Cardiovascular disease (CVD) prevention in Asia is an important issue for the world health because half of the world’s population is living in Asia. Asian countries and regions such as Japan, the Republic of Korea, the People’s Republic of China, Hong-Kong, Taiwan and the Kingdom of Thailand have the characteristic feature of higher stroke mortality and morbidity than of coronary heart disease (CHD), while Western countries have vice versa 1). The reasons why this specific characteristic is observed in countries with rapid and early phase westernization such as Japan and South Korea are very interesting.
It is well known that the Seven Countries Study conducted by Keys, Blackburn, Kimura, et al. in 1957 found that Japanese populations had lower fat intake, lower serum total cholesterol and lower CHD in spite of higher smoking rates compared to those of the United States and Scandinavian populations2). Serum total cholesterol level in Japan has increased rapidly after World War II following an increase in dietary fat intake from 10% of total energy intake per capita per day to 25% 1,2). Despite this increase, the specific characteristic of a lower CHD incidence and mortality than that of Western countries has continued to persist up to the present time3,4). Thus, it has been discussed for a long time whether or not Japanese people and some other Asian populations have different risk factors for CHD than Western populations.
In this article, we present features of higher stroke rates and lower CHD rates in Asian countries than in Western countries and their risk factors based on extensive reviews of cohort studies, and discuss whether or not those risk factors are different from those of Western countries. Along with this, we discussed the relationship between serum total cholesterol and total stroke and its subtypes. We also addressed the emerging problems and important issues for cardiovascular disease (CVD) prevention in Asia.
Extensive paper search for this review was mainly performed focusing on distinguished cohort studies and researchers’ names by country in Asia. For mortality data, statistics of the World Health Organization were obtained5).
I. Mortality and Morbidity of Stroke and Coronary Heart Disease
Mortality from Stroke and Coronary Heart Disease
The available data from the World Health Organization on age-adjusted mortality for men and women combined from cerebrovascular disease (stroke) and CHD are shown in Figure 1 5). The left panel of Figure 1 shows age-adjusted stroke mortality for some selected Asian countries with some Western countries, Australia, and New Zealand in 2002 for comparison. In general, stroke mortality in Asian countries except Japan and Singapore is higher than in Western countries. However, it is worth mentioning that Japan had the highest stroke mortality in the world in 1965. It rapidly decreased by about 80% during the year 1965–1990 1). The present stroke mortality in Japan has a similar level to those of Western countries. Interestingly, the stroke mortality trends in China and South Korea is now showing the similar characteristics of the Japanese trend observed in the past. The recent age-adjusted stroke mortality in China is reported to be decreasing in the urban area, while in the rural area mortality is still increasing or is being stable6). In South Korea, age-adjusted stroke mortality is also deceasing but still in the higher level. Other Asian countries, including Middle Eastern countries, Central Asian countries, and South Asian countries except Singapore also have higher stroke mortality than Western countries. Therefore, it can be concluded that Asian countries in general have higher stroke mortality than Western countries.
Figure 1.
Age-standardized death rates per 100,000 for stroke (the left panel) and coronary heart disease (the right panel) across countries of different regions of Asia in 2002. Available from the World Health Organization, Department of Measurement and Health Information. The patterns show by regions: Middle Eastern countries, Central Asian countries, South Asian countries and East Asian countries.
For age-adjusted CHD mortality, it is of interest that East Asian countries have lower mortality than the other Asian countries except for Thailand. As observed in the Seven Countries Study2), East Asian countries still retain the same characteristic of lower CHD mortality as observed in Mediterranean countries1,2). A large cohort study in China also confirmed that age-adjusted stroke mortality was 3 times higher than CHD mortality3). Therefore, it is a specific characteristic that East Asian countries have higher stroke mortality but lower CHD mortality than Western countries. Other Asian countries have higher CHD mortality as well as higher stroke mortality than East Asian countries as well as Western countries. It is worth noting that Central Asian countries which belonged to the past Soviet Union have both the highest age-adjusted stroke and CHD mortality followed by other Middle East Asian and South Asian countries among all Asian countries (Figure 1).
Incidence of Stroke and Myocardial Infarction
Data on age-adjusted incidence of stroke and myocardial infarction for men and women aged 35–64 in 1985–1987 is available from the World Health Organization (WHO) Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project7,8). Results of a Japanese registration data with the same diagnostic criteria is compared with the MONICA results in Figure 2 and 3. The Japanese data was surveyed during the year 1989–19931). Stroke incidence of 6 Japanese populations and one Chinese population are scattered in the middle levels (Figure 2), while the incidence of acute myocardial infarction (AMI) in China and 6 Japanese populations were far lower compared to the Western populations (Figure 3). In South Korea, it is also observed that stroke incidence is higher than myocardial infarction9). The specific characteristic is that East Asian countries including Japan have lower incidence and mortality from CHD than stroke.
Figure 2.
Age-adjusted (35–64 years) stroke incidence for a MONICA study in 1985–87 and a Japanese study in 1989–1993. The diagnostic criteria of the MONICA study were used for the Japanese study. Male stroke incidence (the left panel) for the six Japanese and one Chinese population in Beijing, China showed that the rates were in the middle of these populations and definitely lower than that of Finland. The female Beijing population belongs to the higher group (the right panel). The world standard population was used for the calculation of age-adjusted rates of 35–64 years old.
Source: Cited from the Reference 1. (By permission of Japan Atherosclerosis Society)
Figure 3.
Age-adjusted (35–64 years) incidence of acute myocardial infarction for a MONICA study in 1985–87 and a Japanese study in 1989–1993. The incidence rates of six Japanese populations and China were far lower than those of selected Western countries. The world standard population was used for the calculation of age-adjusted rates of 35–64 years old.
Source: Cited from the Reference 1. (By permission of Japan Atherosclerosis Society)
For addressing trends in mortality and incidence of CHD compared with stroke, diagnostic fashion and improved case findings may have an influence on the statistics in less developed countries. Even if it is the case, the specific characteristics in East Asian countries hold true.
II. Subtype of stroke
Stroke mortality and incidence are higher in East Asian countries than in Western counties. In addition to this, hemorrhagic stroke in East Asian countries was relatively higher than in Western countries. Approximately, the ratio of cerebral infarction to cerebral hemorrhage is 2–3:1 in East Asian countries, while it is 5–10:1 in Western countries (Online Supplement Table 1). But this feature has become weaker in recent years due to the decline in hemorrhagic stroke incidence and mortality1,10). In addition, it is worth mentioning that incidence of lacunar stroke is dominant in Japan11–13) among ischemic stroke incidence compared to large thromboembolic stroke incidence than in Western countries14,15). Lacunar stroke decreased by around 50% in Japan during 1961–2000 in the Hisayama study16) following blood pressure reduction and a decreasing smoking rate.
III. Risk factors for Stroke and CHD
Similar to the well established traditional risk factors for stroke1,17) and CHD1,2,4,18); hypertension, smoking, and diabetes mellitus (DM) are the main risk factors for stroke in Asia1,17). A large scale meta-analysis project named Asia Pacific Cohort Studies Collaboration (APCSC), which includes 44 separate cohorts (mainland China, Hong Kong, Taiwan, Japan, South Korea, Singapore, Thailand, New Zealand and Australia) and more than 650,000 individual data, showed that hypertension19), smoking20) and DM21) were major risk factors for fatal and non-fatal stroke. However, APCSC found that the slope of the relationship between blood pressure and fatal and non-fatal stroke was steeper in Asian countries than in Australia and New Zealand19). In addition, the slope of the relationship between systolic blood pressure (SBP) and hemorrhagic stroke was steeper than that of the relationship between SBP and ischemic stroke19).
Serum total cholesterol is a risk factor for CHD in Asian countries22,23). It is clearly shown in Asian cohort studies that serum total cholesterol level is positively related to CHD morbidity and mortality 22,23). However, serum total cholesterol is not a risk factor for total stroke17,24), although it was a weak risk factor for cerebral infarction22,25) and low cholesterol was rather a weak risk factor for cerebral hemorrhage24–27), especially in hypertensives24,25) based on observational cohort studies. On the other hand, a large individual based meta-analysis 28) showed that cholesterol lowering therapy with statins could prevent total stroke or ischemic stroke without increasing hemorrhagic stroke. This discrepancy should be studied further to clarify the reasons.
In Japan, lacunar stroke is more prevalent than large-artery atherothrombotic ischemic stroke11–13). The main risk factors for lacunar stroke are hypertension, smoking and DM13,14), although the Hisayama study showed that serum total cholesterol was also a risk factor for lacunar stroke13). On the other hand, large-artery atherothrombotic ischemic stroke may relate with serum total cholesterol. However, this remains to be investigated. There are no reports clearly showing a positive relationship between serum total cholesterol and atherothrombotic stroke in China and Korea.
Based on observational cohort studies, it is understood that serum total cholesterol is not a risk factor for total stroke and less important even for ischemic stroke in East Asian countries.
Smoking is a major risk factor for stroke (total, ischemic and subarachnoid strokes) and CHD even in Asian countries1,4,17,20,29,30) where CHD is generally lower than in Western countries except Singapore31). Smoking is not so clearly a risk factor for cerebral hemorrhage 20,29) as for subarachnoid hemorrhage and ischemic stroke30,32,33).
IV. Burden of Risk Factors for CVD in Asian Populations
Blood pressure and the prevalence of hypertension
Blood pressure and the prevalence of hypertension are higher in East Asia than in South Asia34). High quality standardization for blood pressure measurement is needed for the comparison of blood pressure level and also of the prevalence of hypertension across countries and/or populations35,36). International study of macro- and micro-nutrients and blood pressure (INTERMAP)36) and several other studies 37–41) found that blood pressure levels and the prevalence of hypertension in the northern part of China were higher than those in the southern part of China. The difference in blood pressure between the north and south populations is partly explained by the difference in salt consumption37–41). Relationship between salt consumption and blood pressure in individuals are reported from Japan35,36), China37–41) and Korea42).
Trends in blood pressure levels by the Japanese National Nutrition and Health Survey showed that it was highest in 1965 and substantially declined during the years 1965–1990 for men and women in all age groups; i.e., around 16 mmHg decline of SBP was recorded in men aged 60–69 years old1). Concomitantly, stroke mortality declined greatly by around 80% in Japan during 1965–19901). It is worth noting that salt consumption in the northern part of Japan was 26–27g/day, estimated by 24 hr urine collection in 1950s 43), and is now around 13g/day. Currently, well standardized epidemiologic studies show that Japanese populations have similar levels of blood pressure with Americans 35,36,44). An international co-operative study of electrolyte excretion and blood pressure (INTERSALT) and the INTERMAP studies show that salt consumption in northern Chinese populations is higher than those in Japanese populations35,36). The Korean population also has a higher salt consumption than the Japanese population35,42). Therefore, high salt and high blood pressure still continue in East Asian countries, although substantial reduction in salt consumption and blood pressure has been observed in Japan1).
APCSC reported that the population attributable fraction (PAF) of hypertension for CVD is up to 60% in Asian countries45). In addition, the total number with hypertension in China and India is expected to increase to >500 million by 202546). However, awareness of hypertension in Asia is less than 50% in Chinaand India46) (although not so in Japan), and these rates are far lower than Western countries. In addition, the treatment rate is lower in Asia, especially in low income countries 46). Therefore, we have to increase awareness of hypertension and implement all possible policies to reduce and prevent it. However, it is pointed out that there are several barriers to doing this: drug cost, the need for a primary healthcare system to identify high risk individuals, and policy barriers preventing implementation of programs to lower blood pressure 46).
High smoking rate
The smoking rate for men in Asian countries except Singapore, Hong Kong and India in 2000 is still high at 40–60 % 1,46–49), although that has reduced substantially over the last two decades (Figure 4) 48,50–54). On the other hand, the smoking rate for women in all Asian countries is far lower at 3–15%, than in Western countries1,46–49). It is a specific characteristic in Asia that women smoke and drink much less compared to men1,46–49).
Figure 4.
Trends in smoking rate by sex and by selected Asian countries. Smoking rate for women in Asian countries is similarly lower (less than 10%) than those for men. Among Asian countries, Singapore showed the lowest smoking rate for men and women, with a declining smoking rate for men. The smoking rate for men in Japan, Korea, China and Vietnam remains high: over 45%, although the declining trends in smoking rate are clear in men.
Data were obtained from the following References 48 and 50–54.
Since smoking is a potent risk factor not only for CHD but also for stroke, the PAF of smoking for CVD is high at 30% following high blood pressure45,49). The impact of smoking for PAF in men is much stronger than in women (13–27% VS 2–7% for men and women, heart disease) 49), although smoking is strongly related to the excess of cardiovascular mortality and morbidity in men and women49,55). The full impact of smoking on CVD may appear later years, because epidemic of smoking is a more recent phenomenon in China than other Asian countries, e.g., Japan (Fig. 4). In any cases, quitting smoking, especially in men, can greatly reduce CVD in Asia.
Increasing in serum total cholesterol
Serum total cholesterol levels in Asian countries are generally lower than in the United States of America (USA) and other Western countries2) (Figure 5). Among Asian countries, the serum total cholesterol level in Singapore in 1982–85 was highest. The age-adjusted CHD mortality in Singapore was also higher than the East Asian countries2,4). The higher serum total cholesterol level and age-adjusted mortality from CHD in Singapore has decreased in recent years4). Among most of the other Asian countries, serum total cholesterol has increased from around 4.1mmol/l (160 mg/dl) to 4.9mmol/l (190mg/dl) for middle aged men, and these levels are almost similar with those of the Japanese population in 1970–198056,57). These increases in serum total cholesterol level in Asian countries are well compatible with the increase in total and saturated fat intake1,56–58). It is recorded that total fat intake in the National Nutrition Survey of Singapore in 1998 was 31% of total energy intake, while that in Japan in 1998 was around 26%1,4). Accordingly, INTERMAP study in 1996–99 showed that the fat energy intake of Chinese populations for men aged 40–59 years old was 20%, for Japanese populations was 24%, for USA population was 34%, and for UK population was 33%36). The National Nutrition Survey in South Korea58) shows that average fat intake per capita per day was 19% of total energy intake, and this was lower than those of China and Japan.
Figure 5.
Serum total cholesterol levels for men among Asian populations in 1980–2000, and in the USA in 1960–91. The serum total cholesterol in Singapore was the highest among the selected Asian population, followed by Hong Kong and Japan. That of Japanese people increased from 1980–2000, and currently young people show levels similar to their American counterparts. However, there remains a 20mg/dl difference in those of the elderly Japanese and Americans. The levels of Taiwanese and Korean populations were between those of the Japanese and Chinese. Chinese and some Korean populations show lower serum total cholesterol levels than those of other industrialized Asian populations.
Source: Cited from the Reference 4. (By permission of Oxford University Press)
Prevalence of glucose intolerance and DM
Glucose intolerance and DM are risk factors for CHD and stroke in Asia as in Western countries17). However, Asian populations are presently less obese than Western populations; the body mass index (BMI, kg/m2) is around 20–24 in Asian but 26–29 in the West36,58). Since BMI in most of the Asian countries is increasing, the prevalence of glucose intolerance and DM may increase further. APCSC results show that the hazard ratios of DM to ischemic stroke and CHD are similar and around 2 for both Asian and Western countries21).
The prevalence of DM has been increasing throughout Asia and the speed of increase is much faster than in Western countries. The World Health Organization (WHO) estimated that of 171 million individuals with DM worldwide, more than 80 million live in Asia in 200059). The WHO projected these numbers will double by the year 2030 with the greatest increase in Asia. Therefore, we should carefully monitor obesity trends in Asia which cause DM, metabolic syndrome and/or risk factor clustering for CVD60).
Migrant studies on CVD, diabetes and atherosclerosis of Asian populations
Migrant studies of Asian populations to Western countries generally show increases in CHD, type 2 diabetes and atherosclerosis. Migrant studies of Japanese in the USA, e.g., the Honolulu Heart Program (HHP), show that Japanese Americans have higher CHD rates compared to the Japanese in Japan.61), while stroke rates in Japanese Americans are lower than those in the Japanese in Japan and Caucasians.62) Likewise, migrant studies of Asian Indians show the increase in CHD. Migrant Asian populations including Chinese, Indians, and Japanese, have higher prevalence of type 2 diabetes not only than their home countries but also than whites where Asians migrated.
A recent multi-ethnic study of 6,700 men and women in the USA show that the presence of coronary artery calcification (CAC) predicts future CHD similarly both in whites and Chinese Americans63), although the latter have lower prevalence and slower progression of CAC. In men in the post World War II birth cohort, Japanese Americans and whites have similarly high prevalence of CAC which is significantly higher than that in the Japanese in Japan. 64)
Conclusions
In Asian countries, stroke is more prominent than CHD. This is most likely due to a higher prevalence of hypertension and a lower level of serum total cholesterol in Asian countries. The PAF of hypertension for CVD is up to 60% in Asian countries. High blood pressure accompanies high salt intake in East Asia, while low serum total cholesterol accompanies lower fat intake. Reduction in salt consumption in East Asian countries, including Japan, is important for the reduction of CVD, especially for that of stroke. Prevention of smoking is also an important strategy for reducing CVD in most Asian countries, especially for men. The PAF of smoking for CVD is around 30%. Recent westernization in Asian countries is increasing fat consumption followed by the increase in serum total cholesterol. This may cause the increase in CHD in Asian countries. The prevalence of obese people is also increasing, and this may also increase the prevalence of DM, glucose intolerance and metabolic syndrome. These traditional risk factors management for CVD is important for the prevention of CVD in Asian countries as well as in Western countries.
Supplementary Material
Acknowledgments
It is pleasure to express appreciation to Ms Takako Mihara and Ms Chiaki Masuda for their clerical assistance.
Founding Sources
This research was supported by grants A 13307016 from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and R01 HL68200 and HL071561 from the National Institutes of Health.
Footnotes
Disclosures
Nothing
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