European Journal of Epidemiology (2006) 21:367–371
DOI 10.1007/s10654-006-9000-6
CARDIOVASCULAR DISEASE
Habitual green tea consumption and risk of an aneurysmal rupture subarachnoid
hemorrhage: A case–control study in Nagoya, Japan
Kazushi Okamoto
Department of Epidemiology, Aichi Prefectural College of Nursing and Health, Nagoya, Japan
Accepted in revised form 2 March 2006
Abstract. Background: Green tea, a popular beverage
in Japan, contains many polyphenolic antioxidants,
which might prevent cardiovascular disease. This
study is designed to determine whether the con-
sumption of green tea is associated with a reduced
risk for subarachnoid hemorrhage (SAH) using a
case–control study. Methods: Incident SAH cases
(n=201) were identified and individually matched by
age (±2 years) and gender to hospital (n=201) and
community controls (n=201) from April 1992 to
March 1997. Habitual regular tea consumption was
assessed with a structured questionnaire. Conditional
logistic regression models were used to compute odds
ratios adjusted for smoking, history of hypertension,
Key words: Subarachnoid hemorrhage, Tea consumption, Diet, Case–control study
Green tea is widely consumed in Asian countries,
especially in Japan. Green tea polyphenols have
various physiological roles, including antioxidative
[1, 2] antithrombogenic [3, 4], and antihypertensive
[5] activities. Some epidemiological studies have re-
ported a high flavonoid intake through green tea may
protect against cardiovascular disease [6–9].
Subarachnoid hemorrhage (SAH) is characterized
by the rupture of a cerebral aneurysm resulting from
focal weakness of the artery wall of the cerebral
artery wall [9, 10].
To the best of our knowledge, however, very little
is known about whether tea flavonoids may be pro-
tective against SAH resulting from the structural
fragility of the artery wall. We conducted a case–
control study to explore the relationship between
green tea consumption and the risk of SAH, using a
relatively large number of newly diagnosed patients
in Japan.
Material and methods
The methods were previously described in detail [11,
12]. Briefly, we recruited consecutive and incident 201
SAH patients admitted at two large medical hospitals
in Nagoya, Aichi Prefecture, Japan (Nagoya Daini
Red Cross Hospital and Nagoya City Higashi

Springer 2006
and educational levels. Results: The proportion of the
consumption of one time or more of tea per day was
higher in controls (70.9%) than in SAH patients
(60.3%). Multivariate analyses showed that green tea
consumption was inversely associated with SAH risk.
Subjects consuming <1, and ‡1 time per day had
adjusted ORs of 0.74 (CI: 0.34–1.58), and 0.56 (CI:
0.32–0.98) in comparison with non daily green tea
drinkers, respectively (p-trend <0.001). Conclusion:
In a case–control study in Japan, we found that
habitual green tea consumption may be strongly
associated with a reduced risk for SAH. Our findings
will be useful in targeting individuals and populations
for the primary prevention of SAH.
Municipal Hospital) from April 1992 to March 1997.
SAH was diagnosed by an aneurysmal bleeding pat-
tern on computed tomography (CT) with the addi-
tional requirement that the presence of one or more
aneurysms had to be confirmed by cerebral angiog-
raphy. All subjects experienced a first spontaneous
onset of SAH. Patients with were not eligible for this
study. SAH was according to standard criteria [13,
14], and we included only patients with proven rup-
ture of an intracerebral aneurysm by cerebral
angiography.
We set up community controls with no past history
of SAH, matching to each patient for age (±2 years)
and gender. The controls were randomly selected
from electoral of the same area as the SAH patients.
If potential control did not respond after one request,
another eligible candidate was selected.
Data collection
SAH patients and their matched controls were
interviewed by two investigators (K.O. R.H.). Direct
interviews were conducted for SAH patients at each
hospital and for community controls at their homes.
SAH patients were interviewed within a month after
their admission, and community controls within
2 weeks after their identification. We asked cases to
recall their lifestyle and food frequencies at the time
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5 years before the onset of SAH, and we asked con-
trols to recall their lifestyle before the interview, using
a structured questionnaire specifically designed for
the case–control study. Among SAH patients, eligible
cases were 75% of all admitted SAH patients. Of 268
potentially eligible cases, 42 (15.7%) had other causes
of SAH (e.g. traumatic and arterio-venous malfor-
mation), 8 (3.0%) was refused by the doctor, and173
(6.3%) had moved out of area. For community
controls, it was difficult to obtain the recruitment rate
because all community controls were not always
chosen in the same area. The same interviewer in-
volved in the pair of SAH patient and the matched
control.
When the patients were unable to provide any
information on their lifestyle and exposure because of
early death or impairment, proxies (mainly spouses)
were interviewed. Whenever possible, a standardized
in-person interview was conducted with the patients
and their matched controls. Only when this was not
possible was a proxy interview performed. To mini-
mize information bias, when the proxy to an SAH
patient was interviewed, the proxy to the control was
also interviewed even if the control was competent to
be interviewed.
Institutional ethics committees in each of the two
study hospitals approved the protocol before com-
mencement. All participants provided informed con-
sent, after verbal explanation of the study protocol
was provided.
Dietary information was obtained by a self-
administered food frequency questionnaire, consist-
ing of 97 commonly eaten food and beverage items.
The green tea question was phrased in the follow-
ing way: ‘How many times do you drink green tea
each day?’ The frequency of green tea consumption
was divided into five categories: ‘never/seldom’, ‘less
than 1 time/week’, ‘less than 3 times/week’, ‘‡3 times/
week’, and ‘‡1 time/day’. In this analysis, we classi-
fied into three categories of green tea consumption
based on the distribution among controls as follows:
‘never’ ‘<1 time/day’ and ‘‡1 time/day’.
Assessments of covariates
The questionnaire was included information on
demographic data (age at diagnosis, gender, educa-
tional level), medical history (episodes of hyperten-
sion), family history of SAH in any first-degree
relatives, smoking habits (current, ex-, and non-
smokers). Smoking status was categorized as current
smokers as current smokers or nonsmokers (includ-
ing ex-smokers).
Statistical analysis
Odds ratio (ORs) and 95% confidence intervals (CIs)
were estimated by the use of a multiple conditional
logistic regression model in which potential con-
founders (past episode of hypertension, smoking
status) were controlled [15].
Results
The characteristics of cases and two controls are
presented in Table 1. Since there was no difference
between hospital and community controls, the two
controls were combined for all analyses. SAH
patients had significantly higher proportions of
hypertensive subjects, current smokers and higher
education in comparison with controls. As Table 2
shows, subjects consuming <1, and ‡1 times per day
had adjusted ORs of 0.74 (95% CI: 0.34, 1.58), and
0.56 (95% CI: 0.32, 0.98) in comparison with never
drinkers, respectively (p for trend=0.0012). As
Table 3 shows, green tea consumption was signifi-
cantly associated with a decreased SAH risk only
among positive family history of SAH.
Discussion
In this case–control study, we found a significantly
inverse association with between daily consumption
of green tea, even after adjustment for confounding
variables. Subjects consuming ‡1 time per day had an
approximately 40% reduction in the risk of SAH,
compared with never drinkers, a trend that was sig-
nificant. This is the first case–control study investi-
gating the effect of tea consumption on the risk of
SAH.
Several studies analyzed combined stroke subtypes
[16–18] have indicted that tea consumption was sig-
nificantly associated with a decreased SAH risk. In
this study, we found that tea consumption has a
significant association with a decreased risk of SAH,
which is critical information for the formation of
plans for the primary prevention of SAH.
A few observational studies have suggested that tea
may have blood pressure-lowering effects [19–21].
These findings could be a possible explanation for
potentially protective mechanism of tea against the
development of focal weakness of the cerebral blood
artery wall resulting in SAH.
The potential effects of the ingestion of polyphe-
nolic components in green tea on the structural blood
artery wall are well established [1–5]. Duffy et al. [22].
suggests that tea may acts to improve endothelial
vasomotor function, increase the stimulus for dila-
tion, or improve vascular smooth muscle function.
We found that subjects with higher tea consumption
were significantly associated with a decreased risk of
SAH only among positive family history of SAH.
This finding strongly suggests that tea consumption
may inhibit focal weakness of artery wall, especially
for a positive family history of SAH.
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Table 1. Selected background characteristics of study subjects

Cases N=201 Controls p*

Hospital N=201 Community N=201 Combined N=402

No. (%) No. (%) No. (%) No. (%)

Sex
Men 77 (38.3) 77 (38.3) 77 (38.3) 144 (38.3) N.S.
Women 124 (61.7) 124 (61.7) 124 (61.7) 248 (61.7)
Age group
30–49 40 (19.9) 42 (20.9) 40 (19.9) 82 (20.4) N.S.
50–59 60 (29.9) 54 (26.9) 61 (39.3) 115 (28.6)
60–69 66 (52.8) 68 (33.8) 64 (31.8) 132 (32.8)
70–79 35 (17.4) 37 (18.4) 36 (17.9) 73 (18.2)
Mean age (SD) 59.2±10.3 59.1±10.5 59.0±10.2 59.1±10.4
Type of interview
Direct 137 (68.3) 137 (68.3) 137 (68.3) 274 (68.3)
Proxy 64 (31.7) 64 (31.7) 64 (31.7) 128 (31.7)
A history of hypertension 84 (47.8) 46 (26.0) 46 (25.0) 92 (24.8) 0.0000
Positive family history of SAH 29 (14.9) 10 (5.1) 9 (4.5) 19 (4.7) 0.0003
Current smoker 110 (55.6) 86 (44.3) 75 (37.6) 161 (37.6) 0.05
Educational level
Less than high school 46 (25.3) 72 (38.5) 80 (40.0) 152 (39.4) 0.0000
High school 85 (46.7) 95 (47.5) 97 (48.5) 192 (48.6)
College or more 51 (28.0) 28 (14.0) 23 (11.5) 51 (12.0)

*p value when comparing cases vs. combined controls.

N.S: Not significant.

Table 2. Odds ratios (OR) and 95% confidence interval (95% CI) for SAH by categories of green tea consumption

Cases/controls Crude ORsa 95% CI Adjusted ORsb 95% CI

Never 44/13 1.00 1.00

<1 time/day 35/36 0.71 0.40–1.07 0.74 0.34–0.93
‡1 time/day 122/152 0.58 0.26–0.68 0.56 0.32–0.98
p for trend p=0.000 p=0.0012
a
Logistic regression models conditional on age and gender.
b
Adjusted OR is that obtained from multivariate analyses adjusted for a history of hypertension, smoking habits, family
history of SAH and educational levels.

Table 3. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) for SAH by family history of SAH

Family history

Negative Positive

Adjusted ORsa 95% CI Adjusted ORsa 95% CI

Never 1.00 1.00

<1 time/day 0.78 0.21–1.08 0.58 0.28–1.30
‡1 time/day 0.56 0.22–0.98 0.38 0.32–0.95
p for trend p=0.06 p=0.02
a
Adjusted OR is that obtained from multivariate analyses adjusted for a history of hypertension, smoking habits, family
history of SAH and educational levels.

There are some limitations in the present study.
First, it was related to dietary assessment. We got
dietary information at the time 5 years before.
Thompson et al. reported retrospective report of diet
over the 15-year period was strongly related to the
current report of diet [23]. Second, we used SAH
patients admitted to hospitals as the case subjects,
resulting in potential biases, particularly in the case
selection. The two hospitals used in this study are
central hospitals in the eastern and the southern area
370
of the city. Almost all patients with severe or acute
medical conditions such as SAH are admitted to these
hospitals. In addition, community controls were
randomly selected from among the inhabitants
residing in the same areas as our case subjects. Third,
in this study questionnaire information was provided
by proxy respondents in approximately one third of
the cases. As previously reported, however, proxy
respondents provided acceptable information for
smoking [24], episode of hypertension [24] and die-
tary information [25]. Moreover, the associations
were unaltered after the data were reanalyzed with
the exclusion of data obtained from proxy respon-
dents or deceased subjects (data not shown).
Several strengths of the present investigation war-
rant mention here. First, all cases were newly diag-
nosed, and included not only live cases, but also
deceased ones to avoid the effect of survival bias.
Second, bias due to disease misclassification is also
unlikely because our cases were exclusively due to
aneurysmal SAH diagnosed by cerebral angiography
and CT, and no SAH events were involved in the
controls.
In conclusion, our findings suggest that habitual
green tea consumption may act protectively against
SAH. Our findings will be useful in targeting indi-
viduals and populations for the primary prevention
of SAH.
Acknowledgements
We are very thankful to the staffs of the Department
of Cranial Nerve Surgery and Alimentary disease,
Nagoya Daini Red Cross Hospital and of the
Department of Cranial Nerve Surgery Nagaya City
Higashi Municipal Hospital for successful and
coordination in data collection.
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Address for Correspondence: K. Okamoto, Department of
Epidemiology, Aichi Prefectural College of Nursing and Health,
Togoku, Kamishidami, Moriyama-ku, 463-8502, Nagoya, Japan
Phone: +81-52-736-1401; Fax: +81-52-736-1415
Email: okamoto@aichi-nurs.ac.jp
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