Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality.

BACKGROUND: Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population. METHODS: This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause. RESULTS: In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease. CONCLUSIONS: In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.).

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries.

AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113). INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study.

BACKGROUND: WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality. METHODS: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders. FINDINGS: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries. INTERPRETATION: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate. FUNDING: Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study.

BACKGROUND: The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia. METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality. FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality. INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day). FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data.

BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, ß blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55). INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Association of urinary sodium and potassium excretion with blood pressure.

BACKGROUND: Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown. METHODS: We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device. RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).

Cardiovascular risk and events in 17 low-, middle-, and high-income countries.

BACKGROUND: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).

Wealth and cardiovascular health: a cross-sectional study of wealth-related inequalities in the awareness, treatment and control of hypertension in high-, middle- and low-income countries.

BACKGROUND: Effective policies to control hypertension require an understanding of its distribution in the population and the barriers people face along the pathway from detection through to treatment and control. One key factor is household wealth, which may enable or limit a household's ability to access health care services and adequately control such a chronic condition. This study aims to describe the scale and patterns of wealth-related inequalities in the awareness, treatment and control of hypertension in 21 countries using baseline data from the Prospective Urban and Rural Epidemiology study. METHODS: A cross-section of 163,397 adults aged 35 to 70 years were recruited from 661 urban and rural communities in selected low-, middle- and high-income countries (complete data for this analysis from 151,619 participants). Using blood pressure measurements, self-reported health and household data, concentration indices adjusted for age, sex and urban-rural location, we estimate the magnitude of wealth-related inequalities in the levels of hypertension awareness, treatment, and control in each of the 21 country samples. RESULTS: Overall, the magnitude of wealth-related inequalities in hypertension awareness, treatment, and control was observed to be higher in poorer than in richer countries. In poorer countries, levels of hypertension awareness and treatment tended to be higher among wealthier households; while a similar pro-rich distribution was observed for hypertension control in countries at all levels of economic development. In some countries, hypertension awareness was greater among the poor (Sweden, Argentina, Poland), as was treatment (Sweden, Poland) and control (Sweden). CONCLUSION: Inequality in hypertension management outcomes decreased as countries became richer, but the considerable variation in patterns of wealth-related inequality - even among countries at similar levels of economic development - underscores the importance of health systems in improving hypertension management for all. These findings show that some, but not all, countries, including those with limited resources, have been able to achieve more equitable management of hypertension; and strategies must be tailored to national contexts to achieve optimal impact at population level.

The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries.

OBJECTIVE: To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing. METHODS: Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders. FINDINGS: Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities. CONCLUSION: Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study.

BACKGROUND: Higher intake of ultra-processed foods (UPFs) has been associated with increased risk of CVD and mortality in observational studies from Western countries but data from non-Western countries are limited. OBJECTIVES: We aimed to assess the association between consumption of UPFs and risk of mortality and major CVD in a cohort from multiple world regions. DESIGN: This analysis includes 138,076 participants without a history of CVD between the ages of 35 and 70 y living on 5 continents, with a median follow-up of 10.2 y. We used country-specific validated food-frequency questionnaires to determine individuals' food intake. We classified foods and beverages based on the NOVA classification into UPFs. The primary outcome was total mortality (CV and non-CV mortality) and secondary outcomes were incident major cardiovascular events. We calculated hazard ratios using multivariable Cox frailty models and evaluated the association of UPFs with total mortality, CV mortality, non-CV mortality, and major CVD events. RESULTS: In this study, 9227 deaths and 7934 major cardiovascular events were recorded during the follow-up period. We found a diet high in UPFs (≥2 servings/d compared with 0 intake) was associated with higher risk of mortality (HR: 1.28; 95% CI: 1.15, 1.42; P-trend < 0.001), CV mortality (HR: 1.17; 95% CI: 0.98, 1.41; P-trend = 0.04), and non-CV mortality (HR: 1.32; 95% CI 1.17, 1.50; P-trend < 0.001). We did not find a significant association between UPF intake and risk of major CVD. CONCLUSIONS: A diet with a high intake of UPFs was associated with a higher risk of mortality in a diverse multinational study. Globally, limiting the consumption of UPFs should be encouraged.

Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries.

Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied. Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents. Design, Setting, and Participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021. Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress. Main Outcomes and Measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality. Results: A total of 118 706 participants (mean [SD] age 50.4 [9.6] years; 69 842 [58.8%] women and 48 864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21 797 participants (18.4%) reported moderate stress, 34 958 participants (29.4%) reported low stress, and 53 252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10 599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10 477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13 222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20 255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment. Conclusions and Relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events.

Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study.

OBJECTIVE: To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study. DESIGN: Prospective cohort study. SETTING: PURE study in 21 countries. PARTICIPANTS: 148 858 participants with median follow-up of 9.5 years. EXPOSURES: Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice. MAIN OUTCOME MEASURE: Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre. RESULTS: Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes. CONCLUSION: High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.

Timing and Length of Nocturnal Sleep and Daytime Napping and Associations With Obesity Types in High-, Middle-, and Low-Income Countries.

Importance: Obesity is a growing public health threat leading to serious health consequences. Late bedtime and sleep loss are common in modern society, but their associations with specific obesity types are not well characterized. Objective: To assess whether sleep timing and napping behavior are associated with increased obesity, independent of nocturnal sleep length. Design, Setting, and Participants: This large, multinational, population-based cross-sectional study used data of participants from 60 study centers in 26 countries with varying income levels as part of the Prospective Urban Rural Epidemiology study. Participants were aged 35 to 70 years and were mainly recruited during 2005 and 2009. Data analysis occurred from October 2020 through March 2021. Exposures: Sleep timing (ie, bedtime and wake-up time), nocturnal sleep duration, daytime napping. Main Outcomes and Measures: The primary outcomes were prevalence of obesity, specified as general obesity, defined as body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or greater, and abdominal obesity, defined as waist circumference greater than 102 cm for men or greater than 88 cm for women. Multilevel logistic regression models with random effects for study centers were performed to calculate adjusted odds ratios (AORs) and 95% CIs. Results: Overall, 136 652 participants (81 652 [59.8%] women; mean [SD] age, 51.0 [9.8] years) were included in analysis. A total of 27 195 participants (19.9%) had general obesity, and 37 024 participants (27.1%) had abdominal obesity. The mean (SD) nocturnal sleep duration was 7.8 (1.4) hours, and the median (interquartile range) midsleep time was 2:15 am (1:30 am-3:00 am). A total of 19 660 participants (14.4%) had late bedtime behavior (ie, midnight or later). Compared with bedtime between 8 pm and 10 pm, late bedtime was associated with general obesity (AOR, 1.20; 95% CI, 1.12-1.29) and abdominal obesity (AOR, 1.20; 95% CI, 1.12-1.28), particularly among participants who went to bed between 2 am and 6 am (general obesity: AOR, 1.35; 95% CI, 1.18-1.54; abdominal obesity: AOR, 1.38; 95% CI, 1.21-1.58). Short nocturnal sleep of less than 6 hours was associated with general obesity (eg, <5 hours: AOR, 1.27; 95% CI, 1.13-1.43), but longer napping was associated with higher abdominal obesity prevalence (eg, ≥1 hours: AOR, 1.39; 95% CI, 1.31-1.47). Neither going to bed during the day (ie, before 8pm) nor wake-up time was associated with obesity. Conclusions and Relevance: This cross-sectional study found that late nocturnal bedtime and short nocturnal sleep were associated with increased risk of obesity prevalence, while longer daytime napping did not reduce the risk but was associated with higher risk of abdominal obesity. Strategic weight control programs should also encourage earlier bedtime and avoid short nocturnal sleep to mitigate obesity epidemic.

Associations of unprocessed and processed meat intake with mortality and cardiovascular disease in 21 countries [Prospective Urban Rural Epidemiology (PURE) Study]: a prospective cohort study.

BACKGROUND: Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent. OBJECTIVE: The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD. METHODS: The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts. RESULTS: In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs. <50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004). CONCLUSIONS: In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

Contrasting Associations Between Diabetes and Cardiovascular Mortality Rates in Low-, Middle-, and High-Income Countries: Cohort Study Data From 143,567 Individuals in 21 Countries in the PURE Study.

OBJECTIVE: We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income. RESEARCH DESIGN AND METHODS: The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years. RESULTS: Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]). CONCLUSIONS: CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.

White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries.

OBJECTIVE: Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS: Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, ≥150 to <300, ≥300 to <450, and ≥450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS: During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (≥450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40; P for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; P for trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86; P for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; P for trend = 0.38). CONCLUSIONS: Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.

Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study.

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 µg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 µg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 µg/m3) compared to the first (PM2.5 < 14 µg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (ß = 2.15 mmHg, 95% CI: -0.59, 4.89) and diastolic BP (ß = 1.35, 95% CI: -0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (-0.51 mmHg; 95% CI: -0.99, -0.03) and diastolic (-0.46 mmHg; 95% CI: -0.75, -0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.