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage
Key Points
Question What are the time trends and associated factors for the
incidence of aneurysmal subarachnoid hemorrhage (SAH)?
Findings In this systematic review and meta-analysis including
75 studies and 8176 patients, the crude global incidence of SAH
declined from 10.2 per 100 000 person-years in 1980 to 6.1 in
2010, but large variation according to region, age, and sex exists.
The global incidence of SAH decreased by 7.1% with every
millimeter of mercury decrease in systolic blood pressure,
11.5% for every millimeter of mercury decrease in diastolic blood
pressure, and 2.4% for every percentage decrease in smoking
prevalence.
Meaning Understanding determinants for regional differences
and further reducing blood pressure and smoking prevalence may
yield a diminished SAH burden.
ies independent from each other and registered the following
items in a data extraction form: (1) size of study population;
(2) study region; (3) midyear and study period; (4) number of
patients with SAH; (5) case finding methods for SAH; (6) di-
agnostic criteria for SAH; and (7) age-specific and sex-specific
incidence. For previously identified studies, we used data we
had extracted in the same fashion.2,7 Excellent diagnostics was
defined as greater than 90% of patients with SAH being diag-
nosed with brain imaging (computed tomography [CT] or mag-
netic resonance imaging). In the event of disagreement on
extracted data, the article was assessed by 2 other authors (N.E.
and M.D.I.V.) independently from each other and discussed be-
tween the 4 authors until agreement was achieved. We used
incidence rates relating to the entire population, without ad-
justment for age or sex. To determine the association of SAH
incidence with age and sex, we collected age-specific and sex-
specific incidence from the subset of studies that provided suf-
ficient data. Study investigators were contacted for missing data
on crude incidence of SAH when required. Since only 14% of
studies included in our meta-analysis reported data on smok-
ing or hypertension prevalence in patients with SAH and not
for the entire reported population, we extracted age-specific,
sex-specific, midyear-specific, and country-specific systolic and
diastolic blood pressure values from the Noncommunicable
Disease Risk Factor (NCD) data set5 and smoking prevalence
data from the Global Burden of Disease Study6 to analyze their
association with SAH incidence within the age-specific and sex-
specific SAH incidence data set.
Data Analyses
For each of the included studies, the crude SAH incidence with
corresponding 95% CIs was calculated with Poisson meth-
ods. For all subsequent analyses, we used random-effects bi-
nomial regression, with the number of SAHs and the number
of person-years for each study as variables (RMA.GLMN
module in R version 3.4.3 [The R Foundation]). Overall and
regional incidences were estimated based on the models’ in-
tercept; in addition, I2 was calculated as a measure of varia-
tion, ie, heterogeneity, between the included studies.8 We
considered an I2 of 25% to 49% as low, 50% to 74% as moder-
ate, and 75% or greater as high heterogeneity. To assess
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 Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage
regional differences, we compared studies by continent or
country. Next, we determined the association of age, sex, and
time period with the incidence of SAH. In addition, we stud-
ied regional patterns of the association of age, sex, and time
period with SAH incidence. To estimate current SAH inci-
dence vs previous SAH incidence, we used the regression
models and midyear cut-off of all studies (1996) within 15 years,
which, after rounding, corresponded to 2010 (current SAH in-
cidence) and 1980 (historic SAH incidence). In the age-
specific and sex-specific data subset, we adjusted the time trend
analyses for age and sex. In addition, we determined the
association of blood pressure and smoking prevalence with SAH
incidence. To describe patterns of blood pressure and smok-
ing prevalence over time, we used linear regression analysis.
Multivariable regression was used to estimate the (indepen-
dent) contribution of continent, age, and sex as well as time
trends to SAH incidence. Since our previous meta-analysis
found a higher SAH incidence in Finland and Japan com-
pared with the reference population,2 we specifically ana-
lyzed the SAH incidence according to time for these coun-
tries. Included studies were reviewed for adherence to core
and/or supplemental criteria for population-based stroke stud-
ies in relation to the midyear cutoff of all studies (1996).9 In
sensitivity analyses, we restricted the time trend analysis to
studies with at least 90% cranial scanning as well as studies
with a midyear of study of 1985 at the earliest and with data
on percentage of CT scanning.
Results
Data from 75 population-based studies and 84 study periods
were included (eFigure 1 in the Supplement). For all 75 stud-
ies (range of midyears, 1955-2014), 55 (73%) fulfilled core
criteria for population-based studies. For the 56 studies pub-
lished after 1996, 48 studies (86%) fulfilled these criteria.
These studies described 8176 patients with SAH over
67 746 051 person-years from 32 countries and 6 continents.
The median percentage of cranial imaging for detection of
SAH was 91% (interquartile range, 78-97). Incidences of SAH
by region, population size, study midyear, and case finding
method as well as the diagnostic criteria for each study are
listed in eTable 1 in the Supplement. Summary characteris-
tics of the overall and age-specific and sex-specific data sets
are provided in eTable 2 in the Supplement. Overall crude
SAH incidence across all midyears was 7.9 (95% CI, 6.9-9.0)
per 100 000 person-years (I 2 = 96.6%) (Figure 1 10-51 and
Figure 252-85).
SAH Incidence by Region and Time Trends
The crude worldwide SAH incidence (84 study periods) was
6.1 (95% CI, 4.9-7.5) per 100 000 person-years for 2010 and 10.2
(95% CI, 8.4-12.5) for 1980 and declined annually by 1.7% (95%
CI, 0.6-2.8) between 1955 and 2014. Figure 1 and Figure 2 dis-
play the crude SAH incidences by continent and region. The
SAH incidence for 2010 in Europe (45 study periods) was es-
timated to be 6.3 (95% CI, 4.9-8.1) per 100 000 person-years
and declined annually by 1.7% (95% CI, 0.4-3.1) since 1972.10-51
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Original Investigation Research
For Finland (5 study periods), the SAH incidence was 16.6 (95%
CI, 13.4-20.5) per 100 000 person-years, with no clear change
over time (1972-1990); after 1990, no new studies fulfilling our
inclusion criteria appeared. For Asia (13 study periods), the SAH
incidence for 2010 was estimated to be 7.7 (95% CI, 2.8-21.7)
per 100 000 person-years, and the annual decline was 2.0%
(95% CI, −3.9 to 7.9) since 1977.52-63 Since 7 of 13 study peri-
ods from Asia were from Japan alone and there was a large
heterogeneity between Japan and the remainder of Asia, data
for Japan are presented separately. The SAH incidence in Ja-
pan was estimated to be 28.0 (95% CI, 25.3-31.0) per 100 000
person-years and increased annually by 1.6% (95% CI, 0.8-
2.3) since 1977.52-57 In Asia excluding Japan, the SAH inci-
dence for 2010 was estimated to be 3.7 (95% CI, 0.1-13.3) per
100 000 person-years, and the annual decline since 1984 was
1.3% (95% CI, −7.2 to 9.8).58-63 For North America (7 study pe-
riods), the SAH incidence for 2010 was estimated to be 6.9 (95%
CI, 4.8-10.0) per 100 000 person-years, and the annual de-
cline was 0.7% (95% CI, −0.4 to 1.8) since 1955.73-76 Crude in-
cidences for SAH, risk ratios (RRs) for SAH incidence, and time
trends for all geographical locations, including Middle and
South America (8 study periods),77-84 Australia and New Zea-
land (10 study periods),64-72 and Africa (Nigeria),85 are sum-
marized in Table 1. Continental and regional SAH incidences
and time trends from studies reporting incidence data in the
same population over several time periods are highlighted in
eFigure 2 in the Supplement. In this subset of studies, there
was a decrease in SAH incidence in most studies from
Europe11,13,15,40,47,48,50,51 and the study from North America74
and an increase in SAH incidence in the 2 studies from
Japan.53,86
The sensitivity analysis for the overall decline in
the 40 studies that had at least 90% CT sc an-
ning 14,18,20-24,27-30,32,34,35,37,39,44,49,51,53,54,56-59,62,66,68,69,71,72,75-82,84
demonstrated an annual decrease in SAH incidence of 2.1%
(95% CI, −1.0 to 5.0). The 63 studies with a midyear of study
after 1985 and data on percentage of CT
scanning10,13-15,18-25,27-35,37-39,42-45,48-51,53-60,62-69,71-73,75-84
showed an annual decrease in SAH incidence of 1.4% (95% CI,
−1.0 to 3.7) and an annual decrease in SAH incidence after ad-
justment for percentage of CT scanning of 1.3% (95% CI, −1.2
to 3.8).
SAH Incidence Stratified by Age, Sex, Region,
and Time Trends
T w e n t y- n i n e
studies10,19,20,27-29,32,34,36,43,51-53,57,58,64,66,67,72,73,77-79,83-88 with
data on 34 study periods reported age-specific and sex-
specific SAH incidence for 2133 patients with SAH over
17 029 016 person-years in 18 countries and 6 continents
(eTable 2 in the Supplement). In this subset of studies, the over-
all incidence was 10.3 (95% CI, 9.0-11.9). Irrespective of geo-
graphical location, the incidence of SAH increased with in-
creasing age but increased distinctly more in women older than
55 years (eFigure 3 and eTables 3 and 4 in the Supplement).
The increase of SAH incidence associated with increasing age
was higher in Japanese women older than 75 years (RR, 2.5;
95% CI, 1.8-3.4) than in European women older than 75 years
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 Research Original Investigation Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage

Figure 1. Crude Subarachnoid Hemorrhage (SAH) Incidence by Country and Midyear in Europe

Study No. of SAH Incidence

Country Source Midyear SAHs Patient-Years (95% CI)
Europe
Croatia Pikija et al,10 2012 2008 30 368 230 8.2 (5.7-11.7)
Denmark Hansen and Marquardsen,11 1977 1972 13 197 542 6.6 (3.8-11.3)
Denmark Truelsen et al,12 2002 1984 49 315 168 15.6 (11.8-20.6)
Denmark Jørgensen et al,13 1992 1990 2 85 611 2.3 (0.6-9.3)
Estonia Vibo et al,14 2005 2002 18 202 244 8.9 (5.6-14.1)
Finland Numminen et al,15 1996 1972 42 226 200 18.6 (13.7-25.1)
Finland Sivenius et al,16 1985 1979 24 159 033 15.1 (10.1-22.5)
Finland Numminen et al,15 1996 1979 33 273 700 12.1 (8.6-17.0)
Finland Sarti et al,17 1991 1984 407 1 890 000 21.5 (19.5-23.7)
Finland Numminen et al,15 1996 1990 39 269 608 14.5 (10.6-19.8)
France Biotti et al,18 2010 1995 86 3 303 036 2.6 (2.1-3.2)
Georgia Tsiskaridze et al,19 2004 2002 23 140 940 16.3 (10.8-24.6)
Germany Kolominsky-Rabas et al,20 1998 1995 12 202 900 5.9 (3.4-10.4)
Germany Palm et al,21 2010 2006 17 335 812 5.1 (3.2-8.1)
Greece Stranjalis et al,22 2014 2010 5 86 436 5.8 (2.4-13.9)
Iceland Hilmarsson et al,23 2013 2008 23 238 984 9.6 (6.4-14.5)
Ireland Kelly et al,24 2012 2006 26 294 529 8.8 (6.0-13.0)
Italy Ricci et al,25 1991 1988 15 147 654 10.2 (6.1-16.9)
Italy D'Alessandro et al,26 1992 1989 6 114 325 5.3 (2.4-11.7)
Italy Lauria et al,27 1995 1992 12 211 389 5.7 (3.2-10.0)
Italy Sacco et al,28 2009 1996 118 1 488 225 7.9 (6.6-9.5)
Italy Di Carlo et al,29 2003 1996 12 179 186 6.7 (3.8-11.8)
Italy D'Alessandro et al,30 2000 1997 14 118 723 11.8 (7.0-19.9)
Italy Musolino et al,31 2005 2000 1 40 293 2.5 (0.4-17.6)
Italy Manobianca et al,32 2010 2001 3 77 470 3.9 (1.3-12.0)
Italy Corso et al, 200933 and 201334 2006 44 625 515 7.0 (5.2-9.5)
Italy Janes et al,35 2013 2008 25 306 624 8.2 (5.5-12.1)
Netherlands Herman et al,36 1982 1979 24 302 712 7.9 (5.3-11.8)
Portugal Correia et al,37 2013 1999 6 74 178 8.1 (3.6-18.0)
Portugal Correia et al,37 2013 1999 17 172 046 9.9 (6.1-15.9)
Spain Caicoya et al,38 1996 1991 28 417 033 6.7 (4.6-9.7)
Spain Díaz-Guzmán et al,39 2012 2006 59 1 440 979 4.1 (3.2-5.3)
Sweden Terént,40 1988 1977 13 96 690 13.5 (7.8-23.2)
Sweden Norrving and Löwenhielm,41 1988 1984 28 474 777 5.9 (4.1-8.5)
Sweden Terént,40 1988 1985 10 92 208 10.9 (5.8-20.2)
Sweden Stegmayr et al,42 2004 1993 1547 8 212 800 18.8 (17.9-19.8)
Sweden Khan et al,43 2012 1995 197 2 674 144 7.4 (6.4-8.5)
Sweden Nilsson et al,44 2000 1996 106 1 141 752 9.3 (7.7-11.2)
Sweden Appelros et al,45 2002 1999 11 123 503 8.9 (4.9-16.1)
Sweden Hallström et al,46 2008 2001 17 234 505 7.3 (4.5-11.7)
United Kingdom Bamford et al,47 1990 1984 33 420 000 7.9 (5.6-11.1)
United Kingdom Wolfe et al,48 2002 1996 77 938 132 8.2 (6.6-10.3)
United Kingdom Syme et al,49 2005 1999 23 212 708 10.8 (7.2-16.3)
United Kingdom Heuschmann et al,50 2008 2001 94 1 780 038 5.3 (4.3-6.5)
United Kingdom Lovelock et al,51 2010 2005 38 546 636 7.0 (5.1-9.6)
Total: I2 = 91.7% 3427 31 254 218 8.3 (7.2-9.5)

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Incidence of SAH per 100 000 Patient-Years (95% CI)

Crude SAH incidence per 100 000 person-years with 95% CIs are presented according to country and midyear in Europe.

(RR, 1.5; 95% CI, 0.9-2.5) compared with men aged 45 to 54
years from the same region.
The overall sex-specific incidence of SAH was 11.5 (95%
CI, 9.5-13.9) per 100 000 person-years in women vs 9.3 (95%
CI, 7.7-11.3) in men; the RR for women was 1.3 (95% CI, 0.98-
1.7), which remained essentially the same after adjustment for
midyear of study. In Europe, the SAH incidence was 12.5 (95%
CI, 10.1-15.4) per 100 000 person-years in women and 10.7 (95%
CI, 8.2-13.9) in men; the RR for women was 1.1 (95% CI, 0.8-
1.5). In Japan, the incidence in women was 22.9 (95% CI, 15.7-
33.5) per 100 000 person-years and in men was 19.5 (95% CI,
14.2-26.8); the RR for women was 1.3 (95% CI, 0.8-2.1). In Asia
overall, the SAH incidence in women was 17.8 (95% CI, 12.4-
25.7) per 100 000 person-years and in men was 14.8 (95% CI,
10.8-20.3); the RR for women was 1.3 (95% CI, 0.8-2.1) (eTable 4
in the Supplement). The annual decline in overall SAH inci-

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 Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage Original Investigation Research

Figure 2. Crude Subarachnoid Hemorrhage (SAH) Incidence by Continent, Country, and Midyear

Study No. of SAH Incidence

Country Source Midyear SAHs Patient-Years (95% CI)
Asia
Japan Tanaka et al,52 1981 1977 31 225 564 13.7 (9.7-19.5)
Japan Inagawa et al,53 2001 1985 170 807 490 21.1 (18.1-24.5)
Japan Ohkuma et al,54 2002 1993 201 899 910 22.3 (19.5-25.7)
Japan Inagawa et al,53 2001 1995 188 763 686 24.6 (21.3-28.4)
Japan Turin et al,55 2012 1996 190 887 216 21.4 (18.6-24.7)
Japan Hamada et al,56 2004 1998 2115 9 300 000 22.7 (21.8-23.7)
Japan Omama et al,57 2013 2006 328 1 176 400 27.9 (25.0-31.1)
China Zhang et al,58 2013 2010 226 3 652 384 6.2 (5.4-7.1)
Iran Azarpazhooh et al,59 2010 2007 15 450 229 3.3 (2.0-5.5)
India Dalal et al,60 2008 2005 14 313 722 4.5 (2.6-7.5)
Israel Epstein et al,61 1989 1984 85 600 000 14.2 (11.5-17.5)
Kuwait Abdul-Ghaffar et al,62 1997 1992 4 873 597 0.5 (0.2-1.2)
Russia Feigin et al,63 1995 1992 14 158 234 8.9 (5.2-14.9)
Total: I2 = 99.5% 3581 20 108 432 10.4 (5.9-18.5)
Australia and New Zealand
Australia Anderson et al,64 1993 1990 18 208 062 8.7 (5.5-13.7)
Australia Islam et al,65 2008 1995 5 136 095 3.7 (1.5-8.8)
Australia Thrift et al,66 2001 1996 12 133 816 9.0 (5.1-15.8)
Australia Thrift et al,67 2009 1998 56 613 262 9.1 (7.0-11.9)
Australia Islam et al,65 2008 2000 12 143 417 8.4 (4.8-14.7)
Australia Leyden et al,68 2013 2010 7 148 028 4.7 (2.3-9.9)
Australia Newbury et al,69 2017 2010 5 192 072 2.6 (1.1-6.3)
New Zealand Bonita and Thomson,70 1985 1982 148 1 658 908 8.9 (7.6-10.5)
New Zealand Truelsen et al,71 1998 1992 163 18 90 738 8.6 (7.4-10.1)
New Zealand Feigin et al,72 2006 2002 87 897 882 9.7 (7.9-12.0)
Total: I2 = 0% 513 6 022 280 8.5 (7.8-9.3)
North America
Mexico Cantu-Brito et al,73 2010 2008 20 247 665 8.1 (5.2-12.5)
United States Brown et al,74 1996 1955 29 331 081 8.8 (6.1-12.6)
United States Brown et al,74 1996 1965 52 451 611 11.5 (8.8-15.1)
United States Brown et al,74 1996 1975 61 543 561 11.2 (8.7-14.4)
United States Brown et al,74 1996 1985 43 617 554 7.0 (5.2-9.4)
United States Longstreth et al,75 1993 1988 171 2 800 000 6.1 (5.3-7.1)
United States Labovitz et al,76 2006 1995 53 571 700 9.3 (7.1-12.1)
Total: I2 = 68.9% 429 5 563 172 8.5 (7.1-10.2)
South America and Central America
Argentina Bahit et al,77 2016 2014 17 261 180 6.5 (4.1-10.5)
Brazil Minelli et al,78 2007 2004 1 75 053 1.3 (0.2-9.5)
Brazil Cabral et al,79 2009 2005 55 974 094 5.7 (4.3-7.4)
Brazil Cabral et al,80 2016 2012 52 1 073 318 4.8 (3.7-6.4)
Caribbean Smadja et al,81 2001 1998 20 360 000 5.6 (3.6-8.6)
Caribbean Wolfe et al,82 2006 2002 13 478 136 2.7 (1.6-4.7)
Chile Alvarez et al,83 2010 2001 33 688 824 4.8 (3.4-6.7)
Chile Lavados et al,84 2005 2001 15 396 311 3.8 (2.3-6.3)
Total: I2 = 7.4% 206 4 306 916 4.8 (4.1-5.6)
Africa
Nigeria Okon et al,85 2015 2011 20 491 033 4.1 (2.6-6.3)
Overall (All Continents, Including Europe) Total: I2 = 96.6% 8176 67 746 051 7.9 (6.9-9.0)

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Incidence of SAH per 100 000 Patient-Years (95% CI)

Crude SAH incidence per 100 000 person-years with 95% CIs are presented according to continent, country, and midyear. I2 values are calculated per continent and
overall including Europe (Figure 1).

dence was 2.2% (95% CI, 0.7-3.7) in the sex-adjusted analysis
and 2.3% (95% CI, 1.2-3.3) in the age-adjusted analysis (eTable 5
in the Supplement). This decline was more apparent in men
(3.4%; 95% CI, 1.9-4.8) than women (1.3%; 95% CI, −0.3 to 2.8).
After adjustment for age, SAH incidence in Europe tended to
decline (annual decline, 0.7%; 95% CI, −1.3 to 2.7); this ten-
dency was more visible in men. In Japan, there was an
increase in crude SAH incidence (annual increase, 4.3%; 95%
CI, 1.3-7.3) and sex-adjusted SAH incidence (annual increase,
4.2%; 95% CI, 1.3-7.2), which was no longer statistically

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 Research Original Investigation Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage

Table 1. Subarachnoid Hemorrhage (SAH) Incidence, Risk Ratios (RRs), Midyear Range, and Time Trends by Region

Time Trends
No. of RR of Overall SAH Incidence (95% CI)
Geographic Study Overall SAH Incidence (95% Range of Annual Change, %
Location Periods Incidence (95% CI) I2, % CI) Midyears 1980 2010 (95% CI)
Global 84 7.9 (6.9 to 9.0) 96.6 NA 1955-2014 10.2 (8.4 to 12.5) 6.1 (4.9 to 7.5) −1.7
(−2.8 to −0.6)
Europe overall 45 8.3 (7.2 to 9.5) 91.7 1 [Reference] 1972-2010 10.6 (8.5 to 13.3) 6.3 (4.9 to 8.1) −1.7
(−3.1 to −0.4)
Europe without 40 7.5 (6.6 to 8.6) 87.6 1 [Reference]a 1972-2010 8.4 (6.4 to 11.1) 6.9 (5.4 to 8.8) −0.7
Finland (−2.2 to 0.8)
Finland 5 16.6 (13.4 to 20.5)b 65.8 2.1 (1.5 to 3.1)a 1972-1990 16.6 (13.4 to 20.6) ND −0.1
(−3.5 to 3.5)
Asia overall 13 10.4 (5.9 to 18.6) 99.5 1.4 (1.0 to 1.9) 1977-2010 14.3 (4.9 to 41.5) 7.7 (2.8 to 21.7) −2.0
(−7.9 to 3.9)
Asia without 6 4.3 (0.5 to 36.4) 95.5 0.6 (0.4 to 0.9) 1984-2010 5.5 (0.9 to 32.2) 3.7 (0.1 to 13.3) −1.3
Japan (−9.8 to 7.2)
Japan 7 22.5 (20.3 to 24.9) 78.5 2.6 (1.8 to 3.9) 1977-2006 17.6 (15.4 to 20.1) 28.0 (25.3 to 31.0) 1.6
(0.8 to 2.3)
Australia/New 10 8.5 (7.8 to 9.3) 0 0.9 (0.7 to 0.9) 1982-2010 9.4 (0.8 to 11.0) 7.4 (6.0 to 9.2) −0.8
Zealand (−1.8 to 0.3)
North America 7 8.5 (7.1 to 10.2) 68.9 0.7 (0.6 to 0.8) 1955-2008 8.0 (7.2 to 10.1) 6.9 (4.8 to 10.0) −0.7
(−1.8 to 0.4)
South/Middle 8 4.8 (4.1 to 5.6) 7.4 0.5 (0.4 to 0.8) 1998-2014 3.3 (1.6 to 7.1) 5.1 (4.2 to 6.1) 1.4
America (−1.5 to 4.3)
Africa 1 4.1 (2.6 to 6.3) NA 0.5 (0.2 to 1.5) 2011 NA NA NA
Abbreviations: NA, not applicable; ND, no data. Finland is used as the reference value.
a b
Europe without Finland; the RR for Finland is in comparison with this The overall Finnish SAH incidence is derived from incidence studies with a
reference. For the remainder of the comparison, Europe as a whole including midyear range from 1972 to 1990.

Table 2. Association of Mean Blood Pressure (BP) and Smoking Prevalence Time Trends With Subarachnoid Hemorrhage (SAH) Incidencea
Annual Decrease in SAH
Annual Change, % Incidence per Unit
Measure Mean (Range) (95% CI) 1980 Estimate (Range) 2010 Estimate (Range) Decrease, % (95% CI)
Systolic BP, mm Hg 134.9 (106.4 to 161.8) −0.2 (−0.3 to −0.1) 120.4 (118.6 to 122.2) 114.6 (112.9 to 116.3) 7.1 (5.8 to 8.4)
Diastolic BP, mm Hg 79.1 (65.1 to 88.1) 0.01 (−0.02 to 0.04) 70.6 (69.5 to 71.6) 70.8 (69.8 to 71.7) 11.5 (8.8 to 14.3)
Smoking prevalence, % 19.3 (0.3 to 72.9) −0.5 (−0.6 to −0.4) 26.5 (22.7 to 30.3) 11.9 (8.4. to 15.4) 2.4 (1.6 to 3.3)
a
All analyses are adjusted for age and sex.

significant after adjustment for age (annual increase, 0.9%; 95%
CI, −0.6 to 2.4).
Association of Blood Pressure Levels and Smoking
Prevalence With SAH Incidence by Region and Time Trends
Data on systolic and diastolic blood pressures were available
for 18 countries and 34 study periods for which age-specific,
sex-specific, midyear-specific, and country-specific SAH inci-
dence data were available. Mean systolic and diastolic blood
pressures, smoking prevalence, annual changes, and 1980
and 2010 estimates are given in Table 2. The annual changes
in systolic and diastolic blood pressure by age category and
sex between 1980 and 2010 are given in eTable 6 in the
Supplement.
With every millimeter of mercury decrease in systolic blood
pressure, the overall age-adjusted and sex-adjusted inci-
dence of SAH declined by 7.1% (95% CI, 5.8-8.4) (Table 2)
(Figure 3A). With every millimeter of mercury decrease in
diastolic blood pressure, the overall age-adjusted and sex-
adjusted incidence of SAH declined by 11.5% (95% CI, 8.8-
14.3). With every percentage decrease in smoking preva-
lence, the overall age-adjusted and sex-adjusted incidence of
SAH decreased by 2.4% (95% CI, 1.6-3.3) (Figure 3B). The lim-
ited number of data points for individual countries did not per-
mit robust analyses on the association of blood pressure and
smoking prevalence with SAH incidence by country, age, sex,
and time period.
Discussion
The crude global incidence of SAH has declined by 40%
between 1980 and 2010, but there is large variation of SAH in-
cidence according to age, sex, region, time period, blood pres-
sure, and smoking prevalence. Between 1980 and 2010, SAH
incidence declined by 40.6% in Europe, 46.2% in Asia, and
14.0% in North America. The global decrease in SAH inci-
dence paralleled a global decrease in mean blood pressure and
smoking prevalence. In Japan, the SAH incidence increased by
59.1% over the last 3 decades. The higher SAH incidence in
women older than 55 years was striking in Japan and no lon-
ger statistically significant in Europe after adjustment.
A 2014 meta-analysis on worldwide stroke incidence in-
cluding 56 population-based studies89—to our knowledge,
the most recent—did not detect a decrease in crude SAH
incidence between 1980 and 2008. However, the overall

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 Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage Original Investigation Research

clined in Finland. Nevertheless, the estimated incidence from

Figure 3. Association of Time Trends of Blood Pressure and Smoking
Prevalence With Subarachnoid Hemorrhage (SAH) Incidence
this registry study is still higher than the current SAH inci-
dence in other European countries in our data.
A Incidence of SAH by systolic blood pressure There are several potential explanations for our findings
30 140 of a decline in global SAH incidence over the last decades. First,
Time trend of SAH incidence
Incidence of SAH per 100 000 Person-Years

Mean systolic blood pressure level the global SAH incidence may have declined because of a par-
25 allel decline in blood pressure and smoking prevalence in the

Systolic Blood Pressure, mm Hg

130
underlying populations. Because of the nature of our study,
20
we cannot draw causal conclusions, but it is highly likely that
120
the evident decrease in the global prevalence of 2 major risk
15
factors for SAH resulted in the decline of its incidence.90 For
110
10
smoking alone, such an association has been recently re-
ported in a registry-based incidence study from Finland.3 How-
100 ever, it remains uncertain why the SAH incidence in Japan has
5
increased substantially, despite the concomitant global de-
0 90 cline. Hypothetically, this could be a consequence of the
1955 1965 1975 1985 1995 2005 2015
Midyear of Study
distinctly higher crude prevalence of smoking in Japan (26.1%)
compared with the global population (19.3%) in our data set.
B Incidence of SAH by smoking prevalence Unfortunately, the limited age-specific, sex-specific, midyear-
30 100
specific, and country-specific SAH incidence data did not
Time trend of SAH incidence
permit further regression analyses in this respect.
Incidence of SAH per 100 000 Person-Years

Smoking prevalence
25 Second, preventive repair of unruptured intracranial an-
80
eurysms (UIAs) could have resulted in a subsequent decrease
Smoking Prevalence, %

20 of SAH incidence in the underlying populations. However, we

15
10
5
0 0
1955 1965 1975 1985
Midyear of Study
A, Time trends in SAH incidence in all studies by midyear are presented
irrespective of age and sex (black dots). The black line indicates the
regression/time trend of SAH incidence with markers for mean estimated
incidence for 1980 and 2010. The blue line indicates mean systolic blood
pressure levels in studies included in the age-specific and sex-specific analyses,
with markers for mean estimated systolic blood pressure levels for 1980 and
2010. B, Time trends in SAH incidence in all studies by midyear are presented
irrespective of age and sex (black dots). The black line indicates the
regression/time trend of SAH incidence with markers for mean estimated
incidence for 1980 and 2010. The red line indicates smoking prevalence in
studies included in the age-specific and sex-specific analyses, with markers for
smoking prevalence in 1980 and 2010.
proportion of studies reporting specific data on aneurysmal
SAH incidence in that study may have been too limited to per-
mit robust analysis of time trends. For Finland, a country with
a previously reported high SAH incidence, no studies ful-
filled our inclusion criteria after 1990, and therefore we could
not assess a change over time. A recent register-based Finn-
ish study,3 which also did not fulfill our inclusion criteria, re-
ported an age-standardized decrease in SAH incidence by 24%
between 1998 and 2012 along with a simultaneous decrease
in smoking prevalence by 30%. The crude SAH incidence for
2010 in Finland was estimated in that study to be 9.1 per
100 000 person-years.3 This incidence is lower than our cur-
rent estimate for the pre-1990 studies (ie, 16.6 per 100 000 per-
son-years), which suggests that the incidence has also de-
60
consider it unlikely as the sole explanation because of the enor-
mous number of interventions that should have been per-
40 formed to reach such a reduction; to achieve a 10% reduction
in SAH incidence, at least 15 million UIAs should have been
20 treated preventively (assuming a UIA prevalence of 3% in the
adult population and 165 million UIAs worldwide). In the
United States alone, only about 12 000 Medicare patients un-
1995 2005 2015
derwent preventive aneurysm treatment in 1 decade.91 Third,
a decrease in the prevalence of UIAs over the past decades could
have resulted in a decline of SAH incidence, but such a trend
was not found in the most recent pooled analysis.92
Fourth, one could argue that our data on SAH incidence
time trends are explained by the trend of increased propor-
tions of CT scanning over time, which was the main explana-
tion for the decline in SAH incidence almost 2 decades ago.8
However, our sensitivity analyses underline that the decline
in SAH incidence in our study is genuine and is only partially
explained by the increased use of CT scanning over time, es-
pecially because of the generally high proportion of cranial
imaging (mean percentage of CT scanning, 89.6%) in studies
published after 1985. Theoretically, a change in incidence over
time within a population may also be caused by a change in
proportions of race/ethnicity within that population over time.
However, because none of the populations where incidence
was studied in several time periods provided data on change
in race/ethnicity over time within the population, we were not
able to further analyze this aspect.
Strengths and Limitations
A strength of our study is that it comprises, to our knowl-
edge, the most rigorous and geographically and chronologi-
cally dispersed data set on SAH incidence specifically and solely
derived from population-based studies to date. We had strict
inclusion criteria to ensure detection of patients dying before

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 Research Original Investigation Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage

reaching the hospital. Since we also found little variation in
case ascertainment and diagnostic criteria in our meta-
analysis and since the proportion of patients who die sud-
denly is around 12%, it is unlikely that the large regional
variation in incidence found in this systematic review is
explained only by differences in case finding and diagnostic
criteria between the studies. 93 Furthermore, our meta-
analysis is the first to our knowledge to find an association
of time trends of blood pressure and smoking prevalence
with SAH incidence.
Our study had limitations. There were limited population-
based data on SAH incidence for most of Africa and large East-
ern populations, including China, Russia, and India. We chose
the population-based study design over a registry-based de-
sign in favor of high-quality data and under the premise that
study populations are representative of the population of that
country. However, variations in SAH incidence on a regional
level may exist, which may not be captured by the study popu-
lation that represented a specific country. Further, a limita-
tion of such an ecological study design is that one cannot study
causal relationships on an individual patient level, and such
a design harbors the risk of confounding relations. We mini-
mized the risk of confounding by means of adjusted regres-
sion analyses. Nevertheless, we underline that our findings are
no more than associations and that causal relationships be-
tween decline in blood pressure or smoking prevalence and
SAH incidence can only be accurately studied when quanti-
tative data for these risk factors become available on a popu-
lation-based or individual patient level. Finally, not all pa-
tients with SAH included in the parent studies underwent
angiography. On the one hand, this may have led to an over-
estimation of the incidence because instances of nonaneurys-
mal SAH may have been included. On the other hand, restrict-
ing to angiographically confirmed aneurysmal SAH inevitably
induces an underestimation of the actual incidence because
not all patients reach hospitals alive, and in the pre-CT angi-
ography era, catheter angiography was only done if the
patient was eligible for aneurysm treatment.
Conclusions
The association we found between blood pressure and smok-
ing prevalence reduction with decrease in SAH incidence fur-
ther supports control of these risk factors to reduce SAH bur-
den. Future studies should address the regional differences in
SAH incidence and its decline, regional differences in age-
specific and sex-specific incidences, and their association with
actual quantitative data on smoking. Explanations for these
differences may help to further decrease SAH incidence. The
reasons for the increasing incidence of SAH in Japan remain
unclear.

ARTICLE INFORMATION
Accepted for Publication: December 7, 2018.
Published Online: January 19, 2019.
doi:10.1001/jamaneurol.2019.0006
Author Contributions: Dr Etminan had full access
to all of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis. Drs Etminan and
Chang contributed equally.
Study concept and design: Etminan, de Rooij, Rinkel,
Algra.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: Etminan, Chang.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Chang, Algra.
Administrative, technical, or material support:
Chang, Hackenberg.
Study supervision: Etminan, Algra.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This paper was presented
at the German Society for Neurointensive and
Emergency Medicine and the German Stroke
Society 35th Annual Meeting; January 19, 2019;
Berlin, Germany.
Additional Contributions: We sincerely thank
Majid Ezzati, FMedSci, and Bin Zhou, PhD, as well as
the Noncommunicable Disease Risk Factor
Collaboration group (http://www.ncdrisc.org) for
providing the detailed country-specific, age-
specific, and sex-specific blood pressure data of the
Noncommunicable Disease Risk Factor dataset.
Contributors were not compensated for their work.
We also thank the reviewers of our manuscript for
their comments, some of which urged us to do
additional analyses that yielded interesting and
novel findings and ultimately helped us to improve
the quality of our manuscript.
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