Publications by authors named "Sumathy Rangarajan"

114 Publications

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

N Engl J Med 2021 Feb 24. Epub 2021 Feb 24.

From the Departments of Nutritional Sciences and Medicine, Temerty Faculty of Medicine, University of Toronto (D.J.A.J.), and Li Ka Shing Knowledge Institute, St. Michael's Hospital Toronto (D.J.A.J., K.S.), Toronto, the Population Health Research Institute (M.D., S.I.B., K.T., S.Y.) and Department of Health Research Methods, Evidence, and Impact (A.M., S.I.B.), McMaster University, and McMaster University and Hamilton Health Sciences (S.R.), Hamilton, ON, Faculté de Pharmacie, Université Laval, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC (P.P.), the Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa (A.P.), and the Department of Medicine, Queen's University, Kingston, ON (K. Yeates) - all in Canada; the Madras Diabetes Research Foundation, Chennai (V.M.), and St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore (S.S.) - both in India; the International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo (A.A.); Estudios Clínicos Latino América, Rosario, Santa Fe, Argentina (R.D.); the Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, and Sahlgrenska University Hospital, Gothenburg, Sweden (A.R.); Universidad de la Frontera, Temuco, Chile (F.L.); the Masira Research Institute, Medical School, Universidad de Santander, Bucaramanga, Colombia (P.L.-J.); the Medical Research and Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing (W.L., X.L.); the Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey (A.O.); the Institute for Community and Public Health, Birzeit University, Birzeit, Palestine (R.K.); Advocate Research Institute, Advocate Health Care, Downers Grove, IL (R.K.); Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran (N.M.); the Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia (K.F.A.); the Department of Physiology, University of Zimbabwe College of Health Sciences, Harare (J.C.); Hatta Hospital, Dubai Medical College, Dubai Health Authority, Dubai, United Arab Emirates (A.H.Y.); the Department of Community Health Sciences and Medicine, Aga Khan University, Pakistan (R.I.); Universiti Teknologi MARA, Sungai Buloh, and UCSI University, Selangor (K. Yusoff), and the Department of Community Health, University Kebangsaan Malaysia Medical Center, Kuala Lumpur (N.I.) - both in Malaysia; the Department of Social Medicine, Wroclaw Medical University, Wroclaw, Poland (K.Z.); and the School of Life Sciences, Independent University, Dhaka, Bangladesh (R.Y.).

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.).
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http://dx.doi.org/10.1056/NEJMoa2007123DOI Listing
February 2021

Association of bedtime with mortality and major cardiovascular events: an analysis of 112,198 individuals from 21 countries in the PURE study.

Sleep Med 2021 Feb 5;80:265-272. Epub 2021 Feb 5.

Population Health Research Institute, McMaster University, Hamilton, ON, Canada. Electronic address:

Objectives: This study aimed to examine the association of bedtime with mortality and major cardiovascular events.

Methods: Bedtime was recorded based on self-reported habitual time of going to bed in 112,198 participants from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Participants were prospectively followed for 9.2 years. We examined the association between bedtime and the composite outcome of all-cause mortality, non-fatal myocardial infarction, stroke and heart failure. Participants with a usual bedtime earlier than 10PM were categorized as 'earlier' sleepers and those who reported a bedtime after midnight as 'later' sleepers. Cox frailty models were applied with random intercepts to account for the clustering within centers.

Results: A total of 5633 deaths and 5346 major cardiovascular events were reported. A U-shaped association was observed between bedtime and the composite outcome. Using those going to bed between 10PM and midnight as the reference group, after adjustment for age and sex, both earlier and later sleepers had a higher risk of the composite outcome (HR of 1.29 [1.22, 1.35] and 1.11 [1.03, 1.20], respectively). In the fully adjusted model where demographic factors, lifestyle behaviors (including total sleep duration) and history of diseases were included, results were greatly attenuated, but the estimates indicated modestly higher risks in both earlier (HR of 1.09 [1.03-1.16]) and later sleepers (HR of 1.10 [1.02-1.20]).

Conclusion: Early (10 PM or earlier) or late (Midnight or later) bedtimes may be an indicator or risk factor of adverse health outcomes.
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http://dx.doi.org/10.1016/j.sleep.2021.01.057DOI Listing
February 2021

Fruit, vegetable, and legume intake and the risk of all-cause, cardiovascular, and cancer mortality: A prospective study.

Clin Nutr 2021 Jan 27. Epub 2021 Jan 27.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

Background & Aims: Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality.

Methods: In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality.

Results: A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 [standard deviation (SD) 1.22] servings per day. During a median follow-up of 8.9 years [interquartile range (IQR) 6.7-9.9 years], we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio [HR] trend 0.92, 95% CI 0.86-0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97-1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84-1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89-1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82-1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55-0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86-0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90-0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89-0.99, p trend = 0.020) in the fully adjusted models.

Conclusions: This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500-625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.
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http://dx.doi.org/10.1016/j.clnu.2021.01.016DOI Listing
January 2021

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

BMJ 2021 02 3;372:m4948. Epub 2021 Feb 3.

Population Health Research Institute (PHRI), McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada.

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.
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http://dx.doi.org/10.1136/bmj.m4948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856570PMC
February 2021

Tyrosine kinase inhibitors in chronic myeloid leukaemia and emergent cardiovascular disease.

Heart 2021 Jan 8. Epub 2021 Jan 8.

Oncology, McMaster University, Hamilton, Ontario, Canada.

Objectives: (1) Describe how the risk of major adverse cardiovascular events (MACE) in individuals with chronic myeloid leukaemia (CML) has evolved; (2) evaluate the risk of MACE associated with the prescription of different CML tyrosine kinase inhibitors (TKI).

Methods: A population-based retrospective study including all patients (n=4238) diagnosed with CML in Ontario, Canada between 1986 and 2017 and and age-matched and sex-matched individuals who received healthcare but who did not have CML (controls: n=42 380). The cohort was divided into those entering before 2001 vs from 2001 onwards (when TKIs were introduced). We developed competing risks models to compare time-to-event in CML cases versus controls. We adjusted for baseline comorbidities and present subdistribution HRs and 95% CIs. The relationship between TKI use and MACE was assessed by logistic regression.

Results: Before 2001 and from 2001 on, patients with CML had a higher crude incidence of MACE than patients without CML (19.8 vs 15.3 and 20.3 vs 12.6 per 1000 person-years, respectively). After adjustment for cardiovascular risk factors, patients with CML had a lower subdistribution hazard for MACE (0.59, 95% CI 0.46 to 0.76) before 2001; but from 2001, the adjusted subdistribution HR for MACE (1.27, 95% CI 0.96 to 1.43) was similar to age-matched and sex-matched patients. The incidence (9.3 vs 13.8 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.43, 95% CI 0.36 to 0.52) were lower in patients with CML than controls before 2001. From 2001 on, the incidence (6.3 vs 5.4 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.99, 95% CI 0.84 to 1.18) were similar to age-matched and sex-matched patients without CML with a higher risk of cerebrovascular events (8.6 vs 5.6 per 1000 person-years; 1.35, 95% CI 1.00 to 1.83) and peripheral arterial events (6.9 vs 3.0 per 1000 person-years; 1.66 95% CI, 1.15 to 2.39) in patients with CML than patients without CML. Compared with imatinib, there was no difference in the risk of MACE among those prescribed dasatinib (OR 0.67, 95% CI 0.41 to 1.10) or nilotinib (OR 1.22, 95% CI 0.70 to 1.97).

Conclusions: In a contemporary CML population, the risk of MACE and cardiovascular death is at least as high as among age-matched and sex-matched patients without CML and may be higher for cerebrovascular and peripheral arterial events. No difference in the risk of MACE between imatinib, dasatinib and nilotinib was observed.
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http://dx.doi.org/10.1136/heartjnl-2020-318251DOI Listing
January 2021

Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level.

Heart 2020 Dec 14. Epub 2020 Dec 14.

Dept of Medicine, Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

Objective: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke.

Methods: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension.

Results: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46).

Conclusions: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.
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http://dx.doi.org/10.1136/heartjnl-2019-316515DOI Listing
December 2020

Low levels of awareness, treatment, and control of hypertension in Andean communities of Ecuador.

J Clin Hypertens (Greenwich) 2020 Sep 15;22(9):1530-1537. Epub 2020 Aug 15.

Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador.

The major burden of hypertension (HTN) occurs in low-middle-income countries (LMIC) and it is the main modifiable risk factor for cardiovascular diseases (CVD). Few population studies on HTN prevalence have been carried out in Ecuador where there is limited information regarding its prevalence, awareness, treatment, and control. Thus, the aim of the present study was to determine the prevalence, awareness, treatment, and control of HTN and its association with socio-economic, nutritional, and lifestyle habits in urban and rural Andean communities of Pichincha province in Ecuador. The authors studied 2020 individuals aged 35-70 years (mean age 50.8 years, 72% women), included in the Ecuadorian cohort of the Prospective Urban and Rural Epidemiology (PURE) study, from February to December 2018. The hypertension prevalence (>140/90 mmHg) was 27% and was greater in urban than in rural communities, more common in men, in individuals older than 50 years of age, in people with low monthly income and low level of education. Higher prevalence was also observed in subjects with obesity, and among former smokers and those who consumed alcohol. Only 49% of those with HTN were aware of their condition, 40% were using antihypertensive medications, and 19% had their blood pressure under control (<140/90 mmHg). These results showed low levels of awareness, treatment, and control of HTN in the Andean region of Ecuador, suggesting the urgent necessity of implementing programs to improve the diagnosis and management of HTN.
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http://dx.doi.org/10.1111/jch.13982DOI Listing
September 2020

Urinary Sodium and Potassium, and Risk of Ischaemic and Haemorrhagic Stroke (INTERSTROKE): a case-control study.

Am J Hypertens 2020 Nov 17. Epub 2020 Nov 17.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Background: Although low sodium intake (<2g/day) and high potassium intake (>3·5g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke and its subtypes.

Methods: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls (8,761 matched pairs for conditional analysis) from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.

Results: The mean estimated 24-hour sodium and potassium urinary excretion was 3·29g/day and 1·57g/day, with 0·01% of participants having both low sodium (<2·0g/day) and high potassium excretion (>3·5g/day). There was a moderate positive correlation between sodium and potassium excretion (r=0·4435, P<0.001) and between sodium excretion and blood pressure (P<0.001). Compared with an estimated urinary sodium excretion of 2·8-3·5g/day (second quartile, reference), higher (>4·26g/day) (OR 1.81;95%CI,1.65-2.00) and lower (<2·8g/day) sodium excretion (OR 1.39;95%CI,1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4·26g/day) was significantly greater (P<0.001) for intracerebral haemorrhage (ICH) (OR 2.38;95%CI,1.93-2.92) than for ischemic stroke (OR 1.67;95%CI,1.50-1.87), and greater for large vessel and small vessel ischemic stroke than for cardioembolic ischemic stroke. Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P=0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1·58g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke.

Conclusion: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for intracerebral haemorrhage than ischemic stroke. Our data suggest that moderate sodium intake - rather than low sodium intake - combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
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http://dx.doi.org/10.1093/ajh/hpaa176DOI Listing
November 2020

Associations of household solid fuel for heating and cooking with hypertension in Chinese adults.

J Hypertens 2021 Apr;39(4):667-676

JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China.

Objective: The association between indoor air pollution resulting from household solid fuel use for heating and cooking with hypertension or blood pressure (BP) remains less clear. This study aims to rectify these knowledge gaps in a large Chinese population.

Methods: During 2005-2009, 44 007 individuals aged 35-70 years with complete information on household solid fuel use for cooking and heating were recruited from 279 urban and rural communities of 12 centers. Solid fuel referred to charcoal, coal, wood, agriculture crop, animal dung or shrub. Annual concentration of ambient atmospheric particulate matter that have a diameter of less than 2.5 μm for all communities was collected. Generalized linear mixed models using community as the random effect were performed to estimate the association with hypertension prevalence or BP after considering ambient atmospheric particulate matter that have a diameter of less than 2.5 μm and a comprehensive set of potential confounding factors at the individual and household level.

Results: A total of 47.6 and 61.2% of participants used household solid fuel for heating and cooking, respectively. Solid fuel use for heating was not associated with an increase in hypertension prevalence (adjusted odds ratio = 1.08, 95% confident interval: 0.98, 1.20) or elevated SBP (0.62 mmHg, 95% confident interval: -0.24, 1.48). No association was found between solid fuel for cooking and hypertension or BP, and no additional risk was observed among participants who had both exposures to solid fuel for heating and cooking compared with those used for heating only.

Conclusion: The current large Chinese study revealed a statistically insignificant increase in the association between solid fuel use for heating and hypertension prevalence or BP. As this cross-sectional study has its inherent limitation on causality, findings from this study would have to be confirmed by prospective cohort studies.
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http://dx.doi.org/10.1097/HJH.0000000000002689DOI Listing
April 2021

Availability and affordability of medicines and cardiovascular outcomes in 21 high-income, middle-income and low-income countries.

BMJ Glob Health 2020 11;5(11)

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Objectives: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study.

Methods: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors.

Results: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50).

Conclusion: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.
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http://dx.doi.org/10.1136/bmjgh-2020-002640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640501PMC
November 2020

The association of grip strength with cardiovascular diseases and all-cause mortality in people with hypertension: Findings from the Prospective Urban Rural Epidemiology China Study.

J Sport Health Sci 2020 Oct 19. Epub 2020 Oct 19.

Medical Research & Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 102300, China. Electronic address:

Background: Both hypertension and grip strength (GS) are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to affect CVD and all-cause mortality is unknown. This study sought to investigate the associations of GS with the risk of major CVD incidence, CVD mortality, and all-cause mortality in patients with hypertension.

Methods: GS was measured using a Jamar dynamometer (Sammons Preston, Bolingbrook, IL, USA) in participants aged 35-70 years from 12 provinces included in the Prospective Urban Rural Epidemiology China study. Cox frailty proportional hazards models were used to examine the associations of GS and hypertension and the outcomes of all-cause mortality and CVD incidence/mortality.

Results: Among 39,862 participants included in this study, 15,964 reported having hypertension, and 9095 had high GS at baseline. After a median follow-up of 8.9 years (interquartile range, 6.7-9.9 years), 1822 participants developed major CVD, and 1250 deaths occurred (388 as a result of CVD). Compared with normotensive participants with high GS, hypertensive patients with high GS had a higher risk of major CVD incidence (hazard ratio (HR) = 2.39; 95% confidence interval (CI): 1.86-3.06; p < 0.001) or CVD mortality (HR = 3.11; 95%CI: 1.59-6.06; p < 0.001) but did not have a significantly increased risk of all-cause mortality (HR = 1.24; 95%CI: 0.92-1.68; p = 0.159). These risks were further increased if hypertensive participants whose GS level was low (major CVD incidence, HR = 3.31, 95%CI: 2.60-4.22, p < 0.001; CVD mortality, HR = 4.99, 95%CI: 2.64-9.43, p < 0.001; and all-cause mortality, HR = 1.93, 95%CI: 1.47-2.53, p < 0.001).

Conclusion: The present study demonstrates that low GS is associated with the highest risk of major CVD incidence, CVD mortality, and all-cause mortality among hypertensive patients. High levels of GS appear to mitigate long-term mortality risk among hypertensive patients.
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http://dx.doi.org/10.1016/j.jshs.2020.10.005DOI Listing
October 2020

"Cerebral small vessel disease and other influential factors of cognitive impairment in the middle-aged: a long-term observational cohort PURE-MIND study in Poland".

Geroscience 2020 Oct 19. Epub 2020 Oct 19.

Department of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland.

A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess the prevalence and determinants of cognitive impairment, including the role of cerebral small vessel disease (CSVD) in Polish middle-aged cohort. A comprehensive set of clinical (hypertension, coronary heart disease, diabetes mellitus, hyperlipidaemia, body mass index, smoking status, alcohol intake) and socio-demographic data was collected in the PURE study in years 2007-2016, which was the basis for detailed analysis of risk factors of cognitive impairments in years 2016-2018 in the PURE-MIND sub-study. Five hundred forty-seven subjects (age range 39-65, mean 56.2 ± 6.5) underwent neuropsychological assessment with Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT) and Digit Symbol Substitution Test (DSST) followed by brain MRI. Mean MoCA score was 26.29 and 33% participants met criteria for mild cognitive impairment (MCI) (MoCA< 26). Seventy-three percent showed findings related to CSVD. Higher WMH burden and lacunar infarcts were associated with lower MoCA and DSST scores. Severe CSVD was associated with twofold incidence of MCI, and obesity increased its probability by 53% and hypertension by 37%. The likelihood of MCI was reduced in nonsmokers. One factor analysis showed the important role of lower level of education, older age, rural area of residence and hypertension. MCI and CSVD are highly prevalent in the middle-aged population in Poland. A greater importance should be given to potentially modifiable risk factors of dementia which are already present in mid-life.
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http://dx.doi.org/10.1007/s11357-020-00271-4DOI Listing
October 2020

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.

Diabetes Care 2020 Dec 15;43(12):3094-3101. Epub 2020 Oct 15.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

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, < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, < 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.
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http://dx.doi.org/10.2337/dc20-0886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770267PMC
December 2020

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

Lancet Planet Health 2020 10;4(10):e451-e462

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.

Background: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM and black carbon in rural communities with a wide range of cooking environments.

Methods: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM measurements were collected. Light absorbance (10m) of the PM filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period.

Findings: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM kitchen concentration gradient emerged across primary cooking fuels: gas (45 μg/m [95% CI 43-48]), electricity (53 μg/m [47-60]), coal (68 μg/m [61-77]), charcoal (92 μg/m [58-146]), agricultural or crop waste (106 μg/m [91-125]), wood (109 μg/m [102-118]), animal dung (224 μg/m [197-254]), and shrubs or grass (276 μg/m [223-342]). Among households cooking primarily with wood, average PM concentrations varied ten-fold (range: 40-380 μg/m). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM personal exposures between women (67 μg/m [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women).

Interpretation: Using clean primary fuels substantially lowers kitchen PM concentrations. Importantly, average kitchen and personal PM measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 μg/m annual average), highlighting the need for comprehensive pollution mitigation strategies.

Funding: Canadian Institutes for Health Research, National Institutes of Health.
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http://dx.doi.org/10.1016/S2542-5196(20)30197-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591267PMC
October 2020

Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis.

Lancet 2020 10;396(10256):968-976

Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada. Electronic address:

Background: Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events.

Methods: We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events.

Findings: We included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29-1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10-1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13-1·33]), stroke (HR 1·21 per 1 SD increase [1·10-1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36-1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction.

Interpretation: Increased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study.

Funding: Canadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.
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http://dx.doi.org/10.1016/S0140-6736(20)31964-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529405PMC
October 2020

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

Diabetes Care 2020 Nov 1;43(11):2643-2650. Epub 2020 Sep 1.

Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.

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; for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; 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; for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; 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.
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http://dx.doi.org/10.2337/dc19-2335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576435PMC
November 2020

Risk of cardiovascular events in patients with metabolic syndrome: Results of a population-based prospective cohort study (PURE Turkey).

Anatol J Cardiol 2020 09;24(3):192-200

Population Health Research Institute, McMaster University and Hamilton Health Sciences; Hamilton, ON-Canada.

Objective: Metabolic syndrome (MetS) includes several cardiovascular (CV) risk factors. This study aimed to assess CV risk of MetS, contribution of its components to the risk, and whether MetS provides additional risk beyond its components.

Methods: The Prospective Urban Rural Epidemiology (PURE) Turkey cohort included 3933 individuals aged between 35 and 70 years, with a median follow-up of 8.9 years. MetS was diagnosed as the presence of any of the following criteria: high blood pressure, high fasting plasma glucose, abdominal obesity, low HDL-cholesterol, or high triglycerides. The primary outcome was the composite of fatal CV events, non-fatal myocardial infarction, stroke or heart failure, adjusted for age, sex, smoking, family history of CV diseases, and LDL-cholesterol.

Results: The primary outcome was more common in the MetS group [178 (9.2%) vs. 70 (3.5%); corresponding incidence rate of 11.3 vs. 4.2 per 1000 person-years; log-rank p<0.001]. Each component was significantly associated with the primary outcome; however, when the components were sequentially included in the model, abdominal obesity and high triglycerides did not provide additional risk on top of the other three components. The hazard ratio for MetS for the primary outcome was 2.12 (95% confidence interval 1.59-2.81, p<0.001), and the discriminative ability (c-statistics) of the models with MetS and the components was similar.

Conclusion: MetS increases the risk of CV events more than two-fold. High blood pressure, high fasting plasma glucose, and low HDL-cholesterol are the top three components of MetS for CV risk. MetS and its components have a similar discriminative ability for CV events.
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http://dx.doi.org/10.14744/AnatolJCardiol.2020.27227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585972PMC
September 2020

Adverse health impacts of cooking with kerosene: A multi-country analysis within the Prospective Urban and Rural Epidemiology Study.

Environ Res 2020 09 27;188:109851. Epub 2020 Jun 27.

College of Public Health and Human Sciences, Oregon State University, Corvallis, USA.

Background: Kerosene, which was until recently considered a relatively clean household fuel, is still widely used in low- and middle-income countries for cooking and lighting. However, there is little data on its health effects. We examined cardiorespiratory effects and mortality in households using kerosene as their primary cooking fuel within the Prospective Urban Rural Epidemiology (PURE) study.

Methods: We analyzed baseline and follow-up data on 31,490 individuals from 154 communities in China, India, South Africa, and Tanzania where there was at least 10% kerosene use for cooking at baseline. Baseline comorbidities and health outcomes during follow-up (median 9.4 years) were compared between households with kerosene versus clean (gas or electricity) or solid fuel (biomass and coal) use for cooking. Multi-level marginal regression models adjusted for individual, household, and community level covariates.

Results: Higher rates of prevalent respiratory symptoms (e.g. 34% [95% CI:15-57%] more dyspnea with usual activity, 44% [95% CI: 21-72%] more chronic cough or sputum) and lower lung function (differences in FEV: -46.3 ml (95% CI: -80.5; -12.1) and FVC: -54.7 ml (95% CI: -93.6; -15.8)) were observed at baseline for kerosene compared to clean fuel users. The odds of hypertension was slightly elevated but no associations were observed for blood pressure. Prospectively, kerosene was associated with elevated risks of all-cause (HR: 1.32 (95% CI: 1.14-1.53)) and cardiovascular (HR: 1.34 (95% CI: 1.00-1.80)) mortality, as well as major fatal and incident non-fatal cardiovascular (HR: 1.34 (95% CI: 1.08-1.66)) and respiratory (HR: 1.55 (95% CI: 0.98-2.43)) diseases, compared to clean fuel use. Further, compared to solid fuel users, those using kerosene had 20-47% higher risks for the above outcomes.

Conclusions: Kerosene use for cooking was associated with higher rates of baseline respiratory morbidity and increased risk of mortality and cardiorespiratory outcomes during follow-up when compared to either clean or solid fuels. Replacing kerosene with cleaner-burning fuels for cooking is recommended.
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http://dx.doi.org/10.1016/j.envres.2020.109851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748391PMC
September 2020

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153,152 middle-aged individuals.

Cardiovasc Res 2020 Aug 10. Epub 2020 Aug 10.

Population Health Research Institute, McMaster University, Canada.

Aims: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes.

Methods And Results: Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels.

Conclusions: Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Translational Perspective: We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001); and by as much as 11-fold between groups of countries at different income levels (p < 0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.
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http://dx.doi.org/10.1093/cvr/cvaa241DOI Listing
August 2020

Demographic, behavioral, and cardiovascular disease risk factors in the Saudi population: results from the Prospective Urban Rural Epidemiology study (PURE-Saudi).

BMC Public Health 2020 Aug 8;20(1):1213. Epub 2020 Aug 8.

Population Health Research Institute, DBCVS Research Institute, McMaster University, Hamilton, Canada.

Background: Cardiovascular disease (CVD) is the major cause of death in Saudi Arabia. We aimed to assess associated demographic, behavioral, and CVD risk factors as part of the Prospective Urban Rural Epidemiology (PURE) study.

Methods: PURE is a global cohort study of adults ages 35-70 years in 20 countries. PURE-Saudi study participants were recruited from 19 urban and 6 rural communities randomly selected from the Central province (Riyadh and Alkharj) between February 2012 and January 2015. Data were stratified by age, sex, and urban vs rural and summarized as means and standard deviations for continuous variables and as numbers and percentages for categorical variables. Proportions and means were compared between men and women, among age groups, and between urban and rural areas, using Chi-square test and t-tests, respectively.

Results: The PURE-Saudi study enrolled 2047 participants (mean age, 46.5 ± 9.12 years; 43.1% women; 24.5% rural). Overall, 69.4% had low physical activity, 49.6% obesity, 34.4% unhealthy diet, 32.1% dyslipidemia, 30.3% hypertension, and 25.1% diabetes. In addition, 12.2% were current smokers, 15.4% self-reported feeling sad, 16.9% had a history of periods of stress, 6.8% had permanent stress, 1% had a history of stroke, 0.6% had heart failure, and 2.5% had coronary heart disease (CHD). Compared to women, men were more likely to be current smokers and have diabetes and a history of CHD. Women were more likely to be obese, have central obesity, self-report sadness, experience stress, feel permanent stress, and have low education. Compared to participants in urban areas, those in rural areas had higher rates of diabetes, obesity, and hypertension, and lower rates of unhealthy diet, self-reported sadness, stress (several periods), and permanent stress. Compared to middle-aged and older individuals, younger participants more commonly reported an unhealthy diet, permanent stress, and feeling sad.

Conclusion: These results of the PURE-Saudi study revealed a high prevalence of unhealthy lifestyle and CVD risk factors in the adult Saudi population, with higher rates in rural vs urban areas. National public awareness programs and multi-faceted healthcare policy changes are urgently needed to reduce the future burden of CVD risk and mortality.
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http://dx.doi.org/10.1186/s12889-020-09298-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414714PMC
August 2020

Associations of outdoor fine particulate air pollution and cardiovascular disease in 157 436 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Lancet Planet Health 2020 06;4(6):e235-e245

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.

Background: Most studies of long-term exposure to outdoor fine particulate matter (PM) and cardiovascular disease are from high-income countries with relatively low PM concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM 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 PM 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 PM 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 PM 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 PM at cohort baseline was 47·5 μg/m (range 6-140). In models adjusted for individual, household, and geographical factors, a 10 μg/m increase in PM 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 PM concentrations (>35 μg/m). The population attributable fraction for PM 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 PM and risk for non-cardiovascular disease deaths.

Interpretation: Long-term outdoor PM 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).
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http://dx.doi.org/10.1016/S2542-5196(20)30103-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457447PMC
June 2020

Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.

JAMA Psychiatry 2020 10;77(10):1052-1063

Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live.

Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas.

Design, Setting, And Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019.

Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview.

Main Outcomes And Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality.

Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001).

Conclusions And Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.1351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287938PMC
October 2020

Self-Reported Prevalence of Chronic Non-Communicable Diseases in Relation to Socioeconomic and Educational Factors in Colombia: A Community-Based Study in 11 Departments.

Glob Heart 2020 04 21;15(1):35. Epub 2020 Apr 21.

Fundación Oftalmológica de Santander-FOSCAL, Floridablanca, CO.

Background: Chronic non-communicable diseases are prevalent conditions in developing countries, such as Colombia. Several socioeconomic and educational factors have been associated with these pathologies. However, there is little country-specific information regarding the self-reported prevalence of chronic diseases and their association with the aforementioned factors in Colombia.

Objectives: To evaluate the current situation of chronic non-transmissible diseases in Colombia by self-report and to analyze its potential relationship with sociodemographic, economic and educational factors.

Methods: This is a cross-sectional baseline sub-analysis from the prospective, standardized collaborative PURE study in Colombia. Participants were recruited between 2005 to 2009, in 11 departments of the country, and included 7,485 subjects of 35 to 70 years old. Questionnaires of self-reported chronic non-communicable diseases, and demographic, socioeconomic and educational variables were applied.

Results: Hypertension was the most prevalent chronic condition reported with a prevalence of 22.2% (21.2%-23.1%, 95% CI), followed by diabetes with a prevalence of 5.7% (5.1%-6.2%, 95% CI), asthma 2.7% (2.2%-3.0%, 95% CI), coronary heart disease 2.4% (2.0%-2.7%, 95% CI), stroke and heart failure 1.5% (1.2%-1.8%, 95% CI) each, chronic obstructive pulmonary disease 1.2% (0.6%-1.5%, 95% CI), and cancer 1.2% (1.0%-1.5%, 95% CI). Among the study sample, 23.3% (22.4%-24.3%, 95% CI) reported having one chronic NCDs, and 6.4% (5.9%-7.0%, 95% CI) reported having multiple chronic NCDs. The prevalence of multiple NCDs increased significantly with age, was more common in those from households with higher income, whereas it was significantly lower in persons with high education.The central and central-east regions of the country are those with the higher prevalence of self-reported NCDs.

Conclusion: The results of the current study indicate the presence of socioeconomic and educational inequalities in the distribution of chronic NCDs in the Colombian population.
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http://dx.doi.org/10.5334/gh.792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218792PMC
April 2020

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

Am Heart J 2020 07 25;225:69-77. Epub 2020 Mar 25.

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

Background: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need.

Methods: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm, left atrial spontaneous echo-contrast or thrombus, or a CHADSVASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD.

Conclusion: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.
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http://dx.doi.org/10.1016/j.ahj.2020.03.018DOI Listing
July 2020

Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Lancet 2020 07 20;396(10244):97-109. Epub 2020 May 20.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Background: Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies.

Methods: In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.

Findings: From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.

Interpretation: Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.

Funding: Full funding sources are listed at the end of the paper (see Acknowledgments).
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http://dx.doi.org/10.1016/S0140-6736(20)30543-2DOI Listing
July 2020

Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study.

Am J Clin Nutr 2020 07;112(1):208-219

Population Health Research Institute, Hamilton, ON, Canada.

Background: The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries.

Objective: To assess the association of nuts with mortality and cardiovascular disease (CVD).

Methods: The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35-70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure].

Results: We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with <30 g per mo) was associated with a lower risk of the primary composite outcome of mortality or major cardiovascular event [multivariate HR (mvHR): 0.88; 95% CI: 0.80, 0.96; P-trend = 0.0048]. Significant reductions in total (mvHR: 0.77; 95% CI: 0.69, 0.87; P-trend <0.0001), cardiovascular (mvHR: 0.72; 95% CI: 0.56, 0.92; P-trend = 0.048), and noncardiovascular mortality (mvHR: 0.82; 95% CI: 0.70, 0.96; P-trend = 0.0046) with a trend to reduced cancer mortality (mvHR: 0.81; 95% CI: 0.65, 1.00; P-trend = 0.081) were observed. No significant associations of nuts were seen with major CVD (mvHR: 0.91; 95% CI: 0.81, 1.02; P-trend = 0.14), stroke (mvHR: 0.98; 95% CI: 0.84, 1.14; P-trend = 0.76), or MI (mvHR: 0.86; 95% CI: 0.72, 1.04; P-trend = 0.29).

Conclusions: Higher nut intake was associated with lower mortality risk from both cardiovascular and noncardiovascular causes in low-, middle-, and high-income countries.
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http://dx.doi.org/10.1093/ajcn/nqaa108DOI Listing
July 2020

Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries.

BMJ Open Diabetes Res Care 2020 04;8(1)

Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.

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 , 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 , 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 of MetS and most of its component factors, and with a 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.
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http://dx.doi.org/10.1136/bmjdrc-2019-000826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326257PMC
April 2020

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

Environ Pollut 2020 Jul 24;262:114197. Epub 2020 Feb 24.

School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.

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 PM and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM 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 PM exposure ranged from 3 to 97 μg/m 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/m increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM > 62 μg/m) compared to the first (PM < 14 μg/m) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (β = 2.15 mmHg, 95% CI: -0.59, 4.89) and diastolic BP (β = 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 PM was associated with increased BP and hypertension while there were small inverse associations with HAP.
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http://dx.doi.org/10.1016/j.envpol.2020.114197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767575PMC
July 2020

Variations in incidence of venous thromboembolism in low-, middle-, and high-income countries.

Cardiovasc Res 2021 Jan;117(2):576-584

Population Health Research Institute, DBCVSRI, Hamilton General Hospital, 237 Barton St. East, Hamilton, ON L8L 2X2, Canada.

Aims: To examine the rates of venous thromboembolism (VTE) in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification).

Methods And Results: We examined the rates of VTE in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, and COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis, and thrombophlebitis. We calculated age- and sex-standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215 307 individuals (1.5 million person-years of follow-up) from high-income (n = 60 403), upper middle-income (n = 42 066), and lower middle/low-income (n = 112 838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle-, and lower middle/low-income countries were 0.87, 0.25, and 0.06, respectively. After adjusting for age, body mass index (BMI), smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries [hazard ratio (HR) 3.57, 95% confidence interval (CI) 2.40-5.30 and HR 2.27, 95% CI 1.59-3.23, respectively]. The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-White ethnicity, and higher education.

Conclusion: The rates of VTE are substantially higher in high-income than in low-income countries. The factors underlying the increased VTE risk in higher-income countries remain unknown.
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http://dx.doi.org/10.1093/cvr/cvaa044DOI Listing
January 2021

The household economic burden of non-communicable diseases in 18 countries.

BMJ Glob Health 2020 11;5(2):e002040. Epub 2020 Feb 11.

London School of Hygiene and Tropical Medicine Faculty of Public Health and Policy, London, UK.

Background: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries.

Methods: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China.

Results: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs.

Conclusions: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs.
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http://dx.doi.org/10.1136/bmjgh-2019-002040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042605PMC
February 2020