Circulation Journal

Official Journal of the Japanese Circulation Society

CARDIOVASCULAR EPIDEMIOLOGY IN ASIA
http://www. j-circ.or.jp

Epidemiology of Stroke and Coronary

Artery Disease in Asia
Jun Hata, MD, PhD; Yutaka Kiyohara, MD, PhD

Stroke and coronary artery disease (CAD) are major causes of death throughout the world. As half of the world’s
population lives in Asian countries, prevention of stroke and CAD in Asia is crucial. According to the vital statistics,
East Asian countries have a lower mortality rate for CAD than for stroke. In contrast, CAD is a more common cause
of death than stroke in other Asian countries and Western countries. Hypertension, diabetes, hypercholesterolemia,
and smoking are major risk factors for stroke and CAD in Asia as well as in Western countries. In an observational
study in Japan, the stroke incidence decreased as a result of improvements in blood pressure control and reduction
in the smoking rate over the past half century, whereas the CAD incidence did not show a clear secular change,
probably because the benefits of blood pressure control and smoking cessation were negated by increasing preva-
lence of both glucose intolerance and hypercholesterolemia. Although Asian populations have lower serum choles-
terol levels than Western populations, the prevalence of hypercholesterolemia has increased during the past half
century in Asia. In addition, the smoking rate among Asian men is higher than for Western men. These results un-
derscore that, in addition to blood pressure control, smoking cessation and the management of metabolic risk factors
are very important for prevention of stroke and CAD in Asia.   (Circ J 2013; 77: 1923 – 1932)

Key Words: Asia; Coronary artery disease; Epidemiology; Risk factors; Stroke

C
ardiovascular diseases (CVD), such as stroke and cor-
onary artery disease (CAD), are major causes of mor-
tality in both developed and developing countries in
the world. As half of the world’s population now lives in Asian
countries, prevention of CVD in Asia is a very important issue
for world health. The lifestyles and genetic backgrounds of
Asian populations differ from those of Western populations,
and therefore epidemiological evidence from Asian countries
is necessary to understand and to reduce the burden of CVD
in Asia.
In this review article, we first compare the mortality and
incidence rates of stroke and CAD across Asian and Western
countries. We also review observational studies that examined
secular trends in the incidence or mortality of CVD in Asian
populations. Next, we overview some prospective cohort stud-
ies that have examined the influence of major cardiovascular
risk factors, namely, hypertension, diabetes mellitus, hyper-
cholesterolemia, and smoking, on the risk of CVD in Asia.
The Burden of CVD in Asia
CVD Mortality and Incidence in Asia
Figure 1 shows the age-adjusted mortality rates of stroke and
CAD in 9 Asian countries (3 in East Asia, 3 in Southeast Asia,
and 3 in South Asia) and 3 Western countries for comparison
(the United States, the United Kingdom, and Australia), on the
basis of vital statistics data in 2002.1 With the exception of
Japan, the Asian countries had a higher stroke mortality than
the Western countries. Among the Asian countries, the stroke
mortality in Japan was the lowest and similar to that in Western
countries. On the other hand, the CAD mortality among Asian
countries showed a diverse pattern. In East Asian countries,
especially Japan and South Korea, CAD mortality was much
lower than in Western counties. In South Asian countries, the
mortality rates of stroke and CAD were much higher than in
Western countries. Although East Asian countries had higher
stroke mortality than CAD mortality, CAD mortality was more
common than stroke mortality in other Asian countries as well
as in Western countries.
The mortality data used for vital statistics are usually based
on death certificates recorded by physicians. However, the in-
formation on the death certificate is not always accurate2 and
not based on standardized criteria. Therefore, epidemiological
studies with standardized diagnostic criteria are more useful to
compare the incidence of CVD among countries. The WHO
Multinational Monitoring of Trends and Determinants in Car-
diovascular Disease (MONICA)3,4 is a well-performed epide-
miological project that examined the CVD incidence among
different countries, using uniform and standardized diagnostic
criteria. In that project, the age-adjusted incidence rates of
stroke3 and acute myocardial infarction (MI)4 were compared
among different populations aged 35–64 years. Figure 2 shows
the incidence rates of stroke and acute MI for men and women
in the MONICA populations and 6 Japanese populations using

Received June 19, 2013; accepted June 25, 2013; released online July 11, 2013
Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Mailing address:  Jun Hata, MD, PhD, Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University,
3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.   E-mail: junhata@envmed.med.kyushu-u.ac.jp
ISSN-1346-9843  doi: 10.1253/circj.CJ-13-0786
All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp

Circulation Journal  Vol.77, August 2013

1924
the same diagnostic criteria.5 The stroke incidence rates in the
Japanese and Chinese populations were scattered in the mid-
dle of the distribution chart. In other words, the East Asian
populations did not have higher stroke incidence than Western
populations. In contrast, the incidence rates of acute MI in
Japanese and Chinese were much lower than those in Western
populations.
Thus, East Asian countries have lower incidence and mortal-
ity rates of CAD than Western countries. These findings may
be related to the fact that the serum cholesterol levels in these
countries are lower than in Western countries.1,5,6
Secular Trends in CVD Incidence and Mortality
Although in recent years Japan has had the lowest mortality
rates of stroke among Asian countries, it is worth mentioning
that the stroke mortality in Japan based on vital statistics was
the highest in the world in the 1950 s to the 1960 s, and it
greatly decreased during the period from the 1970 s to the
1990 s.5,7 Several population-based observational studies in
Japan have evaluated the secular trends in the incidence of
stroke8–13 or CAD.9–11,14 One of these investigations, the
Hisayama Study,8 a population-based cohort study of CVD in
the town of Hisayama, Fukuoka, Japan, established 4 cohorts
consisting of residents aged ≥40 years without a history of
CVD in, respectively, 1961 (the first cohort, n=1,618), 1974
(the second cohort, n=2,038), 1988 (the third cohort, n=2,637),
and 2002 (the fourth cohort, n=3,123). The Table summarizes
the age-adjusted prevalence of cardiovascular risk factors at
the baseline examinations of the 4 cohorts in the Hisayama
Study.8 The prevalence of hypertension was stable in men and
decreased slightly in women over the study period from 1961
to 2002, whereas the proportion of individuals receiving anti-
hypertensive agents increased consistently with time in both
sexes. As a result, the age-adjusted mean levels of blood pres-
Circulation Journal  Vol.77, August 2013
HATA J et al.
Figure 1.  Age-adjusted mortality rates of
stroke and coronary artery disease in Asian
and Western countries in 2002.1
sure (BP) among hypertensive men and women decreased
significantly throughout the study period. However, even in
the recent examination in 2002, mean systolic BP (SBP) levels
in hypertensive men and women were higher than 140 mmHg,
suggesting that most hypertensive subjects did not achieve the
target BP levels recommended by the clinical guideline for
hypertension.15 Smoking rates in men and women showed a
significant downward trend over the study period. In contrast,
the prevalence of metabolic risk factors (ie, glucose intoler-
ance and hypercholesterolemia) increased greatly over the
study period in both sexes, probably because of the Western-
ization of dietary habits and physical inactivity as a result of
motorization. Figure 3 shows the age-adjusted incidence rates
of stroke and CAD among the first 3 cohorts of the Hisayama
Study, together with 12-year follow-up data for each cohort.9
The incidence of stroke decreased greatly, by 48% for men
and by 25% for women, from the first cohort (1961–1973) to
the second cohort (1974–1986), probably because of the im-
provement in BP control in hypertensive subjects and the re-
duction in the smoking rate. Among the stroke subtypes, isch-
emic stroke in both sexes and intracerebral hemorrhage in men
showed a similar pattern of decrease. However, the decreasing
trend in the stroke incidence slowed from the second cohort to
the third cohort (1988–2000) in both sexes and a possible
reason for this slowdown may have been the steep increase in
metabolic risk factors, which could have negated the benefi-
cial effects of the improvement of hypertension management
and smoking cessation. Another reason may have been that BP
control among hypertensive individuals was still not suffi-
cient, even at the latest examination. In contrast, the CAD
incidence did not change throughout the study periods in ei-
ther sex. Again, the increase in metabolic risk factors and in-
sufficient control of hypertension may have contributed to the
trend in the CAD incidence.
Stroke and CAD in Asia 1925

Figure 2.   Age-adjusted incidence of stroke (A) and acute myocardial infarction (MI) (B) by sex in the MONICA study in 1985–1987
(orange bars indicate the Western cohorts; green bar represents the Chinese cohort) and in Japanese cohorts in 1989–1992 (blue
bars), all of which consisted of subjects aged 35–64 years.5 FIN-KUO, Kuopio Province, Finland; FIN-NKA, North Karelia, Finland;
RUS-NOI, Novosibirsk Intervention, Russia; LTU-KAU, Kaunas, Lithuania; FIN-TUL, Turku/Loimaa, Finland; YUG-NOS, Novi Sad,
Yugoslavia; JPN-HOKKAIDO, Hokkaido, Japan; JPN-SHIGA, Shiga, Japan; CHN-BEI, Beijing, China; SWE-NSW, Northern Sweden,
Sweden; RUS-MOC, Moscow Control, Russia; JPN-AKITA, Akita, Japan; RUS-MOI, Moscow Intervention, Russia; JPN-OKINAWA,
Okinawa, Japan; DEN-GLO, Glostrup, Denmark; JPN-NAGANO, Nagano, Japan; GER-KMS, Karl-Marx-Stadt County, Germany;
GER-HAC, Halle County, Germany; POL-WAR, Warsaw, Poland; JPN-OSAKA, Osaka, Japan; SWE-GOT, Gothenburg, Sweden;
GER-RDM, Rest of DDR (East Germany)-MONICA; GER-RHN, Rhein-Neckar Region, Germany; ITA-FRI, Friuli, Italy; UNK-BEL,
Belfast, United Kingdom; CAN-HAL, Halifax County, Canada; ICE-ICE, Iceland; USA-STA, Stanford (California), United States; CZE-
CZE, Czech Republic; NEZ-AUC, Auckland, New Zealand; AUS-PER, Perth, Australia; BEL-GHE, Ghent, Belgium; GER-EGE, East
Germany; SWI-TIC, Ticino, Switzerland; FRA-LIL, Lille, France; SWI-VAF, Vaud/Fribourg, Switzerland; SPA-CAT, Catalonia, Spain.

Circulation Journal  Vol.77, August 2013

1926 HATA J et al.

Table. Age-Adjusted Prevalence or Mean of Cardiovascular Risk Factors Among 4 Baseline Examinations

of the Hisayama Study8
1961 1974 1988 2002 P for
(n=1,618) (n=2,038) (n=2,637) (n=3,123) trend
Men
  Hypertension, % 38.4 43.1 44.1 42.0 　0.25　　
   Antihypertensive agents, % 2.0 8.4 13.2 18.2 <0.001
   SBP in hypertensive men, mmHg 162 157 151 148 <0.001
   DBP in hypertensive men, mmHg 91 90 87 89 　0.011
   Glucose intolerance, % 11.6 14.1 39.3 54.5 <0.001
  Hypercholesterolemia, % 2.8 12.2 26.9 25.8 <0.001
   Current smoking, % 75.0 73.3 50.4 46.9 <0.001
Women
  Hypertension, % 35.9 40.1 35.1 31.3 <0.001
   Antihypertensive agents, % 2.1 7.4 13.4 16.6 <0.001
   SBP in hypertensive women, mmHg 163 161 154 149 <0.001
   DBP in hypertensive women, mmHg 88 87 83 86 <0.001
   Glucose intolerance, % 4.8 7.9 30.0 35.5 <0.001
  Hypercholesterolemia, % 6.6 19.9 41.6 41.6 <0.001
   Current smoking, % 16.6 10.2 6.9 8.5 <0.001
SBP, systolic blood pressure; DBP, diastolic blood pressure. Hypertension defined as SBP ≥140 mmHg or DBP
≥90 mmHg or current use of antihypertensive agents. Hypercholesterolemia defined as total cholesterol level
≥5.7 mmol/L.

Figure 3.   Age-adjusted incidence of stroke and coronary artery disease (A) and stroke subtypes (B) by sex among the 3 cohorts
of the Hisayama Study with a 12-year follow-up in each cohort.9 *P<0.05 vs. the first cohort (1961–1973); †P<0.05 vs. the second
cohort (1974–1986).

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Stroke and CAD in Asia 1927

Figure 4.   Multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of cardiovas-
cular disease according to blood pressure (BP) categories in Asian and Oceanic populations evaluated in the Asia Pacific Cohort
Studies Collaboration (APCSC).21 HRs were adjusted for age, total cholesterol, and smoking, and stratified by sex and study.
Normal BP was used as the reference group. The center of each solid box is plotted against the point estimate, and the horizontal
lines are drawn to the 95% CIs. Reprinted with permission from Wolters Kluwer Health. 21

A decreasing trend in the stroke incidence was also ob-
served by other population-based epidemiological studies in
Japan.10–13 On the other hand, the secular trend in CAD inci-
dence in Japan has tended to vary among studies.10,11,14 The
Adult Health Study,14 a population-based cohort study per-
formed in the cities of Hiroshima and Nagasaki, showed an
almost constant incidence of MI during the 26-year period
from 1958 to 1984. The Akita-Osaka Study10 demonstrated a
significant increase in the CAD incidence among middle-aged
men (aged 40–69 years) living in an urban area (Osaka) during
the period from 1964 to 2003. There were no clear secular
changes in the CAD incidence among urban women in Osaka
and among rural men and women in Akita. Another cohort
study in Osaka11 also showed an increasing trend in the CAD
incidence among middle-aged men (aged 40–59 years) during
the period from 1963 to 1994. To summarize: the stroke inci-
dence in Japan clearly decreased over the past half century,
but the CAD incidence did not decrease. For middle-aged men
in urban areas of Japan, CAD incidence may have increased
because of Westernization of the Japanese lifestyle.
In other Asian countries, there have been few studies on
CVD trends based on vital statistics.16–18 A study in China re-
ported that the stroke mortality (per 100,000 persons) in urban
areas decreased remarkably during the period from 1987 to
2001 (from 373.9 to 258.1 for men, from 302.9 to 179.5 for
women), but with little change in rural areas over the same
period (from 321.6 to 336.8 for men, from 249.7 to 227.5 for
women).16 This finding suggests that healthcare services are
less developed in rural areas than in urban areas in China. A
study in Taiwan showed that the mortality rate of stroke de-
creased during the period from 1974 to 1988 and the decline
was much more striking for hemorrhagic stroke than for
ischemic stroke.17 Another study in Taiwan18 reported that the
CAD mortality increased slowly from 1971 to 1992. During
that period, the levels of cigarette smoking, dietary fat intake
and body mass index, and the prevalence of both hypertension
and diabetes increased. However, a downward trend in the
CAD mortality was observed from 1992 to 2001, probably
attributable to improvements in acute cardiac care and medical
treatment for patients with CAD in Taiwan.
Risk Factors for CVD
Hypertension
It is well established that hypertension is a strong risk factor
for both stroke and CAD. In a systematic review of cross-
sectional studies,19 the age-adjusted prevalence rates of hyper-
tension among adult populations were 38.3% in Japan, 27.7%
in China, 23.7% in Taiwan, 21.7% in Thailand, 23.8% in
North India (urban), and 30.7% in West India (urban). The
prevalence of hypertension in Japan seems to be higher than
that in other Asian countries, but it is difficult to make an ac-
curate comparison because the methods for data collection and
BP measurement were not standardized among the studies
examining this issue. In any event, we may roughly conclude
that one-quarter or one-third of the adult population in Asia

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1928 HATA J et al.

Figure 5.   Multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of ischemic
stroke and coronary artery disease according to glucose tolerance status in Japanese men and women aged 40–79 years enrolled
in the Hisayama Study.30 HRs were adjusted for age, systolic blood pressure, ECG abnormalities (left ventricular hypertrophy or
ST depression), body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and
regular exercise. Normal glucose tolerance was used as the reference group. The center of each solid box is plotted against the
point estimate, and the horizontal lines are drawn to the 95% CIs.

has hypertension.
Hypertension is usually defined as BP ≥140/90 mmHg.15 In
addition, the Seventh Report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC7)15 in the United States defined prehy-
pertension as BP of 120–139/80–89 mmHg, based on the evi-
dence of a modest increase in CVD risk among individuals
with such BP levels. In Asia, prehypertension was shown to
be a predisposing factor for future hypertension,20 and further-
more, there have been several studies that have confirmed the
direct association between prehypertension and the risk of
CVD.21–26
The Asia Pacific Cohort Studies Collaboration (APCSC)27
is a large-scale meta-analysis of 44 cohort studies with ap-
proximately 600,000 participants from Asia (China, Hong
Kong, Taiwan, Japan, South Korea, Singapore, and Thailand)
and Oceania (Australia and New Zealand). The influence of
high BP on the development of stroke and CAD was evaluated
using the individual participant data of the APCSC, which had
a mean follow-up period of 7 years.21 In that study, BP catego-
ries were classified as normal (SBP <120 mmHg and diastolic
blood pressure [DBP] <80 mmHg), prehypertension (SBP
120–139 mmHg and/or DBP 80–89 mmHg), isolated diastolic
hypertension (SBP <140 mmHg and DBP ≥90 mmHg), isolated
systolic hypertension (SBP ≥140 mmHg and DBP <90 mmHg),
and systolic-diastolic hypertension (SBP ≥140 mmHg and DBP
≥90 mmHg). As shown in Figure 4, multivariable-adjusted
hazard ratios (HRs) (95% confidence intervals [CIs]) for the
development of total CVD were 1.41 (1.31–1.53) for prehyper-
tension, 1.81 (1.61–2.04) for isolated diastolic hypertension,
2.18 (2.00–2.37) for isolated systolic hypertension, and 3.42
(3.17–3.70) for systolic-diastolic hypertension, compared with
normal BP as a reference. In a separate analysis, the prehyper-
tensive and hypertensive states were also found to have a sig-
nificant influence on the development of certain CVD sub-
types, namely, ischemic stroke, hemorrhagic stroke, and CAD.
The influence of high BP was stronger for hemorrhagic stroke
than for ischemic stroke and CAD. These associations were
stronger in Asian populations than in Oceanic populations.
The Hisayama Study22 reported the association of BP level
with the incidence of CVD using a cohort established in 1988.
A total of 2,634 residents aged ≥40 years without a history
of CVD were followed up for 19 years. BP categories were
defined according to the JNC7 classification15 with a modifi-
cation: namely, normal BP (<120/80 mmHg), lower range of
prehypertension (120–129/80–84 mmHg), higher range of
prehypertension (130–139/85–89 mmHg), stage 1 hyperten-
sion (140–159/90–99 mmHg), and stage 2 hypertension (≥160/
100 mmHg). The incidence of CVD rose progressively with
increasing BP, and increased significantly from the lower range
of prehypertension. The multivariable-adjusted HRs (95% CIs)
were 1.58 (1.11–2.26) for lower range of prehypertension, 1.70
(1.18–2.44) for higher range of prehypertension, 1.93 (1.37–
2.72) for stage 1 hypertension, and 2.78 (1.93–4.01) for stage
2 hypertension, compared with normal BP as a reference, after
adjustment for potential confounding factors. Among the CVD

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Stroke and CAD in Asia 1929

Figure 6.   Multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of stroke sub-
types and myocardial infarction according to serum cholesterol levels in Korean men and women aged 30–64 years in the Korean
National Health System Prospective Cohort Study.37 Hazard ratios were adjusted for age, sex, body mass index, height, serum
glucose, hypertension, ethanol consumption, smoking, physical activity, monthly pay, and area of residence. Participants with
serum cholesterol <3.36 mmol/L were used as the reference group. The center of each solid box is plotted against the point esti-
mate, and the horizontal lines are drawn to the 95% CIs.

subtypes, the influence of high BP was stronger for hemor-
rhagic stroke than for ischemic stroke and CAD.
These findings suggest that not only hypertension but also
prehypertension is an important risk factor for CVD in Asian
populations. For subjects with prehypertension, lifestyle mod-
ifications such as low-salt diet, physical exercise, and smoking
cessation are recommended to reduce BP and to prevent future
development of CVD.
Diabetes Mellitus
According to nationally representative data,28 the prevalence of
diabetes was 2.6% in China, 3.1% in Mongolia, 4.3% in India,
5.1% in Taiwan, 6.4% in the Philippines, 6.9% in Malaysia,
8.2% in Singapore, 9.6% in Thailand, 9.7% in Hong Kong, and
10.5% in South Korea. In Japan, the National Health and
Nutrition Survey29 reported that the prevalence of diabetes
among participants aged from 40 to 74 years was 11.9% in
total (16.9% in men and 8.4% in women) in 2011. The
Hisayama Study8 in Japan reported that the prevalence of glu-
cose intolerance (using a 75 g oral glucose tolerance test
(OGTT) and including impaired fasting glycemia, impaired
glucose tolerance, and diabetes mellitus) among residents aged
≥40 years was 54.5% in men and 35.5% in women in 2002,
suggesting that more than half of adult men and one-third of
adult women have diabetes or prediabetes in Japan. The preva-
lence of glucose intolerance in this town increased greatly
during the past half century (Table).
In the Hisayama Study,30 a total of 2,421 Japanese partici-
pants who underwent the 75 g OGTT in 1988 were followed
up for 14 years to estimate the association between glucose
tolerance status and the development of CVD. In that study,
glucose tolerance status was determined by the WHO criteria
in 1998:31 namely, normal glucose tolerance (fasting plasma
glucose [FPG] <6.1 mmol/L and 2-h postload glucose [2 hPG]
<7.8 mmol/L), impaired fasting glycemia (FPG 6.1–6.9 mmol/L
and 2 hPG <7.8 mmol/L), impaired glucose tolerance (FPG
<7.0 mmol/L and 2 hPG 7.8–11.0 mmol/L), and diabetes (FPG
≥7.0 mmol/L and/or 2 hPG ≥11.0 mmol/L). As shown in
Figure 5, the risks of ischemic stroke in both sexes and CAD
in women were significantly higher in subjects with diabetes
than in those with normal glucose tolerance, even after adjust-
ment for other confounding factors. The risks of ischemic
stroke and CAD did not significantly increase in subjects of
either sex with impaired fasting glycemia or impaired glucose
tolerance.
In the APCSC,32 the association of diabetes with the risk of
CVD was evaluated (median 5.4 years of follow-up). In that
study, the diabetic status of individual participants was deter-
mined on the basis of a reported medical history of diabetes at
baseline. The HRs (95% CIs) associated with diabetes were
2.02 (1.57–2.59) for fatal stroke, 2.19 (1.81–2.66) for fatal
CAD, 2.09 (1.65–2.64) for total (fatal and nonfatal) stroke,
and 1.73 (1.34–2.22) for total CAD. For all outcomes, HRs
were similar in the Asian and Oceanic populations. In another

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1930 HATA J et al.

Figure 7.   Multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of stroke sub-
types and myocardial infarction according to smoking status in Korean men aged 30 to 64 years enrolled in the Korean National
Health System Prospective Cohort Study.43 HRs were adjusted for age, height, blood pressure, body mass index, total cholesterol,
hyperglycemia, alcohol consumption, regular exercise, income, and area of residence. Never smoking was used as the reference
group. The center of each solid box is plotted against the point estimate, and the horizontal lines are drawn to the 95% CIs.

study using the data from the APCSC,33 there was a positive
log-linear association between fasting glucose and the risk of
total stroke and CAD. For both outcomes, the association was
continuous down to at least 4.9 mmol/L, with no evidence of
a threshold level. Overall, a 1 mmol/L lower fasting glucose
level was associated with a 21% (95% CI 18–24%) lower risk
of total stroke and a 23% (19–27%) lower risk of total CAD.
The associations were similar between the Asian and Oceanic
populations. Removing those with diabetes at baseline did not
substantially affect the associations, suggesting that high fast-
ing blood glucose is an important determinant of CVD even in
nondiabetic subjects.
In summary, diabetes is an important risk factor for stroke
and CAD in Asian populations. The APCSC study suggests
that a higher blood glucose level is associated with an in-
creased risk of CVD even in subjects without diabetes, al-
though the Hisayama Study did not show an increased risk of
CVD among subjects with prediabetes (impaired fasting gly-
cemia or impaired glucose intolerance). Further accumulation
of evidence is needed to determine whether hyperglycemia
increases the risk of CVD among nondiabetic subjects.
Hypercholesterolemia
In Western countries, CAD is related to high serum choles-
terol levels, whereas in Asian countries, serum total choles-
terol levels are generally low and the CAD incidence is much
lower.1,5,6 However, together with the growing industrializa-
tion and urbanization in Asia, serum total cholesterol levels in
Asian countries have increased during the past 50 years.6 For
example, the Hisayama Study in Japan8 reported that the age-
adjusted prevalence of hypercholesterolemia (defined as total
cholesterol [TC] ≥5.7 mmol/L) increased from 2.8% to 25.8%
in men and from 6.6% to 41.6% in women during the period
from 1961 to 2002 (Table). The increase in serum cholesterol
levels in Asian countries may be associated with the increase
in dietary intake of fat.34–36
Many epidemiological studies in Asia have confirmed
the association of cholesterol with the risk of CVD.37–41 The
Korean National Health System Prospective Cohort Study37
reported that serum cholesterol was positively associated with
the development of ischemic stroke and MI, and inversely
associated with hemorrhagic stroke, using 11-year follow-
up data from 787,442 Korean men and women aged 30–64
years (Figure 6). Multivariable-adjusted HRs (95% CIs) per
1 mmol/L increase in cholesterol were 1.20 (1.16–1.24) for
ischemic stroke, 0.91 (0.87–0.95) for hemorrhagic stroke, and
1.48 (1.43–1.53) for MI. The APCSC study38 evaluated the
association of TC with the risk of CVD using the median 5.5-
year follow-up data. Overall, each 1 mmol/L higher level of
TC was associated with an increased risk of coronary death
(HR 1.35, 95% CI 1.26–1.44) and fatal or nonfatal ischemic
stroke (HR 1.25, 95% CI 1.13–1.40), and a decreased risk of
fatal hemorrhagic stroke (HR 0.80, 95% CI 0.70–0.92). The
Hisayama Study39 in Japan demonstrated that the risks of de-

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Stroke and CAD in Asia
veloping nonembolic brain infarction and CAD were elevated
in subjects with high levels of low-density lipoprotein choles-
terol, but no clear association was observed for the risk of
hemorrhagic stroke. The Japan Arteriosclerosis Longitudinal
Study-Existing Cohorts Combine40 reported that non-high-
density lipoprotein (non-HDL) cholesterol was a more reliable
predictor for the development of acute MI than TC, but neither
TC nor non-HDL cholesterol was associated with any stroke
subtype.
To summarize, hypercholesterolemia is generally a risk
factor for atherosclerotic diseases such as ischemic stroke and
MI in Asian populations. Because the prevalence of hypercho-
lesterolemia has increased in Asia during the past half century,
the management of serum cholesterol is important to prevent
atherosclerotic disease in the future.
Smoking
According to the WHO report,42 the smoking rate in Asian
men (approximately >40%) is much higher than that in West-
ern men (30–40%). In contrast, the smoking rate in Asian
women (<20%) is much lower than that in Western women
(20–40%).
Smoking is reported to be a risk factor for both stroke and
CAD. In the Korean National Health System Prospective Co-
hort Study,43 the association of smoking with the development
of CVD was assessed using a large-scale cohort consisting of
648,346 Korean men with a 10-year follow-up. As shown in
Figure 7, there were strong linear trends of increased risk of
ischemic stroke, subarachnoid hemorrhage, and MI with great-
er number of cigarettes smoked per day. However, smoking
was not associated with intracerebral hemorrhage. Similarly,
the Hisayama Study44 in Japan reported that smoking was a
significant risk factor for ischemic stroke, subarachnoid hem-
orrhage, and CAD, but not for intracerebral hemorrhage. The
Japan Public Health Center-based Prospective Study on Can-
cer and Cardiovascular Disease (JPHC) Study45 also reported
that smoking raised the risks of ischemic stroke and subarach-
noid hemorrhage. In the APCSC study,46 the association of
smoking with CVD was evaluated using the data from a me-
dian 6.8 years of follow-up. In that study, the HR (95% CI)
comparing current smokers with nonsmokers was 1.32 (1.24–
1.40) for stroke and 1.60 (1.49–1.72) for CAD. There was a
clear dose-response relationship between the number of ciga-
rettes smoked per day and both stroke and CAD. The HR
(95% CI) for ex-smokers compared with current smokers was
0.84 (0.76–0.92) for stroke and 0.71 (0.64–0.78) for CAD,
suggesting that quitting smoking has a clear benefit.
To summarize, smoking is a risk factor for CAD and stroke
(particularly ischemic stroke and subarachnoid hemorrhage)
in Asian populations. Because smoking rates in men in Asian
populations are much higher than those in men in Western
populations, smoking cessation is very important for the pre-
vention of CVD in Asia.
Conclusions
We reviewed the vital statistics and data from observational
studies in Asia in order to understand the burden of CVD and
the influence of risk factors. Asian populations are character-
ized by higher stroke mortality, and East Asian populations
have lower CAD mortality and incidence than Western popu-
lations. Hypertension, diabetes, hypercholesterolemia, and
smoking were common risk factors for CVD in Asian popula-
tions as well as in Western populations. The prevalence rates
of hypercholesterolemia in Asia have increased during the past
Circulation Journal  Vol.77, August 2013
1931
half century, and the smoking rates in Asian men are much
higher than those in Western men. Therefore, management of
metabolic risk factors and smoking cessation, as well as BP
control, are very important for the prevention of CVD in Asian
countries.
Acknowledgments
None.
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