Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Triglyceride-glucose index, low-density lipoprotein levels, and cardiovascular outcomes in chronic stable cardiovascular disease: results from the ONTARGET and TRANSCEND trials.

AIMS: The triglyceride-glucose index (TyG) has been proposed as an alternative to insulin resistance and as a predictor of cardiovascular outcomes. Little is known on its role in chronic stable cardiovascular disease and its predictive power at controlled low density lipoprotein (LDL) levels. METHODS AND RESULTS: Our study population consisted of 29 960 participants in the ONTARGET and TRANSCEND trials that enrolled patients with known atherosclerotic disease. Triglycerides and glucose were measured at baseline. TyG was calculated as the logarithmized product of fasting triglycerides and glucose divided by 2. The primary endpoint of both trials was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The secondary endpoint was all-cause death and the components of the primary endpoint. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) with extensive covariate adjustment for demographic, medical history, and lifestyle factors. During a mean follow-up of 4.3 years, 4895 primary endpoints and 3571 all-cause deaths occurred. In fully adjusted models, individuals in the highest compared to the lowest quartile of the TyG index were at higher risk for the primary endpoint (HR 1.14; 95% CI 1.05-1.25) and for myocardial infarction (HR 1.30; 95% CI 1.11-1.53). A higher TyG index did not associate with the primary endpoint in individuals with LDL levels < 100 mg/dL. CONCLUSION: A higher TyG index is associated with a modestly increased cardiovascular risk in chronic stable cardiovascular disease. This association is largely attenuated when LDL levels are controlled. REGISTRATION: www.clinicaltrials.gov: NCT00153101.

The association of triglyceride-glucose index (TyG) with cardiovascular disease in chronic stable cardiovascular disease and its predictive power at controlled low density lipoprotein (LDL) levels is unclear. Using a study population of 29 960 participants with chronic stable cardiovascular disease, we found that higher TyG levels were associated with a modestly increased risk for incident cardiovascular events and low LDL levels largely attenuated the association of TyG with cardiovascular risk.

Association between impaired lung function and carotid intima-media thickness in children.

Association between obstructive lung function impairment with higher cIMT is present in childhood after accounting for common risk factors. This suggests that a developmental link between obstructive lung diseases and CVD may have its origin in early life. https://bit.ly/4657s2b.

Individual- and supply-level macronutrient intakes are well correlated over a 50-year period (1961-2011) in 18 countries in Asia, North America, and Europe.

Reliable information on dietary trends is essential. We compared individual-level dietary estimates for total energy, carbohydrate, fat, and protein intake over time with national supply data from the Global Expanded Nutrient Supply Model (186 paired estimates from 1961 to 2011, 18 countries). We hypothesized that supply data would overestimate individual measures and that the two measures would be weakly correlated. Individual- and supply-level estimates were compared using Spearman correlation coefficients and linear mixed-effect models were used to estimate the differences between measures. Overall, the correlations between individual- and supply-level measures were moderate for energy (rs = 0.34) and carbohydrate (rs = 0.39), strong for fat (rs = 0.85), and protein (rs = 0.69). Trends in total energy measured by individual-level surveys and total energy supply were positively correlated in 38.9% of countries, whereas trends in macronutrients aligned between estimates in most countries. Supply-level dietary data overestimated individual-level intakes, especially in higher income countries in Europe and in the United States. In the United States, supply-level data exceeded individual-level estimates by 26.3% to 29.9% for energy, carbohydrate, and fat, whereas protein estimates were similar between measures. In Europe, supply-level estimates overestimated individual-level intake by 19.9% for energy, 17.0% for carbohydrate, 13.7% for fat, and 7.7% for protein, whereas estimates for energy and macronutrients were similar in Asia. In Asia and lower income countries, our findings generally support the use of supply-level data in the absence of individual-level data, though this finding may be related to smaller sample size and differences in underlying national statistics that inform supply data.

Sex-Specific Effects of Blood Pressure Lowering Pharmacotherapy for the Prevention of Cardiovascular Disease: An Individual Participant-Level Data Meta-Analysis.

BACKGROUND: Whether the relative effects of blood pressure (BP)-lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain. METHODS: We conducted an individual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. RESULTS: We included data from 51 randomized controlled trials involving 358 636 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89-0.95] for women and 0.90 [0.88-0.93] for men; P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14). CONCLUSIONS: The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

Integrative multiomics analysis of infant gut microbiome and serum metabolome reveals key molecular biomarkers of early onset childhood obesity.

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.

Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis.

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.

Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression.

Aims: Elevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown. Methods and results: We investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study (n = 18 226, 406 incident cases) and the UK Biobank (n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study (n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (<50 mg/dL) and low CRP levels (<2.0 mg/L), those with elevated Lp(a) (>50 mg/dL) and low CRP levels (<2.0 mg/L) and those with elevated Lp(a) (>50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30-2.67) and 2.08 (1.44-2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels. Conclusion: Lp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation.

Validation of Urinary Thiocyanate as a Robust Biomarker of Active Tobacco Smoking in the Prospective Urban and Rural Epidemiological Study.

INTRODUCTION: Tobacco smoking is a leading preventable cause of premature death globally. Urinary thiocyanate is a biomarker of cyanide exposure from tobacco smoke; however, few studies have evaluated its utility in diverse populations of smokers. AIMS AND METHODS: We examined the associations between urinary thiocyanate and self-reported never and current smokers among 1000 participants from 14 countries in the Prospective Urban and Rural Epidemiological study. We analyzed urinary thiocyanate in light and heavy smokers as compared to never-smokers from high- (HICs), middle- (MICs), and low-income countries (LICs) using a validated capillary electrophoresis method in conjunction with standardized questionnaires. RESULTS: The median urinary thiocyanate concentration was 31 µM, which ranged from 8.6 µM to 52 µM for never-smokers (n = 335) and current smokers (n = 660), respectively. Urinary thiocyanate was correlated with daily cigarette consumption (r = 0.621) and total nicotine equivalents (r = 0.514). Thiocyanate also displayed a better dose-response than urinary cotinine. A moderate association of urinary thiocyanate was found in biochemically verified never-smokers (r ~0.38) because of intake of vegetables, fruits, and dairy. Receiver-operating characteristic curves established cutoff values for urinary thiocyanate to differentiate current from never-smokers with an optimal threshold of 23.9 µM (Area Under the Curve or AUC = 0.861), which lowered progressively from HICs, MICs, and LICs. CONCLUSIONS: Elevated thiocyanate was evident in current smokers from high-income countries likely reflecting differences in smoking topography and greater toxicant burden. Background urinary thiocyanate in never-smokers was associated with goitrogenic food intake that obscured detection of secondhand smoke exposure. IMPLICATIONS: Urinary thiocyanate is a sensitive biomarker of active tobacco smoking relative to cotinine that can be measured by an inexpensive capillary electrophoresis assay. Regional cutoff values are demonstrated to improve discrimination of smoking status in developing countries because of differences in smoking habits and cigarette products consumed, as well as intake of goitrogenic foods. Urinary thiocyanate may allow for more reliable estimates of the hazards of tobacco smoking between countries with varying socioeconomic development as compared to self-reports.

Changes in energy, macronutrient, and food consumption in 47 countries over the last 70 years (1950-2019): a systematic review and meta-analysis.

OBJECTIVES: We aimed to systematically examine trends in dietary energy, macronutrient, and food consumption in different geographic regions. METHODS: We searched Medline, Embase, CINAHL, and organizations for studies and reports using individual-level dietary assessments from 1950 to 2019 (PROSPERO CRD42022302843) and quantified changes using multivariable linear mixed-effects models. RESULTS: We identified 109 articles and reports from 47 countries, including Europe and Australasia (47% of studies), Asia (30%), Latin America (13%), the Middle East (6%), and North America (4%). In Southeast and East Asia, carbohydrate intake decreased, whereas fat consumption increased; the opposite pattern occurred in North America; and fat decreased while carbohydrate intake remained stable in Europe and Australasia. Consumption of carbohydrate and fat were stable in South Asia, Latin America, and the Middle East, but data were limited in these regions. A greater increase in national gross domestic product over time was associated with decreased carbohydrate and increased fat and protein intake. Dietary saturated fatty acid intake decreased in Northern and Eastern Europe and was stable in other regions. Changes in food varied by region; East and Southeast Asia increased meat, fish, dairy, egg, fruit, and vegetable consumption and decreased intake of grains, roots and tubers, legumes, whereas North America decreased dairy and red meat but increased eggs, nuts, poultry, and vegetable oil intake. Intakes of fruits, nuts, legumes, and roots and tubers were below recommendations in most regions. CONCLUSIONS: Our findings indicate regional variations in dietary trends and identify countries that would benefit from nutritional policies aimed at decreasing lower-quality carbohydrate foods and increasing consumption of fruits, vegetables, nuts, legumes, and dairy.

The association of maternal sugary beverage consumption during pregnancy and the early years with childhood sugary beverage consumption.

OBJECTIVES: A woman's food choices during pregnancy may be associated with her offspring's food choices. Several studies support an association between childhood sugary beverage (SB) consumption and poor cardiometabolic health. This study aimed to assess the association of maternal SB consumption during pregnancy and later, with her offspring's SB consumption in early infancy and childhood. METHODS: A total of 1945 women and 1595 children participating in 3 Canadian studies reported SB consumption during pregnancy, at 2 years of age, and/or at school age (5 to 8 years old). Mother and offspring SB intakes were self-reported by mothers. Multivariable linear regression analyses were conducted within each cohort and cohort data were combined using fixed effect meta-analyses. RESULTS: Maternal SB consumption during pregnancy was associated with higher offspring SB consumption at 2 years of age (standardized ß = 0.19 predicted change in the number of standard deviations of offspring SB intake for an increase of 1 standard deviation in maternal serving [95% CI: 0.16 to 0.22]). Concurrent maternal SB consumption was associated with higher offspring SB intake when children were aged 5 to 8 years (standardized ß= 0.25 [95% CI: 0.10 to 0.40]). CONCLUSION: Maternal SB consumption during pregnancy is associated with a marginally higher SB intake among their offspring at age 2, and concurrent maternal consumption is associated with a higher SB intake among school-aged offspring (5 to 8 years old). Future interventions tailored for pregnancy and early childrearing years to reduce SB intakes of mothers may reduce young children's SB intake.

RéSUMé: OBJECTIFS: Il peut y avoir un lien entre les choix alimentaires d'une femme pendant la grossesse et ceux de son enfant. Plusieurs études font état d'une association entre la consommation de boissons sucrées (BS) durant l'enfance et la mauvaise santé cardiométabolique. Notre étude visait à évaluer l'association entre la consommation de BS des mères pendant et après la grossesse et la consommation de BS de leurs enfants durant la petite enfance et l'enfance. MéTHODE: En tout, 1 945 femmes et 1 595 enfants participant à 3 études canadiennes ont fait état de leur consommation de BS pendant la grossesse, à l'âge de 2 ans et/ou à l'âge scolaire (5 à 8 ans). La consommation de BS des mères et des enfants a été déclarée par les mères. Des analyses de régression linéaire multivariée ont été menées dans chaque cohorte, et les données des cohortes ont été combinées à l'aide de méta-analyses à effets fixes. RéSULTATS: La consommation maternelle de BS pendant la grossesse était associée à une consommation de BS plus élevée chez les enfants à l'âge de 2 ans (le coefficient ß standardisé = 0,19 prédisait le changement du nombre d'écart-types de consommation de BS chez les enfants pour chaque hausse de 1 écart-type de la portion maternelle [IC de 95 % : 0,16 à 0,22]). La consommation maternelle concomitante de BS était associée à une consommation de BS plus élevée chez les enfants lorsqu'ils étaient âgés de 5 à 8 ans (coefficient ß standardisé = 0,25 [IC de 95 % : 0,10 à 0,40]). CONCLUSION: La consommation maternelle de BS pendant la grossesse est associée à une consommation de BS marginalement plus élevée chez l'enfant à l'âge de 2 ans, et la consommation maternelle concomitante est associée à une consommation de BS plus élevée chez l'enfant d'âge scolaire (5 à 8 ans). De futures interventions visant à réduire la consommation de BS des mères pendant la grossesse et durant les premières années où elles élèvent leurs enfants pourraient réduire la consommation de BS des jeunes enfants.

Hypertension management in patients with cardiovascular comorbidities.

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin-angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis.

BACKGROUND: Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. METHODS: We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, ß blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. FINDINGS: We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. INTERPRETATION: Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. FUNDING: British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

The Prevalence and Risk Factors Associated with Iodine Deficiency in Canadian Adults.

Iodine is a trace micronutrient that is critical for normal thyroid function and human health. Inadequate dietary intake is associated with cognitive impairment, infertility, growth retardation and iodine deficiency disorders in affected populations. Herein, we examined the prevalence of iodine deficiency in adults (median age of 61 years) based on the analysis of 24 h urine samples collected from 800 participants in four clinical sites across Canada in the Prospective Urban and Rural Epidemiological (PURE) study. Urinary iodide together with thiocyanate and nitrate were measured using a validated capillary electrophoresis assay. Protective/risk factors associated with iodine deficiency were identified using a binary logistic regression model, whereas daily urinary iodine concentration (24 h UIC, µg/L) and urinary iodine excretion (24 h UIE, µg/day) were compared using complementary statistical methods with covariate adjustments. Overall, our Canadian adult cohort had adequate iodine status as reflected by a median UIC of 111 µg/L with 11.9% of the population <50 µg/L categorized as having moderate to severe iodine deficiency. Iodine adequacy was also evident with a median 24 h UIE of 226 µg/day as a more robust metric of iodine status with an estimated average requirement (EAR) of 7.1% (< 95 µg/day) and a tolerable upper level (UL) of 1.8% (≥1100 µg/day) based on Canadian dietary reference intake values. Participants taking iodine supplements (OR = 0.18; p = 6.35 × 10−5), had greater 24 h urine volume (OR = 0.69; p = 4.07 × 10−4), excreted higher daily urinary sodium (OR = 0.71; p = 3.03 × 10−5), and/or were prescribed thyroxine (OR = 0.33; p = 1.20 × 10−2) had lower risk for iodine deficiency. Self-reported intake of dairy products was most strongly associated with iodine status (r = 0.24; p = 2.38 × 10−9) after excluding for iodine supplementation and T4 use. Participants residing in Quebec City (OR = 2.58; p = 1.74 × 10−4) and Vancouver (OR = 2.54; p = 3.57 × 10−4) were more susceptible to iodine deficiency than Hamilton or Ottawa. Also, greater exposure to abundant iodine uptake inhibitors from tobacco smoking and intake of specific goitrogenic foods corresponded to elevated urinary thiocyanate and nitrate, which were found for residents from Quebec City as compared to other clinical sites. Recent public health policies that advocate for salt restriction and lower dairy intake may inadvertently reduce iodine nutrition of Canadians, and further exacerbate regional variations in iodine deficiency risk.

Sources of Variation in Food-Related Metabolites during Pregnancy.

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.

Neighborhood Greenspace and Socioeconomic Risk are Associated with Diabetes Risk at the Sub-neighborhood Scale: Results from the Prospective Urban and Rural Epidemiology (PURE) Study.

Greenspace and socioeconomic status are known correlates of diabetes prevalence, but their combined effects at the sub-neighborhood scale are not yet known. This study derives, maps, and validates a combined socioeconomic/greenspace index of individual-level diabetes risk at the sub-neighborhood scale, without the need for clinical measurements. In two Canadian cities (Vancouver and Hamilton), we computed 4 greenspace variables from satellite imagery and extracted 11 socioeconomic variables from the Canadian census. We mapped 5125 participants from the Prospective Urban and Rural Epidemiology Study by their residential address and used age- and sex-dependent walking speeds to estimate individual exposure zones to local greenspace and socioeconomic characteristics, which were then entered into a principal component analysis to derive a novel diabetes risk index (DRI-GLUCoSE). We mapped index scores in both study areas and validated the index using fully adjusted logistic regression models to predict individual diabetes status. Model performance was then compared to other non-clinical diabetes risk indices from the literature. Diabetes prevalence among participants was 9.9%. The DRI-GLUCoSE index was a significant predictor of diabetes status, exhibiting a small non-significant attenuation with the inclusion of dietary and physical activity variables. The final models achieved a predictive accuracy of 75%, the highest among environmental risk models to date. Our combined index of local greenspace and socioeconomic factors demonstrates that the environmental component of diabetes risk is not sufficiently explained by diet and physical activity, and that increasing urban greenspace may be a suitable means of reducing the burden of diabetes at the community scale.

Serum metabolomic signatures of gestational diabetes in South Asian and white European women.

INTRODUCTION: This study aimed to identify serum metabolomic signatures associated with gestational diabetes mellitus (GDM), and to examine if ethnic-specific differences exist between South Asian and white European women. RESEARCH DESIGN AND METHODS: Prospective cohort study with a nested case-control analysis of 600 pregnant women from two Canadian birth cohorts; using an untargeted approach, 63 fasting serum metabolites were measured and analyzed using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariate logistic regression modeling was conducted overall and by cohort. RESULTS: The proportion of women with GDM was higher in South Asians (27.1%) compared with white Europeans (17.9%). Several amino acid, carbohydrate, and lipid pathways related to GDM were common to South Asian and white European women. Elevated circulating concentrations of glutamic acid, propionylcarnitine, tryptophan, arginine, 2-hydroxybutyric acid, 3-hydroxybutyric acid, and 3-methyl-2-oxovaleric acid were associated with higher odds of GDM, while higher glutamine, ornithine, oxoproline, cystine, glycine with lower odds of GDM. Per SD increase in glucose concentration, the odds of GDM increased (OR=2.07, 95% CI 1.58 to 2.71), similarly for metabolite ratios: glucose to glutamine (OR=2.15, 95% CI 1.65 to 2.80), glucose to creatinine (OR=1.79, 95% CI 1.39 to 2.32), and glutamic acid to glutamine (OR=1.46, 95% CI 1.16 to 1.83). South Asians had higher circulating ratios of glucose to glutamine, glucose to creatinine, arginine to ornithine, and citrulline to ornithine, compared with white Europeans. CONCLUSIONS: We identified a panel of serum metabolites implicated in GDM pathophysiology, consistent in South Asian and white European women. The metabolic alterations leading to larger ratios of glucose to glutamine, glucose to creatinine, arginine to ornithine, and citrulline to ornithine in South Asians likely reflect the greater burden of GDM among South Asians compared with white Europeans.

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.