Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

BACKGROUND: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. METHODS: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. FINDINGS: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. INTERPRETATION: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Lifestyle factors associated with the transition from healthy to unhealthy adiposity among black South African adults over 10 years.

BACKGROUND AND AIMS: Obesity is associated with an increasing prevalence of cardiovascular diseases in Africa, but some obese individuals maintain cardiometabolic health. The aims were to track metabolically healthy overweight or obesity (MHO) over 10 years in African adults and to identify factors associated with a transition to metabolically unhealthy overweight or obesity (MUO). METHODS AND RESULTS: The participants were the South African cohort of the international Prospective Urban and Rural Epidemiological study. From the baseline data of 1937 adults, 649 women and 274 men were followed for 10 years. The combined overweight and obesity prevalence of men (19.2%-23.8%, p = .02) and women (58%-64.7%, p < .001), and the prevalence of the metabolic syndrome in all participants (25.4%-40.2%, p < .001) increased significantly. More than a quarter (26.2%) of the women and 10.9% of men were MHO at baseline, 11.4% of women and 5.1% of men maintained MHO over 10 years, while similar proportions (12.3% of women, 4.7% of men) transitioned to MUO. Female sex, age, and total fat intake were positively associated with a transition to MUO over 10 years, while physical activity was negatively associated with the transition. HIV positive participants were more likely to be MHO at follow-up than their HIV negative counterparts. CONCLUSIONS: One in two black adults with BMI ≥25 kg/m2 maintained MHO over 10 years, while a similar proportion transitioned into MUO. Interventions should focus on lower fat intakes and higher physical activity to prevent the transition to MUO.

The association between anthropometric measures and physical performance in black adults of the North West Province, South Africa.

OBJECTIVE: This study investigated associations between anthropometric measures and physical performance in black South African adults. It was hypothesized that noninvasive, simple anthropometric measurements, such as calf circumference (CC) and body mass index (BMI), may be useful predictors of physical performance and strength. METHODS: Black human immunodeficiency virus (HIV) negative men and women (aged 32-93 years) participating in the Prospective Urban and Rural Epidemiology (PURE) study were enrolled at baseline in 2005 = 1428). Men and women's anthropometry, socio-demographics and physical activity (PA) were assessed at baseline, 5- and 10-year follow-up. Physical performance (walk speed, chair stand and handgrip strength [HGS]) were assessed at 10-year follow-up. Linear regression models adjusted for potential confounders were used to evaluate the association between anthropometric measures and physical performance. RESULTS: The combined overweight and obesity prevalence among both men (P = .02) and women (P < .001) increased significantly over 10 years, with significant increases over time in BMI and CC in the women, whereas PA decreased significantly over time in both men and women (P < .0001). BMI and CC were positively associated with HGS in the men (P = .02, P < .0001) and women (P < .0001), while CC was positively associated with walk speed in men only (P = .006) in the cross-sectional analysis of 2015 measurements. CONCLUSION: BMI and CC in both men and women were positively associated with HGS, but CC was associated with walk speed in the men only. Our study suggests that CC may be a useful predictor of physical performance in black men and to a limited extent in black women.

Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults.

BACKGROUND: The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated. METHODS: Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression. RESULTS: Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (ß per 1 SD: - 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (ß (95% confidence interval): - 0.25 (- 0.31, - 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality. CONCLUSION: Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function. TRIAL REGISTRATION: PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).

Coverage and factors associated with vitamin A supplementation among children aged 6-59 months in twenty-three sub-Saharan African countries.

OBJECTIVE: The present study aimed to give an overall view of the pattern of high-dose vitamin A supplementation (VAS) coverage in twenty-three sub-Saharan African countries and factors associated with receipt of VAS among children aged 6-59 months. DESIGN: Cross-sectional data from the twenty-three Demographic and Health Surveys conducted from 2011 to 2015 in twenty-three sub-Saharan African countries were pooled. A multilevel logistic regression model was used to explore factors associated with VAS. SETTING: Twenty-three sub-Saharan African countries.ParticipantsChildren (n 215 511) aged 6-59 months. RESULTS: The overall coverage of VAS among children aged 6-59 months for the surveys included was 59·4 %. In the multivariable analysis, children whose mothers had primary (adjusted OR (aOR)=1·43; 95 % CI 1·39, 1·47) or secondary or above (aOR=1·72; 95 % CI 1·67, 1·77) educational status were more likely to receive VAS than children whose mothers had no formal education. Other factors associated with significantly increased likelihood of VAS were: living in urban areas; children of working mothers; children whose mothers had higher media exposure; children of older mothers v. children of mothers aged 15-19 years; and older children v. children aged 6-11 months. At the country level, lower media exposure was significant and negatively associated with VAS. CONCLUSIONS: Broader VAS coverage is needed according to our data. More efforts are needed to scale up coverage, focusing mostly on groups at risk of non-receipt of vitamin A.

A Pilot Investigation of the Association Between Vpr Amino Acid Substitutions and Peripheral Immune Marker Levels in People With Human Immunodeficiency Virus: Implications for Neurocognitive Impairment.

Background: Subtype-specific amino acid variations in viral proteins of human immunodeficiency virus type 1 (HIV-1) influence disease progression. Furthermore, Vpr sequence variation correlates with chronic inflammation, a central mechanism in HIV-1 (neuro)pathogenesis. Nevertheless, no clinical study has investigated the link between Vpr sequence variation and peripheral inflammation in people with HIV (PWH). The aim of this pilot study was to ascertain whether specific Vpr amino acid variants were associated with immune markers in PWH. Methods: We included a unique cohort of 48 treatment-naive South African PWH to determine the association between blood-derived Vpr sequence variation and peripheral immune marker levels using Sanger sequencing and enzyme-linked immunosorbent assay analysis, respectively. Results: Our findings indicate that among the many neuropathogenic Vpr amino acid variants and immune markers examined, after applying Bonferroni corrections (P = .05/3) and adjusting for sex and locality, soluble urokinase plasminogen activator receptor (suPAR) was nearing significance for higher levels in participants with the G41 amino acid variant compared to those with the S41 variant (P = .035). Furthermore, amino acid variations at position 41 (between G41 and S41) exhibited a significant association with suPAR (adjusted R2 = 0.089, ß = .386 [95% confidence interval, .125-3.251]; P = .035). Conclusions: These findings suggest that Vpr amino acid sequence variations might contribute to dysregulated inflammation, which could explain the observed association between specific Vpr variants and HIV-1 (neuro)pathogenesis found in prior research. These Vpr variants merit further investigation to fully understand their roles in HIV-1 pathogenesis and neuropathogenesis.

Noncommunicable Disease Conditions and HIV in Rural and Urban South Africa: 2005-2015.

Purpose: Hypertension, obesity, hyperlipidemia, and type 2 diabetes contribute primarily to noncommunicable disease deaths and together with human immunodeficiency virus contribute largely to mortality in South Africa. Our longitudinal study provides the necessary data and insights over a 10-year period to highlight the areas where improved management is required in urban and rural localities. Methods: This study included 536 rural and 387 urban Black participants aged 32 to 93 years from the North-West province, South Africa. Disease prevalence, treatment, and control were determined in 2005 and were re-evaluated in 2015. Multiple measures analyses were used to determine the trends of blood pressure and waist circumference. Results: The initial prevalence of hypertension was 53.2%, obesity was 23.6%, hyperlipidemia was 5.1%, diabetes was 2.9%, and human immunodeficiency virus was 10.7% in 2005. By 2015, the rural population had higher rates of hypertension (63.7% versus 58.5%) and lower rates diabetes (4.3% versus 7.9%) and hyperlipidemia (6.6% versus 18.0%) with similar obesity rates (41.7% versus 42.4%). The average blood pressure levels of urban hypertensives decreased (Ptrend<.001), whereas levels were maintained in the rural group (Ptrend=.52). In both locations, treatment and control rates increased from 2005 to 2015 for all conditions (all ≥6.7%), except for diabetes in which a decrease in control was observed. Waist circumference increased (Ptrend>.001) in both sex and locality groups over the 10-year period. Conclusion: Although average blood pressure of urban hypertensive individuals decreased, urgent measures focused on early identification, treatment, and control of the respective conditions should be implemented to decrease the burden of noncommunicable diseases.

Strategies of Modelling Incident Outcomes Using Cox Regression to Estimate the Population Attributable Risk.

When the Cox model is applied, some recommendations about the choice of the time metric and the model's structure are often disregarded along with the proportionality of risk assumption. Moreover, most of the published studies fail to frame the real impact of a risk factor in the target population. Our aim was to show how modelling strategies affected Cox model assumptions. Furthermore, we showed how the Cox modelling strategies affected the population attributable risk (PAR). Our work is based on data collected in the North-West Province, one of the two PURE study centres in South Africa. The Cox model was used to estimate the hazard ratio (HR) of mortality for all causes in relation to smoking, alcohol use, physical inactivity, and hypertension. Firstly, we used a Cox model with time to event as the underlying time variable. Secondly, we used a Cox model with age to event as the underlying time variable. Finally, the second model was implemented with age classes and sex as strata variables. Mutually adjusted models were also investigated. A statistical test to the multiplicative interaction term the exposures and the log transformed time to event metric was used to assess the proportionality of risk assumption. The model's fitting was investigated by means of the Akaike Information Criteria (AIC). Models with age as the underlying time variable with age and sex as strata variables had enhanced validity of the risk proportionality assumption and better fitting. The PAR for a specific modifiable risk factor can be defined more accurately in mutually adjusted models allowing better public health decisions. This is not necessarily true when correlated modifiable risk factors are considered.

Comparing estimates of household expenditures between pictorial diaries and surveys in three low- and middle-income countries.

In most low- and middle-income countries (LMICs), household out-of-pocket (OOP) health spending constitutes a major source of healthcare financing. Household surveys are commonly used to monitor OOP health spending, but are prone to recall bias and unable to capture seasonal variation, and may underestimate expenditure-particularly among households with long-term chronic health conditions. Household expenditure diaries have been developed as an alternative to overcome the limitations of surveys, and pictorial diaries have been proposed where literacy levels may render traditional diary approaches inappropriate. This study compares estimates for general household and chronic healthcare expenditure in South Africa, Tanzania and Zimbabwe derived using survey and pictorial diary approaches. We selected a random sub-sample of 900 households across urban and rural communities participating in the Prospective Urban and Rural Epidemiology study. For a range of general and health-specific categories, OOP expenditure estimates use cross-sectional survey data collected via standardised questionnaire, and data from these same households collected via two-week pictorial diaries repeated four times over 2016-2019. In all countries, average monthly per capita expenditure on food, non-food/non-health items, health, and consequently, total household expenditure reported by pictorial diaries was consistently higher than that reported by surveys (each p<0.001). Differences were greatest for health expenditure. The share of total household expenditure allocated to health also differed by method, accounting for 2% in each country when using survey data, and from 8-20% when using diary data. Our findings suggest that the choice of data collection method may have significant implications for estimating OOP health spending and the burden it places on households. Despite several practical challenges to their implementation, pictorial diaries offer a method to assess potential bias in surveys or triangulate data from multiple sources. We offer some practical guidance when considering the use of pictorial diaries for estimating household expenditure.

Associations Between 25-Hydroxyvitamin D and Total and γ' Fibrinogen and Plasma Clot Properties and Gene Interactions in a Group of Healthy Black South African Women.

The role of 25-hydroxyvitamin D [25(OH)D] in reducing the risk of cardiovascular disease (CVD) has been recognized, but the mechanisms involved are unclear. Researchers have discovered a link between vitamin D and fibrinogen. Until now, data on the relationship between vitamin D and the γ' splice variant of fibrinogen and fibrin clot characteristics remain unexplored. In this study, 25(OH)D, total and γ' fibrinogen, as well as turbidimetrically determined plasma clot properties, were quantified, and fibrinogen and FXIII SNPs were genotyped in 660 Black, apparently healthy South African women. Alarmingly, 16 and 45% of the women presented with deficient and insufficient 25(OH)D, respectively. Total fibrinogen and maximum absorbance (as a measure of clot density) correlated inversely, whereas γ' fibrinogen correlated positively with 25(OH)D. γ' fibrinogen increased whereas maximum absorbance decreased over the deficient, insufficient, and sufficient 25(OH)D categories before and after adjustment for confounders. 25(OH)D modulated the association of the SNPs regarding fibrinogen concentration and clot structure/properties, but did not stand after correction for false discovery rate. Because only weak relationships were detected, the clinical significance of the findings are questionable and remain to be determined. However, we recommend vitamin D fortification and supplementation to reduce the high prevalence of this micronutrient deficiency and possibly to improve fibrinogen and plasma clot structure if the relationships are indeed clinically significant. There is a need for large cohort studies to demonstrate the relationship between vitamin D and cardiovascular and inflammatory risk factors as well as to uncover the molecular mechanisms responsible.

Prognostic values of modifiable risk factors for cardiovascular events in South African health promotion.

BACKGROUND: Cardiovascular diseases (CVDs) are increasing at an alarming rate among the South African population. This study aimed to determine the prognostic value of modifiable CVD risk factors for fatal and non-fatal events to inform cardiovascular health promotion practices in the South African public health system. METHODS: Data was collected from individuals participating in the South African leg of a multi-national prospective cohort study. Binary logistic regression was applied to estimate odds of total, non-fatal and fatal cardiovascular events. RESULTS: Binary logistic regression analyses identified age as a predictor of non-fatal and fatal CV events, with ORs of 1.87 to 3.21, respectively. Hypertension increased the odd of suffering a non-fatal CV event by almost two and a half (OR = 2.47; 95% CI = 1.26, 4.85). Moreover, being physically active reduced the odd of non-fatal CVD events by 38% (OR = 0.62; 95% CI = 0.46, 0.83 for 1 Standard deviation increase of the weighted physical activity index score (WPA)). On the one hand, gamma-glutamyltransferase (GGT) was associated with a higher fatal cardiovascular disease risk OR = 2.45 (95% CI = 1.36, 4.42) for a standard deviation increase. CONCLUSIONS: Elevated blood pressure, GGT, and physical activity have significant prognostic values for fatal or non-fatal CV events. These findings emphasise the importance of highlighting hypertension and physical activity when planning cardiovascular health education and intervention programmes for this population, with attention to the monitoring of GGT.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis.

BACKGROUND: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. METHODS: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. FINDINGS: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88-2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69-19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. INTERPRETATION: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. FUNDING: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre.

Variations in the association of height with mortality, cardiovascular disease and cancer in low-, middle- and high-income countries.

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.

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

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.

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

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

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

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

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

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.

Is the cardiovascular health of South Africans today comparable with African Americans 45 years ago?

OBJECTIVES: Hypertension occurs frequently among black populations around the world. In the United States (US) health system, interventions since the 1960s resulted in improvements in hypertension awareness, management and control among African Americans. This is in stark contrast to current health systems in African countries. To objectively assess the current situation in South Africa, we compared the cardiovascular health status of African Americans from 1960 to 1980 to black South Africans from recent years, as there is potential to implement best practices from the US. We also reviewed the recent cardiovascular health changes of a South African population over 10 years. METHODS: Men and women were included from three studies performed in the United States (Evans County Heart Study; Charleston Heart Study; NHANES I and II) and one in South Africa (PURE, North West Province). We compared blood pressure (BP), BMI, cholesterol, diabetes and smoking status. RESULTS: Age-adjusted SBP and DBP of South African men were lower than US studies conducted from 1960 to 1971 (Evans County; Charleston; NHANES I; all P < 0.001) but similar to NHANES II (P = 0.987) conducted in 1976. South African women had lower SBP than all four of the US studies (all P < 0.001); their DBP was lower than Evans County and Charleston studies, but similar to NHANES I and II. Reviewing South African data, BMI increased steeply over 10 years in women (P < 0.001) but not men (P = 0.451). CONCLUSION: Blood pressure of South Africans is lower than African Americans from the 1960s, but comparable for 1970s to 1980s. With obesity of South African women rising sharply, escalating figures for hypertension and diabetes are anticipated.

Magnesium Intake Predicts Bone Turnover in Postmenopausal Black South African Women.

This prospective study investigated the association between nutrient intake, dietary patterns, and changes in bone turnover and bone mineral density (BMD) in postmenopausal urban black South African women over two years. These women (n = 144) underwent BMD measurements at the distal radius, lumbar spine, femoral neck (FN), as well as a biochemical analysis which included the parathyroid hormone (PTH), 25-hydroxyvitamin D, C-Telopeptide of type I collagen (CTX-1) in 2010 and 2012. Their dietary intake was assessed in 2010 using a food frequency questionnaire, and sociodemographic and health information was collected. Four dietary patterns explained 54.4% of the variance of dietary intake, namely staple foods and processed meats, home cooking, snacking, and high sugar. Dietary magnesium negatively correlated with CTx-1 in 2012 (r = -0.21, p = 0.02), calcium correlated with distal radius BMD in 2010 (r = 0.22, p = 0.01) and 2012 (r = 0.24, p = 0.005), and the snacking dietary pattern score correlated with FN BMD in 2010 (r = 0.18, p = 0.03) and 2012 (r = 0.21, p = 0.02). The baseline CTx-1 and dietary magnesium intake predicted 22% of the variance in percentage change of CTx-1 over two years (p < 0.001).The magnesium intake predicted short-term bone resorption over two years.