Asia Pacific Cohort Studies Collaboration Research Articles

Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

SummaryBackgroundSeveral studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men.MethodsIn our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes.ResultsIndividual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97–2·24) and tripled risk among women (3·00, 2·71–3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35–59 years: 2·60, 2·30–2·94) than in older individuals (aged 70–89 years: 2·01, 1·85–2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35–59 years had the highest death RR across all age and sex groups (5·55, 4·15–7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35–59 years, the excess absolute risk was 0·05% (95% CI 0·03–0·07) per year in women compared with 0·08% (0·05–0·10) per year in men; the corresponding excess at ages 70–89 years was 1·08% (0·84–1·32) per year in women and 0·91% (0·77–1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes.InterpretationIndependent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained.FundingUK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health).

Clustering of risk factors and the risk of incident cardiovascular disease in Asian and Caucasian populations: results from the Asia Pacific Cohort Studies Collaboration

ObjectiveTo assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster.SettingAsia Pacific...

Consensus Document on Improving Hypertension Management in Asian Patients, Taking Into Account Asian Characteristics.

Hypertension is the major cause of mortality and the leading cause of cardiovascular disease worldwide. Blood pressure (BP) lowering either by lifestyle modification or medication leads to a reduction in cardiovascular events. However, there are significant ethnic differences in the determinants of hypertension and in the risk of hypertension-related demographics of cardiovascular disease.1–4 In Asian countries, stroke, especially hemorrhagic stroke, and nonischemic heart failure (HF) are more common than in Western countries. Stroke and HF are more closely related to hypertension than coronary artery disease or renal disease. In addition, data from the Asia Pacific Cohort Studies Collaboration show that the association between BP and cardiovascular disease is stronger in Asian patients than in white patients from Australia and New Zealand.5,6 In terms of the characteristics of determinants of hypertension, Asians are more likely to have higher salt sensitivity and salt intake than Western populations. Genetically, Asians are likely to have factors relating to salt-sensitive gene polymorphism of the renin–angiotensin system (RAS).7 In fact, Japanese people are more likely to develop pre-hypertension and hypertension even with a small increase in body mass index, and the body mass index associated with pre-hypertension was lower than that in Western countries.8 A previous survey of senior doctors in Asia demonstrated a need for Asian guidelines that take into account Asian characteristics of cardiovascular disease.9 Here, we have developed a consensus document for more optimal management of hypertension in East Asian people, which takes into consideration ethnic-specific characteristics. ### Consensus Statements 1. Stroke, especially hemorrhagic stroke, and nonischemic HF are common outcomes of hypertension-related cardiovascular disease in Asia. 2. The association between BP and cardiovascular disease is stronger in Asia than in the West. 3. Higher salt sensitivity, even with mild obesity and higher salt intake, is an Asian characteristic of …

The impact of body mass index on the associations of lipids with the risk of coronary heart disease in the Asia Pacific region.

Objective: To assess whether body mass index (BMI) modifies the associations of lipids with coronary heart disease (CHD).Methods: In the Asia Pacific Cohort Studies Collaboration, total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and triglycerides (TG) were measured for 333,297, 71,777 and 84,015 participants, respectively. All participants had measured BMI, categorized into underweight, normal, high-normal, overweight and obese, using standard definitions. For each BMI subgroup the effects of lipids on CHD were estimated per 1 standard deviation (SD) increase using Cox proportional hazard models, stratified by study and sex, adjusted for age and smoking. They were compared across the BMI groups, testing for interactions.Results: In the analyses for TC, HDLC and TG, there were 3121, 714 and 808 CHD events during a mean follow-up of 6.7 years. The risk of CHD increased monotonically with increasing TC and decreasing HDLC in all BMI subgroups without evidence of heterogeneity (p for interaction > 0.4). In contrast, the hazard ratio for CHD for a one SD increase in log-transformed TG increased from 1.07 (95%CI 0.72–1.59) in underweight, 1.26 (1.10–1.44) in normal weight, 1.27 (1.08–1.49) in high-normal weight, 1.37 (1.22–1.55) in overweight, to 1.61(1.30–1.99) in obesity (p = 0.01 for interaction trend). These associations were attenuated (p = 0.07 for interaction) but remained significant in the overweight and obese after further adjustment for TC and HDLC.Conclusions: Greater excess body weight exacerbated the effects of TG, but not TC or HDLC, on CHD, suggesting that additional effort is required to reduce TG in the overweight and obese.

Socioeconomic status in relation to cardiovascular disease and cause-specific mortality: a comparison of Asian and Australasian populations in a pooled analysis

ObjectivesIn Western countries, lower socioeconomic status is associated with a higher risk of cardiovascular disease (CVD) and premature mortality. These associations may plausibly differ in Asian populations, but data are...

A comparison of risk factors for mortality from heart failure in Asian and non-Asian populations: an overview of individual participant data from 32 prospective cohorts from the Asia-Pacific Region.

BackgroundMost of what is known regarding the epidemiology of mortality from heart failure (HF) comes from studies within Western populations with few data available from the Asia-Pacific region where the burden of heart failure is increasing.MethodsIndividual level data from 543694 (85% Asian; 36% female) participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality from HF were estimated separately for Asians and non-Asians for a quintet of cardiovascular risk factors: systolic blood pressure, diabetes, body mass index, cigarette smoking and total cholesterol. All analyses were stratified by sex and study.ResultsDuring 3,793,229 person years of follow-up there were 614 HF deaths (80% Asian). The positive associations between elevated blood pressure, obesity, and cigarette smoking were consistent for Asians and non-Asians. There was evidence to indicate that diabetes was a weaker risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95% CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction = 0.022. Additional adjustment for covariates did not materially change the overall associations. There was no good evidence to indicate that total cholesterol was a risk factor for HF mortality in either population.ConclusionsMost traditional cardiovascular risk factors including elevated blood pressure, obesity and cigarette smoking appear to operate similarly to increase the risk of death from HF in Asians and non-Asians populations alike.

A Comparative Analysis of Risk Factors and Stroke Risk for Asian and Non-Asian Men: The Asia Pacific Cohort Studies Collaboration

The risk of stroke is high in men among both Asian and non-Asian populations, despite differences in risk factor profiles; whether risk factors act similarly in these populations is unknown. To study the associations between five major risk factors and stroke risk, comparing Asian with non-Asian men. We obtained data from the Asia Pacific Cohort Studies Collaboration, a pooled analysis of individual participant data from 44 studies involving 386 411 men with 9·4 years follow-up. Using cohorts from Asia and Australia/New Zealand Cox models were fitted to estimate risk factor associations for ischemic and haemorrhagic stroke. We identified significant, positive associations between all five risk factors and risk of ischemic stroke. The associations between body mass index, smoking, and diabetes with ischemic stroke were comparable for men from Asia and Australia/New Zealand. The association between systolic blood pressure and ischemic stroke was stronger for Asian than Australia/New Zealand cohorts, whereas the reverse was true for total cholesterol. For haemorrhagic stroke, only systolic blood pressure and smoking were associated with increased risk, although the relationship with systolic blood pressure was significantly stronger for men from Asia than Australia/New Zealand (P interaction = 0·03), whereas the reverse was true for smoking (P interaction = 0·001). There was an inverse trend of total cholesterol with haemorrhagic stroke, significant only for Asian men. Men from the Asia-Pacific region share common risk factors for stroke. Strategies aimed at lowering population levels of systolic blood pressure, total cholesterol, body mass index, smoking, and diabetes are likely to be beneficial in reducing stroke risk, particularly for ischemic stroke, across the region.

Sex disparities in risk and risk factors for ischemic heart disease in the Asia-Pacific region

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide, with higher rates among men than women. Relatively few studies on risk factor associations are available from the Asia-Pacific region, especially with regard to sex differences. Our objective was to compare the relationships between modifiable risk factors and IHD in men and women from the Asia-Pacific region. Data from 600,445 individuals from 44 studies from the Asia Pacific Cohort Studies Collaboration, an individual patient data overview, were used. Cox models were used to evaluate the effects of risk factors on fatal and non-fatal IHD separately in men and women from Australia and New Zealand (ANZ) and Asia. Over a median follow-up of 6.7 years, 5695 IHD events were documented. The hazard ratio for IHD, comparing men with women, was 2.14 (95% CI 1.97-2.33) in ANZ and 1.88 (95% CI 1.54-2.29) in Asia. The age-adjusted prevalence of major risk factors was generally higher in men than women, especially in ANZ. Risk factors acted broadly similarly between men and women in both Asia and ANZ, with any indications of differences tending to favor men, rather than women. The excess risk of IHD observed in men compared with women in both Asia and ANZ may be, at least in part, a result of a more hazardous risk profile in men compared with women. The contribution of sex differences in the magnitude of the risk factor-disease associations is unlikely to be a contributing factor.

Behavioural and Metabolic Risk Factors for Mortality from Colon and Rectum Cancer: Analysis of Data from the Asia-Pacific Cohort Studies Collaboration

Colorectal cancer has several modifiable behavioural risk factors but their relationship to the risk of colon and rectum cancer separately and between countries with high and low incidence is not clear. Data from participants in the Asia Pacific Cohort Studies Collaboration (APCSC) were used to estimate mortality from colon (International Classification of Diseases, revision 9 (ICD-9) 153, ICD-10 C18) and rectum (ICD-9 154, ICD-10 C19-20) cancers. Data on age, body mass index (BMI), serum cholesterol, height, smoking, physical activity, alcohol and diabetes mellitus were entered into Cox proportional hazards models. 600,427 adults contributed 4,281,239 person-years follow-up. The mean ages (SD) for Asian and Australia/New Zealand cohorts were 44.0 (9.5) and 53.4 (14.5) years, respectively. 455 colon and 158 rectum cancer deaths were observed. Increasing age, BMI and attained adult height were associated with increased hazards of death from colorectal cancer, and physical activity was associated with a reduced hazard. After multiple adjustment, any physical activity was associated with a 28% lower hazard of colon cancer mortality (HR 0.72, 95%CI 0.53-0.96) and lower rectum cancer mortality (HR 0.75, 95%CI 0.45-1.27). A 2cm increase in height increased colon and all colorectal cancer mortality by 7% and 6% respectively. Physical inactivity and greater BMI are modifiable risk factors for colon cancer in both Western and Asian populations. Further efforts are needed to promote physical activity and reduce obesity while biological research is needed to understand the mechanisms by which they act to cause cancer mortality.

Effects of Prehypertension and Hypertension Subtype on Cardiovascular Disease in the Asia-Pacific Region

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure defined blood pressure (BP) levels of 120 to 139/80 to 89 mm Hg as prehypertension and those of ≥ 140/90 mm Hg as hypertension. Hypertension can be divided into 3 categories, isolated diastolic (IDH; systolic BP <140 mm Hg and diastolic BP ≥ 90 mmHg), isolated systolic (systolic BP ≥ 140 mm Hg and diastolic BP <90 mmHg), and systolic-diastolic hypertension (systolic BP ≥ 140 mm Hg and diastolic BP ≥ 90 mmHg). Although there is clear evidence that isolated systolic hypertension and systolic-diastolic hypertension increase the risks of future vascular events, there remains uncertainty about the effects of IDH. The objective was to determine the effects of prehypertension and hypertension subtypes (IDH, isolated systolic hypertension, and systolic-diastolic hypertension) on the risks of cardiovascular disease (CVD) in the Asia-Pacific Region. The Asia Pacific Cohort Studies Collaboration is an individual participant data overview of cohort studies in the region. This analysis included a total of 346570 participants from 36 cohort studies. Outcomes were fatal and nonfatal CVD. The relationship between BP categories and CVD was explored using a Cox proportional hazards model adjusted for age, cholesterol, and smoking and stratified by sex and study. Compared with normal BP (<120/80 mmHg), hazard ratios (95% CIs) for CVD were 1.41 (1.31-1.53) for prehypertension, 1.81 (1.61-2.04) for IDH, 2.18 (2.00-2.37) for isolated systolic hypertension, and 3.42 (3.17-3.70) for systolic-diastolic hypertension. Separately significant effects of prehypertension and hypertension subtypes were also observed for coronary heart disease, ischemic stroke, and hemorrhagic stroke. In the Asia-Pacific region, prehypertension and all hypertension subtypes, including IDH, thus clearly predicted increased risks of CVD.

Diabetes, body mass index and the excess risk of coronary heart disease, ischemic and hemorrhagic stroke in the Asia Pacific Cohort Studies Collaboration

ObjectiveTo examine the effects of diabetes on coronary heart disease, ischemic and hemorrhagic stroke and cardiovascular disease according to category of body mass index. MethodsData on 161,161 men and women from 31 cohorts (baseline years, 1966–99; mean follow-up, 2–24years) from the Asia Pacific Cohort Studies Collaboration were analyzed using Cox regression, stratified by sex and study and adjusted for age, systolic blood pressure and smoking. Diabetes was self-reported in all but one study. Body mass index was divided into five categories according to the World Health Organization Asian criteria. ResultsThe hazard ratio (diabetes v. not) for cardiovascular disease was 1.83 (95% confidence interval, 1.66–2.01). Across body mass index categories, this hazard ratio did not change significantly (p=0.19). Similar lack of difference across body mass index groups was found for coronary heart disease (p=0.33), ischemic stroke (p=0.97) and hemorrhagic stroke (p=0.98). ConclusionsBody mass index does not modify the effect of diabetes on major cardiovascular outcomes.

P2-309 Impact of excess weight on the relationship between blood pressure and cardiovascular disease: the Asia Pacific Cohort Studies Collaboration

BackgroundElevated blood pressure and excess weight are established major risk factors for cardiovascular disease (CVD). Previous studies have suggested that hypertension is a greater cardiovascular hazard among obese compared with...

The population attributable fraction of stroke associated with high blood pressure in the Middle East and North Africa

Hypertension and the prevalence of stroke are increasing in the Middle East and North Africa. This study aims to quantify the contribution of hypertension to the development of stroke at the country-level by calculating the sex-specific population attributable fraction (PAFs). The most recent sex-specific prevalence data was used, along with age-adjusted hazard ratio (HR) estimates for ischemic and hemorrhagic stroke associated with hypertension from the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence data were then used to calculate the PAFs for each country in the region with the relevant data. In the 10 countries with nationally-representative data, the PAFs in men ranged from 16.3% in Kuwait to 60.7% in Morocco for hemorrhagic stroke and 7.2% in Kuwait to 38% in Morocco for ischemic stroke. The equivalent PAFs for stroke deaths related to hypertension in women ranged from 12.4% in United Arab Emirates to 48.6% in Bahrain for hemorrhagic stroke and from 10.3% in UAE to 46% in Morocco for ischemic stroke. Overall, up to 60% of stroke can be attributed to the high blood pressure in the Middle East. Stroke is a preventative disease, with this information and better prevention strategies, this region can aim to lower the prevalence of stroke.

The Epidemiology of Stroke Amongst Women in the Asia–Pacific Region

National data from the Asia-Pacific region suggest that stroke accounts for over 10% of female deaths. With general aging in the region, and longer life expectancies for women than men, action is required to maintain recent improvements in female death rates from stroke. However, local data on incidence and risk factors for stroke amongst women are scarce. Data from 214,032 women in the Asia Pacific Cohort Studies Collaboration were thus used to investigate the risk factors for stroke in the region. Raised systolic blood pressure and diabetes were found to be key risk factors for both ischemic (IS) and hemorrhagic (HS) stroke. After adjustment for other risk factors, every extra 10 mmHg systolic blood pressure increased risk of IS by 36% and HS by 69%, whilst diabetes increased risk of IS by 170% and HS by 147%. Smoking was also an important risk factor for IS and HS; risk was reduced by quitting.

Adult height and cancer mortality in Asia: the Asia Pacific Cohort Studies Collaboration

BackgroundThe observation that taller people experience an increased risk of selected cancers is largely restricted to Caucasian cohorts. These associations may plausibly differ in Asian populations. For the first time, we make direct comparison in the same analyses of the associations between height and a series of malignancies in Australasian (Caucasian) and Asian populations. MethodsAnalyses were based on the Asia Pacific Cohort Studies Collaboration of 506648 study participants (408381 Asia, 98267 Australasia) drawn from 38 population-based cohort studies. Cox proportional hazards regression was used to estimate the relationship between height and cancer rates. ResultsA total of 3272600 person-years of follow-up gave rise to 7497 cancer deaths (4415 in Asia; 3082 in Australasia). After multiple adjustments and left censoring, taller individuals experienced increased rates of carcinoma of the intestine (men and women); all cancers, liver, lung, breast, ‘other’ malignancies (all women); and cancers of the prostate and bladder (men). No consistent regional (Asia versus Australasia) or sex differences were observed. ConclusionsIn the present study, taller men and women had an elevated risk of selected malignancies. These associations did not differ appreciably between Asian and Caucasian populations.

Obesity and liver cancer mortality in Asia: The Asia Pacific Cohort Studies Collaboration

While obesity is associated with liver cancer in studies from western societies, the paucity of data from Asia limits insights into its aetiological role in this population. We examined the relationship between body mass index (BMI) and liver cancer mortality using data from the Asia Pacific Cohort Studies Collaboration. In 309,203 Asian study members, 4 years of follow-up gave rise to 11,135 deaths from all causes, 420 of which were ascribed to liver cancer. BMI, whether categorised according to current guidelines for Asian groups or World Health Organisation recommendations, was not associated with liver cancer in any of our analyses.

Smoking and the Risk of Upper Aero Digestive Tract Cancers for Men and Women in the Asia-Pacific Region

Although smoking is an established causal factor for upper aero digestive tract cancer (UADTC), most of the evidence originates from the West. Thus, we analysed data from 455,409 subjects in the Asia Pacific Cohort Studies Collaboration. Over a median of around six years follow-up, 371 deaths from UADTC were observed. The hazard ratio (95% confidence interval) for current smokers, compared with those who had never smoked, was 2.36 (1.76 – 3.16), adjusted for age and alcohol drinking. Tobacco control policies are urgently required in Asia to prevent millions of deaths from UADTC that smoking will otherwise cause.

An update on cardiovascular disease epidemiology in South East Asia. Rationale and design of the LIFE course study in CARdiovascular disease Epidemiology (LIFECARE)

Summary The burden of cardiovascular disease (CVD) is likely to increase dramatically in Asia over the next several decades. In this paper, we review the existing data on CVD epidemiology in Asia, with a focus on the INTERHEART study and the Asia Pacific Cohort Studies Collaboration. Existing data suggests that much of CVD may be preventable through reduction in the levels of well-established CVD risk factors and that these findings are likely to be relevant to Asian populations. However, these studies have several important limitations. These include a lack of longitudinal studies with collection of repeated measures of CVD risk factors and the environmental factors that may result in the age-related increase in the levels of these risk factors. As such, the natural history of the development of CVD risk factors such as obesity, diabetes, hypertension and dyslipidemia in Asia, and their relationship in terms of duration and timing of exposure to various environmental influences is currently unknown. In addition, there is a paucity of data related to psychosocial factors that may be involved in the pathogenesis of CVD, either directly or through effects on other CVD risk factors. Finally, little data is available with regards to the impact of CVD and its attendant risk factors on health related quality of life and health care utilization. This information is crucial for the design and evaluation of evidence based programs for primary prevention. We have designed a LIFE Course Study in CARdiovascular disease Epidemiology (LIFECARE) involving 12,000 individuals in four South East Asian countries to address these data needs.

Adult height and the risks of cardiovascular disease and major causes of death in the Asia-Pacific region: 21 000 deaths in 510 000 men and women

In Caucasian populations, adult height is inversely associated with cardiovascular disease (CVD) risk and positively related to some cancers. However, there are few data from Asian populations and from women. We sought to determine the sex- and region-specific associations between height and cardiovascular outcomes, and deaths due to cancer, respiratory and injury in populations from the Asia-Pacific region. Thirty-nine studies from the Asia Pacific Cohort Studies Collaboration database were included. We used Cox proportional hazard regression models to estimate the associations between height and pre-specified outcomes. A total of 510,800 participants with 21,623 deaths were included. Amongst men, inverse linear associations were observed between height and coronary heart disease (CHD), stroke, CVD, injury and total mortality. The hazard ratios [95% confidence intervals, (CI)] for a 1-SD (= 6 cm) increment in height ranged from 0.85 (0.80-0.91) for injury to 0.97 (0.95-0.98) for total mortality. Similar trends were found between height and CHD, haemorrhagic stroke and CVD in women. A positive linear association was observed between height and cancer mortality. For each standard deviation greater height, the risk of cancer was increased by 5% (2-8%) and 9% (5-14%) in men and women, respectively. No regional difference was observed between Asian and Australasian cohorts. Adjusting for markers of education did not alter the results. The opposing relationships of height with CVD and cancer suggest that care is required in setting national policies on childhood nutrition lest they have unintended consequences on the incidence of major non-communicable diseases.

Elevated total cholesterol: its prevalence and population attributable fraction for mortality from coronary heart disease and ischaemic stroke in the Asia-Pacific region

About half of the world's cases of cardiovascular disease occur in the Asia-Pacific region. The contribution of serum total cholesterol (TC) to this burden is poorly quantified. The most recent nationally representative data on TC distributions for countries in the region were sought. Individual participant data from 380,483 adults in the Asia Pacific Cohort Studies Collaboration were used to estimate associations between TC and cardiovascular disease. High TC was defined as > or =6.2 mmol/l, and nonoptimal TC as > or =3.8 mmol/l. Hazard ratios for fatal coronary heart disease (CHD) and ischaemic stroke (IS) were found from Cox models. Sex-specific population attributable fractions for high TC and nonoptimal TC were estimated for each country. The former used conventional methods, based on single measures of TC and a fixed dichotomy of risk strata; the latter took account of the continuous positive association between TC and both CHD and IS and regression dilution. Data were available from 16 countries. Where reported, the prevalence of high TC ranged from 4 to 27%. The fraction of fatal CHD and IS attributable to high TC ranged from 0 to 14% and 0 to 15%, respectively. Although leaving the relative ranking of countries much the same, the fractions estimated for nonoptimal TC were typically at least twice as big, ranging from 0 to 47% and 0 to 35%, respectively. Conventional methods for estimating disease burden severely underestimate the effect of TC. Cholesterol-lowering strategies could have a tremendous effect in reducing cardiovascular deaths in this populous region.