REVIEWBlood Cholesterol Level and Risk of Stroke in Community-basedor Worksite Cohort Studies: A Review of Japanese Cohort Studies
in the Past 20 years
Taichiro Tanaka1 and Tomonori Okamura2
1 Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering,

University of Yamanashi, Yamanashi, Japan

2 Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan(Received for publication on September 5, 2011)(Revised for publication on October 26, 2011)(Accepted for publication on November 17, 2011)

Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD)
has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan.
We therefore reviewed cohort studies that investigated this relationship in the Japanese population
over the past 20 years, and compared their findings with clinical trials and cohort studies in Westerncountries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects
in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years.
The majority of studies showed no association between hypercholesterolemia and total stroke. However,
one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may
be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized
controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Twohypotheses have been proposed to explain this association between low cholesterol and intracerebral
hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further
continuous research in various fields of medical science is required to clarify the overall effect of blood
cholesterol on stroke in humans. (Keio J Med 61 (3) : 79–88, September 2012)

Keywords: cholesterol, stroke, cohort studies, cerebral infarction, intracerebral hemorrhage

Introduction

ity developed countries. Furthermore, some U.S. cohort
studies have suggested that non-high-density lipoproteincholesterol (non-HDLC) may be a better predictor of
CAD.5,6 Non-HDLC reflects the total cholesterol concentration of all atherogenic lipoproteins and is calculated bysubtracting the level of high-density lipoprotein cholesterol (HDLC) from that of TC. The Health and Medical
Service Law for the Elderly was enacted in 1982, and as

The causal relationship between coronary artery disease (CAD) and high serum levels of total cholesterol(TC) or low-density lipoprotein cholesterol (LDLC) is
well established.1–4 Serum cholesterol levels are therefore
the main target for lipid management and prevention ofatherosclerotic disease in the guidelines of the major-

Reprint requests to: Tomonori Okamura, MD, PhD, Department of Preventive Medicine and Public Health, School of Medicine, Keio University,
35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, E-mail: okamura@z6.keio.jp
Copyright © 2012 by The Keio Journal of Medicine
79

80

a result, all Japanese citizens aged 40 years and over have
had the opportunity to undergo screening for TC from1986 and screening for HDLC from 1992. Citizens withdyslipidemia are also provided with health services suchas health education to prevent CAD. For this screening
system, the basis was changed from TC to LDLC in April
2008.
In contrast, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite
stroke being the most common cardiovascular disease inJapan.7 There is evidence that the mean cholesterol levelin the Japanese population has been lower than that inmost Western countries for many decades and this is associated with a lower CAD mortality than in Western
populations.7 However, to clarify the relationship between hypercholesterolemia and stroke it is necessary to
carry out original cohort studies. This review article focuses on a series of cohort studies performed in Japanesecommunity-based or worksite populations. These studies
provide evidence that partially establishes the long-held,
but unconfirmed, belief that hypercholesterolemia is associated with stroke.
Overview of Japanese Cohort Studies Carried Out
in the Past Two Decades
We performed a PubMed literature search of studies
published between January 1991 and August 2011. We
used the search terms “cholesterol” in combination with“cerebrovascular disease or stroke,” “Japan or Japanese”
and “cohort studies.” Studies were selected using the following criteria: (1) reports were published in English, (2)studies were performed in Japan, (3) studies were of theprospective cohort type (including nested case–control
studies), and (4) statistical analyses were carried out on
the relationship between cholesterol levels (TC, LDLC,
non-HDLC) and stroke endpoint (fatal and/or non-fatal
stroke including its subtypes) adjusted at least for age andhypertension (including blood pressure levels). Finally,
we selected potentially relevant articles based on the title
and the abstract, and obtained the full text of these articles for detailed review.
Table 1 summarizes the cohort studies carried out on
Japanese populations over the past 20 years, listed inchronological order of date of publication. Of the 14 studies,8–21 2 studies were on worksite populations8,18 and theremaining 12 studies were on residents of various communities. All but one of the studies were cohort studies, the exception being a nested case–control study.13
The number of subjects ranged from 1621 to 91,219, andthe mean or median follow-up periods ranged from 7.6
to 32 years. In the cohort studies, the endpoint in eightstudies was the first occurrence of stroke and/or its subtypes during the follow-up period,8–10,14–16,18,19 and in six
studies, the endpoint was death due to stroke and/or its
subtypes.11–13,17,20,21 Apart from two studies,10.16 all the

Tanaka T and Okamura T: Blood Cholesterol and Stroke

investigations also examined the relationship between
TC (or LDLC or non-HDLC) and myocardial infarction(MI) or CAD. A positive association between hypercholesterolemia and CAD was shown in all but two of thestudies20,21 (data not shown in the table). In contrast, themajority of studies showed no association between hypercholesterolemia and total stroke events. Furthermore,some studies reported that community residents with low
serum TC or LDLC levels were more likely to develop
intracerebral hemorrhage.11–13,17,21 Only one recent reportfrom the Hisayama study showed a positive association
between LDLC and atherothrombotic cerebral infarction.15 Several of the above-mentioned studies are discussed in more detail below.
Summary of Key Studies
1. NIPPON DATA80
The cohort studies of the National Survey on Circulatory Disorders, 1980, Japan, are referred to as NIPPONDATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends
in the Aged, 1980).11,12 The baseline surveys were performed in 1980. In 1980 approximately 10,000 community residents aged 30 years or older from 300 randomly
selected districts participated in a survey. Figure 1 shows
the relationship between TC and death due to CAD in
the 17.3-year follow-up period of NIPPON DATA80.12 A
positive, graded relationship was observed between thetwo parameters in men. Although a graded relationshipwas not observed in women, the group with the highest
TC had a significantly increased risk of death from CAD.
In contrast, there was no association between TC and therisk of stroke mortality (Fig. 2). Limited analysis showed
there was also no association between TC and death due
to cerebral infarction. However, this study had some limitations. The first is the possible misclassification of stroke
diagnosis because the endpoints were determined fromdeath certificates. The second is that TC includes HDLC,a protective factor for atherosclerosis. These issues were
therefore addressed by other cohort studies.
2. The Suita study
The Suita study was established in 1989 and invited
12,200 Japanese urban residents of Suita City, Osaka, toparticipate. The participants were 30–79 years old andwere selected randomly from the municipal population
registry. Of these, 6485 men and women took part in abaseline medical examination at the National Cardiovascular Center between September 1989 and February 1994.
The endpoints of this study were the first incidence of MI
or stroke. In this study,14 the relative risk for MI in the top
quintile of LDLC (≥151 mg/dl in men and ≥164 mg/dl inHisayama
Study

NIPPONDATA80

Okamura T, et al. 12

Imamura T, et al. 15

NIPPONDATA80

Okamura T, et al. 11

Suita
Study

Hisayama
Study

Tanizaki Y, et al. 10

Okamura T, et al. 14

ShibataStudy

Nakayama T, et al. 9

JACC
Study

-

Kitamura A, et al.8

Cui R, et al. 13

Study
name

Author

2009

2009

2007

2007

2003

2000

1997

1994

2351 men and women(Community)

345 cases and 345
controls from 39,242
men and women of acohort study.
(Community-basednested case–control
study)
4694 men and women(Community)

9216 men and women(Community)

9216 men and women(Community)

1621 men and women(Community)

6408 men(Worksite)2302 men and women(Community)

Publication year Number of subjects

19

11.9

10

17.3

13.2

32

15.5

7.7

Follow-up
years
TC and total stroke: No relationship.

Results concerning stroke

Incidence of total stroke and cerebral infarction. LDLC and total stroke: No relationship.
LDLC and cerebral infarction: No relationship.
Non-HDLC and total stroke: No relationship.
Non-HDLC and cerebral infarction: No relationship.
LDLC and total stroke: No relationship.
Incidence of total stroke, cerebral infarction
and its subtypes (cardioembolic, lacunar, andLDLC and cerebral infarction: No relationship.
atherothrombotic) and hemorrhagic stroke
LDLC and atherothrombotic type: Positive
relationship.
(subarachnoid hemorrhage and intracerebral
hemorrhage).
LDLC and lacunar type: No relationship.
LDLC and cardioembolic type: Inverse relationship.
LDLC and hemorrhagic stroke: No relationship.

TC and all total stroke: No relationship.
TC and cerebral infarction: No relationship.
TC and intracerebral hemorrhage: No relationship.
Incidence of cerebral infarction and its subTC and cerebral infarction: No relationship.
types: cardioembolic, lacunar, and atherothrom- TC and lacunar type: No relationship.
botic.
TC and atherothrombotic type: No relationship.
TC and cardioembolic type: No relationship. inmen and inverse relationship in women.
Death due to total stroke, intracerebral hemor- TC and total stroke: No relationship.
rhage, and cerebral infarction.
TC and cerebral infarction: No relationship.
TC and intracerebral hemorrhage: Inverse
relationship in men.
Death due to total stroke, intracerebral hemor- TC and total stroke: No relationship.
rhage, and cerebral infarction.
TC and cerebral infarction: No relationship.
TC and intracerebral hemorrhage: Inverse
relationship.
Death due to total stroke, subarachnoid hemor- TC and total stroke: Inverse relationship.
rhage, intracerebral hemorrhage, and cerebral TC and intracerebral hemorrhage: Inverse
infarction.
relationship.
TC and subarachnoid hemorrhage: No relationship.
TC and cerebral infarction: No relationship.

Incidence of total stroke, cerebral infarction,
intracerebral hemorrhage, and subarachnoid
hemorrhage.

Incidence of total stroke.

Endpoints for stroke

Table 1 Overview of community-based or worksite cohort studies investigating blood cholesterol levels and stroke in Japan published between January 1991 and August
2011*

Keio J Med 2012; 61 (3): 79–88
81-

Tsuji H, et al. 21
2011

2011

2010

2010

2009

2009

16,461 men and
women(Community)

12,334 men and
women(Community)

1794 men(Worksite)
22,430 men and
women(Community)

12,276 men and
women(Community)
91,219 men and
women(Community)

Publication year Number of subjects

10.9

11.9

7.6

12

10.3

10.7

Follow-up
years
Results concerning stroke

Death due to total stroke, hemorrhagic stroke(subarachnoid hemorrhage and intracerebral
hemorrhage),and cerebral infarction.
Death due to total stroke, hemorrhagic stroke(subarachnoid hemorrhage and intracerebral
hemorrhage),and cerebral infarction.

Incidence of total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral
infarction.

Incidence of total stroke.

Death due to total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral
infarction.

TC and total stroke: Inverse relationship.
TC and hemorrhagic stroke: Inverse relationship.
TC and cerebral infarction: Inverse relationship.

TC and total stroke: No relationship.
TC and cerebral infarction: No relationship.
TC and intracerebral hemorrhage: No relationship.
TC and subarachnoid hemorrhage: No relationship.
Non-HDLC and total stroke: No relationship.
Non-HDLC and cerebral infarction: No relationship.
Non-HDLC and intracerebral hemorrhage: No
relationship.
Non-HDLC and subarachnoid hemorrhage: No
relationship.
TC and total stroke: No relationship.
TC and hemorrhagic stroke: No relationship.
TC and cerebral infarction: No relationship.

LDLC and total stroke: Inverse relationship.
LDLC and subarachnoid hemorrhage: No
relationship.
LDLC and intracerebral hemorrhage: Inverse
relationship.
LDLC and cerebral infarction: No relationship.
TC and total stroke: No relationship.

Incidence of total stroke and cerebral infarction. TC and total stroke: No relationship.
TC and cerebral infarction: No relationship.

Endpoints for stroke* Although the nomenclatures of subtypes of stroke were not unified among the cohort studies, they are unified in this table for the reader’s convenience.
**Serum LDLC levels in this cohort were calculated by the Friedewald formula, with the majority of serum samples being collected in the non-fasting state.
NIPPON DATA, National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged; JACC Study: The Japan Collaborative Cohort Study;
JMS Cohort Study, Jichi Medical School Cohort Study; JALS Study, Japan Arteriosclerosis Longitudinal Study.
TC, total cholesterol; LDLC, low-density lipoprotein cholesterol; non-HDLC, non-high-density lipoprotein cholesterol.

JMS
cohortstudy

Nago N, et al. 20

Tanabe N, et al. 19

Li Q, et al. 18

YKK
study
JALS
Study

JMS
CohortStudy
IbarakiPrefectural Cohort
Study

Ishikawa S, et al. 16

Noda H. et al. 17 **

Study
name

Author82
Tanaka T and Okamura T: Blood Cholesterol and Stroke

Keio J Med 2012; 61 (3): 79–88

83

Fig. 1 Total cholesterol and coronary mortality data from NIPPON DATA80.
Multivariable-adjusted relative risk (RR) for coronary artery disease (CAD) mortality grouped according
to serum total cholesterol (TC) after adjustment for age, serum albumin, body mass index, hypertension,
diabetes, cigarette smoking, and alcohol intake. RR data are shown as black bars for men and white bars for
women (from Okamura T, et al.12). *P< 0.05 vs. reference group.

Fig. 2 Total cholesterol and stroke mortality data from NIPPON DATA80.
Multivariable-adjusted relative risk (RR) for stroke mortality grouped according to serum total cholesterol (TC) after adjustment for age, serum albumin, body mass index, hypertension,
diabetes, cigarette smoking, and alcohol intake. RR data are shown as black bars for men andwhite bars for women (from Okamura T, et al.12). No group has significantly lower or higher
RR than the reference group.

women) was approximately three times that in the lowest
quintile (<98 mg/dl in men and <106 mg/dl in women).
Similar results were also observed for non-HDLC. However, there was no correlation between the incidence ofany subtype of stroke and either LDLC or non-HDLC.
The relationship between serum lipids and cerebral infarction warrants further investigation because the study
did not evaluate the effect of serum LDLC or non-HDLC

84

Tanaka T and Okamura T: Blood Cholesterol and Stroke

Fig. 3 Low-density lipoprotein cholesterol (LDLC) and atherothrombotic type cerebral infarction in the
Hisayama study.
Pie chart (left) showing the proportion of each subtype of cerebral infarction detected during 19 years offollow-up in the Hisayama study. The bar graph (right) shows the relationship between LDLC and relativerisk (RR) of atherothrombotic cerebral infarction. Each bar shows RR stratified by LDLC quartiles after
adjustment for age, sex, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, ECG
abnormalities, fasting blood glucose, body mass index, current drinking, current smoking, and regularexercise (from Imamura T, et al.15). *P< 0.05 vs. bottom quartile.

on each subtype of cerebral infarction due to the small
number of stroke cases, especially for atherothrombotic
cerebral infarctions.
3. The Hisayama study
A cohort study in the town of Hisayama in Fukuoka
Prefecture has been ongoing since 1961 and is the most
famous cohort study on cardiovascular disease in Japan.
In this study, when stroke or CAD occurs or is suspected, physicians in the study team examine the subject andevaluate his/her detailed clinical information. Furthermore, when a subject dies, an autopsy is performed at the
Department of Pathology of Kyushu University. In thereference study,15 a total of 2351 residents were followedup for 19 years. Analysis showed that the association between LDLC and the incidence of total stroke, cerebral
infarction, or hemorrhagic stroke (subarachnoid hemorrhage and intracerebral hemorrhage) was not significant.
However, the risk of atherothrombotic cerebral infarction, which represented about one-fourth of all cerebral
infarctions, was increased significantly for the fourth
quartile of LDLC compared with the first quartile (Fig.
3). In addition, this is the first study in a Japanese population to show an inverse association between LDLC andcardioembolic cerebral infarction. The only limitationin this cohort study is its small number of participants.
However, a sufficient number of stroke events have been
observed due to the long follow-up period of the study.
Cohort Studies in Western Populations
As described above, the majority of cohort studies in Japan failed to demonstrate a positive relationship between
hypercholesterolemia and stroke. In contrast to the universally established evidence that hypercholesterolemia
is associated with an increased risk of CAD, the effectof hypercholesterolemia on cerebral infarction remains
controversial, even in Western populations. For example,
a positive association between TC and cerebral infarction
was observed in the multiple risk factor intervention trial(MRFIT) in the U.S.22 and in the Copenhagen City Heart
Study in Europe.23 However, the Atherosclerosis Risk in
Communities Study (ARIC study) showed that TC was
not associated with increased risk of total cerebral infarction,24 although hypercholesterolemia was associatedwith non-lacunar, non-embolic stroke (i.e., atherothrombotic stroke). Similar results were observed in the Hisayama study.15 A very large meta-analysis of individual
data from 61 prospective studies, most of which were car-

Keio J Med 2012; 61 (3): 79–88

85

Fig. 4 Putative issues in study design for cohort studies and clinical trials [randomized controlled trials(RCTs)].
In RCTs, there is no information on whether the participants are representative of the parent population.
Furthermore, clinical trials may be affected by pleiotropic or off-target effects of each medicine. In contrast, it is possible to accurately calculate the participation rate of the parent population in cohort studies,
although theoretically, cohort studies cannot control for unknown confounding factors.

ried out in U.S. and European populations, showed no independent positive association between TC and ischemic
and total stroke mortality.25 Consequently, in cohort studies, the relationship between hypercholesterolemia andcerebral infarction may be modified by the proportion ofatherothrombotic infarctions in the population surveyed.
In a population or country with a low proportion of atherothrombotic cerebral infarctions, the relationship between hypercholesterolemia and cerebral infarction may
be difficult to detect. However, from the viewpoint of patients and the general population, hypercholesterolemia
should be thought of as a risk factor for stroke because it
does seem to affect the risk of some types of stroke.
Randomized Controlled Trials
Recent randomized controlled trials (RCTs) have shownthat statins used as either primary26 or secondary prevention27substantially reduced levels of CAD and cerebral
infarction. Statin therapy has also been shown to successfully decrease the risk of cerebral infarction or composite

outcome of CAD or cerebral infarction in Japanese trials.28,29 However, caution is needed when interpreting theresults of these clinical trials. First, although there havebeen numerous clinical trials on statin therapy, the primary endpoint of these studies was CAD, with cerebral
infarction usually being the secondary endpoint in the
protocols. To our knowledge, only the Stroke Prevention
by Aggressive Reduction in Cholesterol Levels (SPARCL) was designed with stroke as the primary endpoint.30
Second, statins have well-known pleiotropic effects thatprevent cardiovascular disease. These include anti-inflammatory effects, an improvement in vascular endothelial function, and plaque stabilization. This may be a reason why we observed a significant discrepancy between
the results of cohort studies and clinical trials.31 However,a recent meta-analysis indicated that further reductions in
LDLC result in further decreases in the incidence of cerebral infarction with no evidence of any lower threshold. 32
An ongoing clinical trial to examine whether the additionof ezetimibe to statin therapy improves cardiovascularoutcomes compared with statin alone may provide in-86

Tanaka T and Okamura T: Blood Cholesterol and Stroke

formation concerning the pleiotropic effects of statins. 33
Because both RCTs and cohort studies have fundamental
limitations, it is important to take the findings from bothstudy designs into account. The RCT design provides noinformation as to whether the participants are representative of the parent population, whereas this may be clear
in cohort studies. In community-based or worksite cohort
studies it is also possible to calculate the participation rateof the parent population. To examine weak associations
suggested by cohort studies, such as that between hypercholesterolemia and stroke, it is necessary to use caution
and prudence when interpreting the results of clinical trials, even those with an RCT design. The putative issues inboth types of study design are summarized in Figure 4.
Risk of Low Blood Cholesterol Levels
Five out of 14 studies in Table 1 observed an inverse
relationship between serum TC (or LDLC) and hemorrhagic stroke, mainly intracerebral hemorrhage.11–13,17,21
In 1990, a National Heart, Lung, and Blood Institute(NHLBI) Conference was held to discuss the associations
between low blood cholesterol and non-coronary mortality.34 The conference concluded that most of the inverse
associations between cholesterol and non-coronary mortality, such as cancer, could be explained by reverse-causality such as pre-existing disease, unadjusted confounding factors, and socio-economic status. However, thisreport recommended that further studies should be undertaken on causal mechanisms linking low TC and hemorrhagic stroke. Several hypotheses have been proposed
to explain the inverse association between cholesterol andintracerebral hemorrhage.35 First, low blood cholesterol
may induce angionecrosis, possibly in association withhypertension; however, experimental evidence of this effect is limited. Second, low blood cholesterol may reflect
poor nutritional status, which is known to be related todeath after onset of stroke, but not to onset per se. The
inverse association between cholesterol and hemorrhagic
stroke is most commonly observed when stroke mortality is the endpoint in cohort studies. Third, there may besome residual confounding factors. In the majority ofclinical trials on statin therapy, it is very rare for an increase in intracerebral hemorrhage to be observed during
trials. However, in the SPARCL study that used strokeas the primary endpoint, hemorrhagic stroke was more
frequently observed in patients treated with statins, especially in those with a past history of hemorrhagic strokeor hypertension.30 Further research is needed in various
fields of medical science to validate these hypotheses andalso to explain the findings of the SPARCL study.
The Hisayama study15 and probably one other study21
showed an inverse relationship between blood cholesterol
and cardioembolic cerebral infarction. We are unaware of
any known mechanisms to explain this relationship. One
plausible explanation is that low blood cholesterol alone

or low dietary magnesium in combination with low blood
cholesterol may increase the risk of atrial fibrillation,36,37
the main risk factor for cardioembolic infarction. However, there is little evidence to support this possibility at
the present time.
Conclusions and Directions for Future Research
There have been few cohort studies on the relationshipbetween serum cholesterol levels and cardiovascular disease in Japan. One reason for this is the low incidence inJapan of CAD, which is associated strongly with hypercholesterolemia. As described in this article, the association between hypercholesterolemia and cerebral infraction is weak, making it difficult to perform epidemiologic
studies due to the need for large sample sizes to achievesufficient statistical power.
Furthermore, there are some residual issues to be clarified in the cohort studies in Japan. Some cohort studies inJapan have shown an inverse relationship between HDLC
and cerebral infarction or stroke.38,39 The Suita study
showed a positive relationship between serum triglycerides (TG) and cerebral infarction.40 However, none ofthese studies showed any association between TC (LDLC)
and the risk of cerebral infarction. From the viewpoint of
the “lipid hypothesis,” it is difficult to understand thesefindings. Because both HDLC and TG are strongly associated with metabolic syndrome and visceral fat accumulation, participants of cohort studies with abnormalities in these lipids may be affected by the new onset of
hypertension during follow-up, which may be related tothe incidence of stroke.41 However, most cohort studies
did not evaluate the longitudinal trend for each risk factor
after the baseline survey. Accordingly, we need further
research to address this concern.
The atherogenic effect of hypercholesterolemia is wellestablished and is based on evidence from numerous epidemiological, pathological, and biological studies. Furthermore, the proportion of atherothrombotic cerebral infarctions may have recently increased in Japan, because
this subtype currently accounts for approximately one
third of cerebral infarctions in the Japan Standard Stroke
Registry Study (JSSRS).42 We should formulate a confirmed strategy for lipid management to prevent cerebral
infarction. Toward this end, further long-term, prospective research needs to be undertaken to clarify the effectof blood cholesterol levels on stroke.
Acknowledgments
This research was supported by a Grant-in-Aid from
the Ministry of Health, Labor, and Welfare, Health andLabor Sciences Research Grants, Japan (Comprehensive
Research on Cardiovascular and Life-Style Related Diseases: H23-Junkankitou [Seishuu]-Ippan-005).

Keio J Med 2012; 61 (3): 79–88

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