Displaying publications 1 - 20 of 57 in total

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  1. Anjana RM, Mohan V, Rangarajan S, Gerstein HC, Venkatesan U, Sheridan P, et al.
    Diabetes Care, 2020 12;43(12):3094-3101.
    PMID: 33060076 DOI: 10.2337/dc20-0886
    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.

  2. Arku RE, Brauer M, Ahmed SH, AlHabib KF, Avezum Á, Bo J, et al.
    Environ Pollut, 2020 Jul;262:114197.
    PMID: 32146361 DOI: 10.1016/j.envpol.2020.114197
    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 
  3. Bhavadharini B, Mohan V, Dehghan M, Rangarajan S, Swaminathan S, Rosengren A, et al.
    Diabetes Care, 2020 11;43(11):2643-2650.
    PMID: 32873587 DOI: 10.2337/dc19-2335
    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.

  4. Bhavadharini B, Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, et al.
    PMID: 32423962 DOI: 10.1136/bmjdrc-2019-000826
    OBJECTIVE: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes).

    RESULTS: In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome.

    CONCLUSIONS: Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.

  5. Boakye K, Bovbjerg M, Schuna J, Branscum A, Varma RP, Ismail R, et al.
    Sci Rep, 2023 Jan 06;13(1):290.
    PMID: 36609613 DOI: 10.1038/s41598-022-26406-5
    Urbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003-2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (- 12.4% per IQR, 95% CI - 16.0, - 8.7) and impervious surface area (- 29.2% per IQR, 95% CI - 37.5, - 19.7), as well as the rate of change in 5-year population density (- 17.2% per IQR, 95% CI - 25.7, - 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.
  6. Chow CK, Corsi DJ, Gilmore AB, Kruger A, Igumbor E, Chifamba J, et al.
    BMJ Open, 2017 03 31;7(3):e013817.
    PMID: 28363924 DOI: 10.1136/bmjopen-2016-013817
    OBJECTIVES: This study examines in a cross-sectional study 'the tobacco control environment' including tobacco policy implementation and its association with quit ratio.

    SETTING: 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community's Health (EPOCH) study from 2009 to 2014.

    PARTICIPANTS: Community audits and surveys of adults (35-70 years, n=12 953).

    PRIMARY AND SECONDARY OUTCOME MEASURES: Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models.

    RESULTS: Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example, communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5·0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1).

    CONCLUSIONS: This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.

  7. Chow CK, Ramasundarahettige C, Hu W, AlHabib KF, Avezum A, Cheng X, et al.
    Lancet Diabetes Endocrinol, 2018 10;6(10):798-808.
    PMID: 30170949 DOI: 10.1016/S2213-8587(18)30233-X
    BACKGROUND: Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use.

    METHODS: In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys.

    FINDINGS: Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines.

    INTERPRETATION: Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

  8. Dagenais GR, Gerstein HC, Zhang X, McQueen M, Lear S, Lopez-Jaramillo P, et al.
    Diabetes Care, 2016 05;39(5):780-7.
    PMID: 26965719 DOI: 10.2337/dc15-2338
    OBJECTIVE: The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors.

    RESEARCH DESIGN AND METHODS: The prevalence of diabetes, defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses.

    RESULTS: Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28-1.31]), male sex (1.19 [1.13-1.25]), urban residency (1.24 [1.11-1.38]), low versus high education level (1.10 [1.02-1.19]), low versus high physical activity (1.28 [1.20-1.38]), family history of diabetes (3.15 [3.00-3.31]), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33-3.96]), and BMI (≥35 vs. <25 kg/m(2); 2.76 [2.52-3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%).

    CONCLUSIONS: Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.

  9. Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, Iqbal R, et al.
    Lancet, 2018 11 24;392(10161):2288-2297.
    PMID: 30217460 DOI: 10.1016/S0140-6736(18)31812-9
    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).

  10. Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V, et al.
    Lancet, 2017 Nov 04;390(10107):2050-2062.
    PMID: 28864332 DOI: 10.1016/S0140-6736(17)32252-3
    BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

    FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

    INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

  11. Dehghan M, Mente A, Rangarajan S, Mohan V, Swaminathan S, Avezum A, et al.
    Am J Clin Nutr, 2023 Jan;117(1):55-63.
    PMID: 36789944 DOI: 10.1016/j.ajcnut.2022.10.014
    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.

  12. Dehghan M, Mente A, Rangarajan S, Mohan V, Lear S, Swaminathan S, et al.
    Am J Clin Nutr, 2020 04 01;111(4):795-803.
    PMID: 31965140 DOI: 10.1093/ajcn/nqz348
    BACKGROUND: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries.

    OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries.

    METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study.

    RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12).

    CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. The ONTARGET and TRANSCEND trials were registered at clinicaltrials.gov as NCT00153101. The PURE trial was registered at clinicaltrials.gov as NCT03225586.

  13. Duong M, Islam S, Rangarajan S, Leong D, Kurmi O, Teo K, et al.
    Lancet Glob Health, 2019 05;7(5):e613-e623.
    PMID: 31000131 DOI: 10.1016/S2214-109X(19)30070-1
    BACKGROUND: The associations between the extent of forced expiratory volume in 1 s (FEV1) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown.

    METHODS: In this international, community-based cohort study, we prospectively enrolled adults aged 35-70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV1. FEV1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV1 value (FEV1%). FEV1% was categorised as no impairment (FEV1% ≥0 SD from country-specific mean), mild impairment (FEV1% <0 SD to -1 SD), moderate impairment (FEV1%

  14. Hussain R, Ullah H, Rahim F, Sarfraz M, Taha M, Iqbal R, et al.
    Molecules, 2022 Sep 18;27(18).
    PMID: 36144820 DOI: 10.3390/molecules27186087
    Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.
  15. Hystad P, Larkin A, Rangarajan S, AlHabib KF, Avezum Á, Calik KBT, et al.
    Lancet Planet Health, 2020 06;4(6):e235-e245.
    PMID: 32559440 DOI: 10.1016/S2542-5196(20)30103-0
    BACKGROUND: Most studies of long-term exposure to outdoor fine particulate matter (PM2·5) and cardiovascular disease are from high-income countries with relatively low PM2·5 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM2·5 contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to PM2·5 concentrations and cardiovascular disease in a large cohort of adults from 21 high-income, middle-income, and low-income countries.

    METHODS: In this multinational, prospective cohort study, we studied 157 436 adults aged 35-70 years who were enrolled in the PURE study in countries with ambient PM2·5 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM2·5 concentrations and cardiovascular disease events (fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality.

    FINDINGS: Between Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9·3 years (IQR 7·8-10·8; corresponding to 1·4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5·8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM2·5 at cohort baseline was 47·5 μg/m3 (range 6-140). In models adjusted for individual, household, and geographical factors, a 10 μg/m3 increase in PM2·5 was associated with increased risk for cardiovascular disease events (hazard ratio 1·05 [95% CI 1·03-1·07]), myocardial infarction (1·03 [1·00-1·05]), stroke (1·07 [1·04-1·10]), and cardiovascular disease mortality (1·03 [1·00-1·05]). Results were similar for LMICs and communities with high PM2·5 concentrations (>35 μg/m3). The population attributable fraction for PM2·5 in the PURE cohort was 13·9% (95% CI 8·8-18·6) for cardiovascular disease events, 8·4% (0·0-15·4) for myocardial infarction, 19·6% (13·0-25·8) for stroke, and 8·3% (0·0-15·2) for cardiovascular disease mortality. We identified no consistent associations between PM2·5 and risk for non-cardiovascular disease deaths.

    INTERPRETATION: Long-term outdoor PM2·5 concentrations were associated with increased risks of cardiovascular disease in adults aged 35-70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest.

    FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

  16. Iqbal R, Dehghan M, Mente A, Rangarajan S, Wielgosz A, Avezum A, et al.
    Am J Clin Nutr, 2021 09 01;114(3):1049-1058.
    PMID: 33787869 DOI: 10.1093/ajcn/nqaa448
    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.

  17. Jenkins DJA, Dehghan M, Mente A, Bangdiwala SI, Rangarajan S, Srichaikul K, et al.
    N Engl J Med, 2021 04 08;384(14):1312-1322.
    PMID: 33626252 DOI: 10.1056/NEJMoa2007123
    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.).

  18. Joseph P, Yusuf S, Lee SF, Ibrahim Q, Teo K, Rangarajan S, et al.
    Heart, 2018 04;104(7):581-587.
    PMID: 29066611 DOI: 10.1136/heartjnl-2017-311609
    OBJECTIVE: To evaluate the performance of the non-laboratory INTERHEART risk score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven major geographic regions of the world. The secondary objective was to evaluate the performance of the fasting cholesterol-based IHRS (FC-IHRS).

    METHODS: Using measures of discrimination and calibration, we tested the performance of the NL-IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a community-based, prospective study across seven geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/North America, South America and Africa. CVD was defined as the composite of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularisation.

    RESULTS: Mean age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89 (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD across geographic regions (concordance statistic (C-statistic) ranging from 0.64 to 0.74), although recalibration was necessary in all regions, which improved its performance in the overall cohort (increase in C-statistic from 0.69 to 0.72, p<0.001). Regional recalibration was also necessary for the FC-IHRS, which also improved its overall discrimination (increase in C-statistic from 0.71 to 0.74, p<0.001). In 85 078 participants with complete data for both scores, discrimination was only modestly better with the FC-IHRS compared with the NL-IHRS (0.74 vs 0.73, p<0.001).

    CONCLUSIONS: External validations of the NL-IHRS and FC-IHRS suggest that regionally recalibrated versions of both can be useful for estimating CVD risk across a diverse range of community-based populations. CVD prediction using a non-laboratory score can provide similar accuracy to laboratory-based methods.

  19. Khetan AK, Leong DP, Gupta R, Zhu Y, Li S, Liu W, et al.
    Int J Epidemiol, 2021 Dec 22.
    PMID: 34939099 DOI: 10.1093/ije/dyab268
    BACKGROUND: Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world.

    METHODS: The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3-12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer.

    RESULTS: A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90-0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94-1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18-1.28). The interaction p-values between height and country-income level for all three outcomes were <0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84-0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82-0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99-1.32), 1.12 (95% CI 1.04-1.22) and 1.20 (95% CI 1.14-1.26).

    CONCLUSIONS: Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level.

  20. Langhorne P, O'Donnell MJ, Chin SL, Zhang H, Xavier D, Avezum A, et al.
    Lancet, 2018 05 19;391(10134):2019-2027.
    PMID: 29864018 DOI: 10.1016/S0140-6736(18)30802-X
    BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels.

    METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month.

    FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics.

    INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes.

    FUNDING: Chest, Heart and Stroke Scotland.

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