REVIEW
Obesity as a risk factor for cerebrovascular diseaseKazuo Isozumi
Department of Neurology, Ashikaga Red Cross Hospital, Tochigi, Japan(Received for publication on August 5, 2003)

Abstract. Obesity is widely recognized as a risk factor for coronary artery disease, but opinion isdivided regarding whether it is an independent risk factor for cerebrovascular disease; even now there
is no common view. In this study, the review sought to focus on a prospective study, but since obesity
and non-obesity basically cannot be randomly assigned, randomized controlled trials (RCT) are nonexistent. Accordingly, a cohort study (a method of clinical study in which the obesity group is actively
followed up for comparison with the non-obesity group in regard to cerebrovascular disease) was
mainly conducted. For reference, retrospective case-control studies are also shown. As a result, mostepidemiological surveys on the relation between simple obesity and cerebrovascular disease denied any
relation. That is, obesity alone, determined only on the basis of height and weight as shown by BMI(body mass index), etc., cannot be an independent risk factor for cerebrovascular disease; obesity can
become a risk factor only when accompanied by hypertension, hyperlipidemia, impaired glucose tolerance, etc. Recently, however, most papers conclude that abdominal obesity is a risk factor for cerebral infarction, provided that there are no data conﬁrming that obesity is a risk factor for hemorrhagic
cerebrovascular disease (cerebral hemorrhage and subarachnoid hemorrhage). (Keio J Med 53 (1): 7–
11, March 2004)
Key words: obesity, cerebrovascular disease (CVD), risk factor, body mass index (BMI), waist-to-hip
circumference ratio (WHR)

rebral infarction. In their results they listed aging,hypertension, electrocardiographic high R wave and
ST-T change, atrial ﬁbrillation and albuminuria as signiﬁcant risk factors, but did not list obesity and hyperlipidemia as risk factors.
A study by Wilhelmsen2 selected 47–55 year-old
males at random and conducted a follow-up survey for11.8 years; he reported that obesity was not a signiﬁcantrisk factor for stroke, though it was a risk factor forcoronary artery disease, and that hypertension, smoking and stress were related to stroke.
Also, a follow-up survey of 19,327 inhabitants of
Copenhagen from 1976 through 1983 conducted byBoysen, et al.3 revealed that low annual income,smoking, hypertension, diabetes, hypercholesterolemia,
ischemic heart disease and atrial ﬁbrillation were related to stroke, and that obesity was not a signiﬁcantrisk factor for stroke.
Konuma4 examined the role played by obesity in,
and other risk factors for, asymptomatic cerebral infarction on MRI. Subjects comprised 75 obese hyper-

Introduction
Obesity is widely recognized as a risk factor for coronary artery disease, but opinion is divided regardingwhether it is an independent risk factor for cerebrovascular disease; even now there is no common view. In
this study, the review sought to focus on a prospective
study, but since obesity and non-obesity basically cannot be randomly assigned, randomized controlled trials(RCT) are nonexistent. Accordingly, a cohort study (amethod of clinical study in which the obesity groupis actively followed up for comparison with the nonobesity group in regard to cerebrovascular disease) was
mainly conducted. For reference, retrospective casecontrol studies are also shown.
Negative Epidemiological Survey
From 1977 through 1983, Tanaka, et al.1 prospectively studied inhabitants of Shibata City, Niigata Prefecture, who were above 39 years of age, regarding ce-

Reprint requests to: Dr. Kazuo Isozumi, Department of Neurology, Ashikaga Red Cross Hospital, Honjo 3-2100, Ashikaga City, Tochigi Prefecture 326-0808, Japan, e-mail: k.isozumi@ashikaga.jrc.or.jp
78Isozumi K: Obesity as a risk factor for CVD

tensives at high risk of cerebral infarction. Regarding
results for body mass index (BMI), the MRI-positiveand -negative groups had 24.2 G 3.1 (kg/m 2 ; n ¼ 38)
and 23.4 G 2.9 (kg/m 2 ; n ¼ 37), respectively; that is, nosigniﬁcant difference was observed. Meanwhile, theMRI-positive group had signiﬁcantly high total serum
cholesterol and triglyceride values, and signiﬁcantly low
HDL cholesterol value. On the basis of the above
results, the author concluded that hyperlipidemia andhypertension were risk factors for asymptomatic cerebral infarction, and that obesity in itself had no part.
Haapaniemi, et al.5 surveyed risk factors for cerebral
infarction in the working-age population, using 506 patients and 345 controls. They concluded that risk factors
for cerebral infarction for males were excessive drinking, hypertension, heart disease, smoking, diabetes andpast history of migraine; the risk factors for females
were excessive drinking, use of oral contraceptives andsmoking; obesity was not found to be a risk factor for
cerebral infarction in either sex.
Gillum, et al.6 conducted a cohort follow-up surveyof 3,652 females and 3,284 males from 1971–1975
through 1992, and reported that while white male BMI
showed a U-shaped stroke risk, for black females surprisingly the lowest BMI group showed the highest riskof stroke.
Positive Epidemiological Survey
Hubert, et al.7 analyzed the results of a 26-year
follow-up survey of 5,209 inhabitants of Framingham
with regard to cardiovascular disease, including stroke,
and reported that in females above all, obesity was anindependent risk factor for stroke.
Herman, et al.8 conducted a case-control study of the
inhabitants of Tilburg, Netherlands, from 1978 through1981. From an analysis of 132 stroke patients and 239
age- and sex-matched controls, they concluded that
hypertension, acute myocardial infarction, arrhythmia,
transient cerebral ischemic attack, lack of exercise inspare time, poor education and obesity were risk factors
for stroke.
Abbott, et al.9 for 22 years followed up 1,163 nonsmoking Hawaiian males who had no evident risk factors for stroke, including hypertension and diabetes,
and reported that the onset rate of thromboembolic
stroke conspicuously increased among those with highBMI. This rate was signiﬁcant even after adjustment forage, systolic blood pressure, blood glucose level, etc.
This study is characterized in that they sought to determine the inﬂuence of obesity over a long period of time,
excluding individuals with other risk factors, such as
smoking. While smoking is a risk factor for stroke, it
decreases body weight; it is therefore better not to deal
with both factors at the same time.

Shinton10 conducted a case-control study on lifestylewith 125 stroke patients and 198 healthy persons in
Birmingham, and concluded that smoking, lack of exercise and obesity (BMI > 25 kg/m 2 ) were the risk factors for stroke, and that 79% of those cases could havebeen prevented if all three factors had been avoided.
Each of the 125 stroke patients had at least one of thethree risk factors.
Starting in 1976, Rexrode, et al.11 conducted a prospective cohort study of 116,759 American nurses, withthe aim of examining the relation between BMI andrisk of stroke in women. During 16 years, 866 nurses
suffered a stroke; of those, 403 had cerebral infarctionand 269 had cerebral hemorrhage. As to the relation
with BMI, at 27 kg/m 2 or more the risk of cerebral
infarction was signiﬁcantly high. Meanwhile, no relation
was observed between cerebral hemorrhage and BMI.
In the study, surveyed patients were limited to nurses,
but it seems highly reliable in that more than 100,000
nurses were followed up for 16 years.
In a study12 at Hisayama Town involving a typicalepidemiological survey in Japan, from 1961 through1996 change over time in risk factors for cerebral infarction was examined. The results showed that frequency of hypertension, the most signiﬁcant risk factor
for stroke, hardly changed for either sex. Meanwhile,
the rate of those who take depressors among hypertensives increased during the period, and the mean bloodpressure of hypertensives decreased sharply. On theother hand, over time the frequency of obesity and impaired glucose tolerance doubled or tripled, and thefrequency of hypercholesterolemia increased sharply,
to six to ten times. Though obesity was not analyzed
as an independent risk factor, the study concluded that
correction of obesity, lipid metabolic disorder and impaired glucose tolerance, as well as hypertension, is an
important task for the future.
Difference in Obesity Judgment Criteria
Though this is a known fact, it is given here for reference: BMI (kg/m 2 ) ¼ body weight (kg) o (height(m)  height (m)). In the United States, 25 kg/m 2 isdeﬁned as the standard and 30 kg/m 2 and upward isdeﬁned as obesity, but in Japan 22 kg/m 2 is deﬁned as
the standard (Japan Society for the Study of Obesity;1999), and obesity is deﬁned as beginning from BMI: 25(Table 1). In short, while in Western countries obesity
is considered normal, in Asia slimness is normal. Sinceeven the deﬁnition of obesity is quite different, interpretation of the literature, etc. requires caution. However, since it is known that Japanese more frequently
suffer from complications even when their obesity ismore modest than that of Western people, and since
Asian people are said to be less resistant to obesity than

Keio J Med 2004; 53 (1): 7–11
Table 1

9

Obesity Criteria

JASSO (1999)

BMI

WHO (1998)

Underweight
Normal range
Obese class 1
Obese class 2
Obese class 3
Obese class 4<18.5
18.5e @ <25
25e @ <30
30e @ <3535e @ <4040e

Underweight
Normal range
Preobese
Obese class I
Obese class II
Obese class III

JASSO: Japan Society for the Study of Obesity.

Western people, comparison in terms of BMI alone will
not be useful. Body fat performs the function of energy
storage, and the body fat of an ordinary person accounts for some 18% of body weight. If body fat goes
above 25% in a male and above 30% in a female, that
person is generally considered obese. While there arevarious methods of measuring stored body fat, no present methods can be called perfect in terms of price,
difﬁculty, precision, etc. Accordingly, in 1998, when the
WHO and the International Association for the Studyof Obesity adopted obesity determination using BMI,
one of physical constitution indexes, it was a turning
point; the Japan Society for the Study of Obesity thenalso adopted the method (Table 1).
Fat Sleep Apnea Syndrome andCerebrovascular Disease
Snoring, obstructive sleep apnea (OSA), daytime
sleepiness and obesity are recently attracting attention
as risk factors for cerebrovascular disease.
Palomaki13 conducted a case-control study using 177
male cerebral infarction patients and age-matched controls. As a result, he reported that snoring as well as
hypertension, ischemic heart disease and excessive alcohol consumption (300 g/week or more) was a signiﬁcant risk factor for ischemic cerebrovascular disease,and that OSA due to obesity would be the cause.
Shepard14 also reported that in habitually snoring
men the risks of ischemic heart disease, stroke andsudden death during sleep were heightened.
Neau, et al.15 conducted a case-control study of therelation between habitual snoring and cerebral infarction in 133 patients and 133 age- and sex-matchedhealthy persons. Results showed that the rate of habitually snoring persons was 23.3% for the cerebral
infarction group and 8.3% for the control group, a signiﬁcant difference (p < 0.001). In invariably snoring
aged male hypertensives, the risk of cerebral infarction
was especially high. As a result, the researchers maintained that in treating aged male hypertensives it was
important always to inquire about habitual snoring, so
as to prevent the onset of cerebral infarction.

Pressman, et al.16 reported two cases in which OSA
was the cause of transient ischemic attack (TIA). In
both cases, symptoms abated with continuous nasal
positive airway pressure. The relation between sleep
apnea and cerebrovascular disease has been shown not
only in statistical surveys but in real cases as well. Also,
they emphasized that in TIA cases caused by OSA,
early diagnosis and speciﬁc remedies were importantfor preventing recurrence.
Rangemark, et al.17 compared platelet function andﬁbrinolytic activity between 13 OSA cases and 10 sexand weight-matched controls. Results showed thatplasminogen activator inhibitor type 1 (PAI-1) value
was 18.4 G 3.6 IU/ml in OSA cases and 8.2 G 1.7 IU/ml
in controls, a signiﬁcant difference (p < 0.029). This result suggested decreased ﬁbrinolytic activity in OSA
cases. Although in this study the number of cases was
small, the data are notable in showing the mechanism of
myocardial and cerebral infarction increase in OSA
cases.
Abnormal Body Fat Distribution (Visceral Obesity)
and Cerebrovascular Disease
In recent years, body fat distribution has become asubject of discussion; abdominal fat in particular isindicated as becoming a risk factor for cardiovasculardisease. Abdominal obesity is expressed by waist-to-hip
circumference ratio (WHR) (waist size at navelomaximum hip size). Abdominal obesity is similar to visceralfat obesity. This type of obesity exhibits in many cases
multi-risk syndrome, which has been referred to as
syndrome X, deadly quartet, etc., accompanied by hypertension, diabetes and hyperlipidemia, based on insulin resistance.
For 18.5 years, Welin, et al.18 conducted a follow-up
survey of 789 54-year-old males; 57 (7.2%) of themsuffered stroke. Those researchers reported that hypertension, waist size (abdominal obesity), WHR, highserum ﬁbrinogen level, low lung capacity and maternal stroke were signiﬁcant risk factors, while BMI, serum cholesterol level, hematocrit, blood glucose level,smoking, ischemic heart disease, left ventricular hypertrophy and paternal stroke were not risk factors.
A two-year follow-up survey of 41,837 white femalesin Iowa conducted by Folsom, et al.19 showed signiﬁcantly numerous onsets of hypertension in the high
WHR group, high WHR being an independent risk
factor even with adjustment for other risk factors. Although there were also signiﬁcantly numerous onsets ofstroke in the high WHR group, high WHR became insigniﬁcant after adjustment for other risk factors. On
the basis of these results, the researchers presumed thathigh frequency of stroke onset in abdominal obesity
was mainly accompanied by diabetes and hypertension.

10
Table 2Isozumi K: Obesity as a risk factor for CVD
Abstract Table (Obesity as a risk factor for CVD)

AuthorTanaka, et al.
Wilhelmsen
Boysen, et al.
KonumaHaapaniemi, et al.
Gillum, et al.
Hubert, et al.
Herman, et al.
Abbott, et al.
ShintonRexrode, et al.
Fujishima
Palomaki
ShepardNeau, et al.
Pressman, et al.
Rangemark, et al.
Welin, et al.
Folsom, et al.
Walker, et al.
Bogousslavsky, et al.
Salonen, et al.
Handa, et al.
Nagatsuka

Reference No.

Published Year

Study Design

Result

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24

1985
1987
1988
1994
1997
2001
1983
1983
1994
1997
1997
1999
1991
1992
1995
1995
1995
1987
1990
1996
1985
1988
1990
1995

prospective
prospective
prospective
retrospective
retrospective
prospective
prospective
retrospective
prospective
retrospective
prospective
prospective
retrospective
retrospective
retrospective
case reportin vitro
prospective
prospective
prospective
retrospective
retrospective
retrospective
retrospective

negative
negative
negative
negative
negativepartly negative
partly positive
positive
positive
positive
positiveprobably positive
probably positive
probably positive
probably positive
probably positive
probably positive
partly positive
partly positive
partly positive
positive
negative
negative
negative

However, as a result of examining the correlation between BMI and WHR, they reported that WHR or abdominal obesity was more closely related to stroke onset than was BMI or general obesity.
Walker, et al.20 conducted a follow-up survey of
28,643 health care professionals in the United Stateswith regard to BMI, WHR and the stroke onset rate, todetermine whether abdominal obesity was a risk factor
for stroke, while recognizing that there was little evidence to conﬁrm that general obesity was a risk factor
for stroke. During a 5-year survey period, 118 persons
suffered stroke, 80 of whom suffered cerebral infarction. While BMI was not a risk factor, high WHR value
was a signiﬁcant risk factor. However, waist size in itself
was not a signiﬁcant risk factor.
Obesity and Carotid Lesions
Since any carotid lesion is, as a matter of course, arisk factor for cerebral infarction, the relation between
obesity and carotid lesion is the relation between obesity and cerebrovascular disease.
Bogousslavsky, et al.21 conducted a case-control
study of 159 patients with internal carotid artery stenosis and occlusion as diagnosed by angiography; as risk
factors they listed smoking, family history of stroke,ischemic ECG change, obesity, hypertension and hyperglycemia.
Salonen, et al.22 conducted ultrasonic carotid examination of 412 healthy male inhabitants of eastern Finland, and observed arteriosclerotic carotid lesions in
49% of them. As risk factors, they listed high LDLcholesterol value and low HDL cholesterol value, but
obesity was not listed.
Handa, et al.23 conducted ultrasonic carotid examination of 232 patients and quantitatively evaluatedthem by scoring arteriosclerotic lesions. As a result,they listed advanced age, male gender, hyperlipidemia
and diabetes as risk factors, but hypertension and obesity were not listed.
Nagatsuka24 analyzed the results of routine ultrasonic cervical examinations conducted in a physiological function test room on 383 persons from 50 to 80
years of age. Results showed that 66.9% of them had
cerebrovascular disease, and hypertension, diabetes
and hyperlipidemia were observed in 57.0%, 21.6% and48.1% of them, respectively. However, no signiﬁcantrelation was observed between obesity and carotid arteriosclerosis.
As indicated above, regarding the relation between
obesity and carotid lesions, negative opinions seem topredominate thus far.

Keio J Med 2004; 53 (1): 7–11

Conclusion
Most epidemiological surveys on the relationshipbetween simple obesity and cerebrovascular disease
deny any relationship. That is, obesity alone, determined only on the basis of height and weight as shown
by BMI, etc., cannot be an independent risk factor for
cerebrovascular disease; obesity can become a risk factor only when accompanied by hypertension, hyperlipidemia, impaired glucose tolerance, etc (Table 2).
Recently, however, most papers conclude that abdominal obesity is a risk factor for cerebral infarction, provided that there are no data conﬁrming that obesity is
a risk factor for hemorrhagic cerebrovascular disease(cerebral hemorrhage and subarachnoid hemorrhage).

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