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Background: Whereas high body mass index (BMI) is reportedly a risk factor for
cardiovascular events in Western countries, low BMI has been reported as a risk factor
for cardiovascular death in Asia, including Japan. Although subarachnoid hemorrhage
(SAH) is a highly fatal disease and common cause of disability, few cohort studies
have examined the associations between BMI and SAH in Japan. This study investigated
the associations between BMI and incidence of SAH using prospective data from
Japanese community residents. Methods: Data were analyzed from 12,490 participants
in the Jichi Medical School Cohort Study. Participants were categorized into 5 BMI
groups: ≤18.5, 18.6-21.9, 22.0-24.9, 25.0-29.9, and ≥30.0 kg/m2. Multivariate-adjusted
hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox pro-
portional hazard model with BMI of 22.0-24.9 kg/m2 as the reference category. Results:
During the mean follow-up period of 10.8 years, 55 participants (13 men, 42 women)
experienced SAH. BMI ≥30.0 kg/m2 was associated with significantly higher risk
for SAH (HR, 5.98; 95% CI, 2.25-15.87). BMI ≤18.5 kg/m2 showed a nonsignificant
tendency toward high risk of SAH (HR, 2.51; 95% CI, .81-7.79). Conclusions: High
BMI was a significant risk factor for SAH. Lower BMI showed a nonsignificant ten-
dency toward higher risk of SAH. Our results suggest a J-shaped association between
BMI and risk of SAH incidence. Key Words: Body mass index—subarachnoid
hemorrhage—community-based cohort study—Japanese population.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Introduction
From the *Graduate School of Saitama Prefectural University,
Koshigaya, Saitama, Japan; †Department of Clinical Laboratory Med- Subarachnoid hemorrhage (SAH) was responsible for
icine, Department of Public Health, Jichi Medical University,
the deaths of almost 12,476 people in 2015 in Japan,1 and
Shimotsuke, Tochigi, Japan; and ‡Division of Community and Family
Medicine, Center for Community Medicine, Jichi Medical University,
the estimated annual number of patients was 36,000 in
Shimotsuke, Tochigi, Japan. 2011.2 The rate of acute case fatality for SAH is very high
Received November 29, 2016; revision received February 22, 2017; (40%-60%),3,4 particularly among the young.
accepted March 23, 2017. Body mass index (BMI) is used as a measure of body
Grant support: This study was supported in part by a Grant-in-Aid
fat metabolism and has been used to define obesity, over-
from the Foundation for the Development of the Community, Tochigi,
Japan, and by a Grant-in-Aid for Scientific Research; JSPS KAKENHI
weight, and leanness in many epidemiologic studies. This
Grant Numbers JP10470113, JP15390209, JP18390198, JP18590607. index has been recognized as an important risk factor
Address correspondence to Motohiko Hara, MD, Saitama Prefectural for the development of cardiovascular diseases (CVD).
University, 820 Sannomiya, Koshigaya, Saitama 343-8540, Japan. E-mail: Nevertheless, limited information is available regarding
hara-motohiko@spu.ac.jp.
the association between BMI and SAH in community-
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All
based cohort studies. Some European cohort studies have
rights reserved. shown that subjects with high BMI had a low risk of
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.03.029 SAH,5,6 but the results were not statistically significant.
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
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2 N. KAWATE ET AL.
A meta-analysis of 26 Asian-Pacific cohorts suggested BMI
had no significant association with SAH.7
To the best of our knowledge, only 2 cohort studies
have reported on the association between BMI and SAH
in Japan. The Japan Collaborative Cohort (JACC) study
showed low BMI as a risk factor for SAH mortality.8
However, another study reported a nonsignificant trend
toward an association between BMI and incidence of
SAH.9 The significance of BMI as a risk factor for SAH
incidence thus remains controversial.
This study examined the association between BMI and
spontaneous SAH incidence in Japanese community
residents using data from the Jichi Medical School Cohort
Study.
≤18.5 18.6-21.9 22.0-24.9 25.0-29.9 ≥30.0 P* ≤18.5 18.6-21.9 22.0-24.9 25.0-29.9 ≥30.0 P*
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Men Women
No. of subjects 190 1533 1725 932 64 365 2272 2567 1569 187
Age, years 59.6 55.3 54.9 53.3 53.3 <.01 55.2 53.3 55.8 56.8 55.4 <.01
(13.4) (12.5) (11.5) (11.0) (11.5) (14.6) (12.2) (10.2) (9.6) (9.1)
Systolic blood pressure, mm Hg 123.6 126.6 132.1 138.2 145.0 <.01 118.3 122.4 129.3 135.3 140.6 <.01
(20.7) (19.8) (19.9) (19.9) (20.1) (20.5) (19.9) (20.1) (20.5) (21.5)
Serum cholesterol concentration
Total cholesterol, mg/dL 171.6 178.3 187.2 193.7 202.2 <.01 186.4 191.5 197.9 204.5 206.1 <.01
(30.8) (33.2) (33.0) (34.8) (36.9) (35.5) (34.5) (34.2) (34.3) (34.4)
High-density lipoprotein cholesterol, mg/dL 55.3 52.4 48.0 43.8 40.9 <.01 58.6 55.6 51.8 48.9 47.2 <.01
(15.5) (13.3) (13.0) (11.5) (11.6) (13.3) (12.4) (12.2) (11.3) (10.9)
Triglycerides, mg/dL 88.5 103.5 130.8 167.1 221.5 <.01 83.0 91.6 111.8 135.7 150.5 <.01
(58.4) (72.7) (80.1) (101.3) (150.5) (43.8) (48.4) (63.7) (85.5) (89.2)
Diabetes mellitus†, % 4.2 4.2 4.4 5.1 7.8 .57 1.7 1.4 1.6 2.1 9.6 <.01
Current smoker, % 62.2 57.4 47.2 44.8 45.8 <.01 8.5 6.9 4.2 4.9 8.1 <.01
Current alcohol drinker, % 65.2 76.4 76.9 74.9 56.6 <.01 32.4 33.2 34.9 33.5 30.7 .61
N. KAWATE ET AL.
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BODY MASS INDEX AND SUBARACHNOID HEMORRHAGE IN JAPAN 5
Table 2. Hazard ratios (HR) and 95% confidence intervals (CI) for subarachnoid hemorrhage based on body mass index and
adjusted for potential confounders
HR1, hazard ratios adjusted for age and sex; HR2, hazard ratios adjusted for age, sex, systolic blood pressure, total cholesterol, high-
density lipoprotein cholesterol, triglycerides, diabetes mellitus, smoking, and alcohol consumption.
*Per 100,000 person-years.
follow-up period, and some baseline characteristics of the decreased with increasing BMI level in Western studies,
JACC study were similar to those in our study. Sex ratios but increased in Asian studies. Ethnicity could partly
(men:women) for SAH cases in both previous studies were explain the differences in the results between Western
approximately 1:2, compared with 1:3 in our study. Case studies and Asian studies, including our study.
certification of SAH in the JACC study was inferred from Epidemiologic studies in Japan and Western coun-
the death registration under the Family Registration Law. tries have reported the risk factors for SAH such as female,
These differences between previous studies from Japan hypertension,7-9,14,16,21-23 smoking,24 heavy alcohol drink-
and our own could explain inconsistencies in the results. ing, high coffee consumption,25 high mental stress, high
In Europe and Asia, several population-based cohort salt intake, family history of stroke, history of blood trans-
studies have examined BMI and SAH risk. A cohort study fusion, and low temperature and high atmospheric pressure
in Finland showed BMI was inversely associated with in winter.8,9,21-23,25,26 On the other hand, hypercholesterol-
risk of SAH.5 The HUNT study in Norway reported a emia decreased the risk of SAH.21 After adjusting for some
U-shaped relationship, with the group with BMI 25-29.9 of these factors, our results remained statistically signif-
showing the lowest risk.14 Two large-scale prospective icant. Our study could identify new epidemiologic findings.
studies using a nationwide database of medical record The strength of our study was that SAH incidence was
for about 1 million individuals were conducted in British evaluated based on a large Japanese cohort study that
women6 and Korean men.15 The former showed de- included both sexes. Data were obtained in a standard-
creased SAH risk with increased BMI. In contrast, the ized manner. Validated cases of CVD among annual health
latter reported a nonsignificant association between BMI examination participants who had no history of CVD at
and SAH risk. A pooled analysis of 26 cohorts from eastern baseline examinations were included. The diagnosis of
Asia and Oceanian countries failed to identify BMI as a SAH was made by an independent committee using ac-
significant risk for SAH.16 cepted diagnostic criteria, minimizing the possibility of
In a nested case-control study in Norway,17 the odds information bias.
ratios of SAH did not differ significantly among BMI Several limitations to this study must be considered.
groups. Two case-control studies in the United States18,19 Although study participants were selected from a
reported the inverse relationship between BMI and SAH population-based health examination, selections were not
risk, whereas no significant association was revealed in random. Selection bias is problematic if response rate is
an Australian study.20 low. In this study, the response rate for the target pop-
These studies varied in study design, implementation ulation (62.7%) would be considered rather high.10 However,
period, and case identification procedure. Furthermore, the selection bias could exist to some extent. Among health
age, sex ratio, BMI, SAH incidence, and ethnicity of sub- examination participants, the proportions treated for hy-
jects all differed with our own. The group with the lowest pertension, DM, or dyslipidemia were lower than those
BMI was categorized as <18.5 kg/m2 in Asian studies, reported in a national health and nutrition examination
compared with about 23 kg/m2 in European and North survey.27 Participants in this study thus appeared some-
American studies. BMI ≥30 kg/m2 accounted for over 10% what healthier than the general population. Smoking status,
of subjects in the HUNT study, whereas 2.1% of the sub- alcohol drinking status, and history of medication were
jects were in the group with BMI ≥30 kg/m2 in our study. all self-reported, and BMI was calculated based on body
A meta-analysis suggested the risk of hemorrhagic stroke weight of the fully clothed subject; therefore, some
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6 N. KAWATE ET AL.
inaccuracies can be expected. Compared with the Western men and women. Nippon Eiseigaku Zasshi 1999;53:587-
studies, the small number of participants with BMI 595.
≥30.0 kg/m2 reduced our statistical power to evaluate risk 10. Ishikawa S, Gotoh T, Nago N, et al. The Jichi Medical
School (JMS) Cohort Study: design, baseline data and
among obese subjects. The number of male incident cases standardized mortality ratios. J Epidemiol 2002;12:408-
(13) was small so that risk estimation for men was limited. 417.
Finally, a high prehospital mortality rate could make SAH 11. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification
diagnosis difficult. During follow-up, we documented 41 of subtype of acute ischemic stroke. Definitions for use
cases of sudden death, defined as death within 24 hours in a multicenter clinical trial. Stroke 1993;24:35-41.
12. WHO MONICA Project Principal Investigators. The World
after symptom onset. However, all cases of sudden death Health Organization MONICA project (monitoring trends
were reviewed carefully by the diagnostic committee to and determinants in cardiovascular disease): a major
rule out SAH. international collaboration. J Clin Epidemiol 1988;41:105-
114.
13. Committee of Criteria for Obesity Disease in Japan.
Conclusion Criteria for obesity disease in Japan 2011. J Jpn Soc Stud
In this community-based cohort study, the group with Obes 2011;17(Suppl):1-78.
14. Sandvei MS, Romundstad PR, Müller TB, et al. Risk
BMI ≥30.0 kg/m2 was at significantly higher risk of SAH.
factors for aneurysmal subarachnoid hemorrhage in a
Our results suggest a J-shaped association between BMI prospective population study: the HUNT study in
and risk of SAH incidence. This result could provide po- Norway. Stroke 2009;40:1958-1962.
tentially useful information to stimulate further studies 15. Song Y-M, Sung J, Davey Smith G, et al. Body mass index
regarding associations between BMI and SAH incidence and ischemic and hemorrhagic stroke: a prospective study
in Korean men. Stroke 2004;35:831-836.
among community residents.
16. Feigin VL, Rinkel GJE, Lawes CMM, et al. Risk factors
for subarachnoid hemorrhage: an updated systematic
Acknowledgments: We are grateful to the 12,490 dedicated review of epidemiological studies. Stroke 2005;36:2773-
and conscientious participants of the Jichi Medical School 2780.
Cohort Study, as well as the physicians, public health nurses, 17. Isaksen J, Egge A, Waterloo K, et al. Risk factors for
aneurysmal subarachnoid haemorrhage: the Tromsø study.
and local government officials. We also thank Professor Midori
J Neurol Neurosurg Psychiatry 2002;73:185-187.
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