Impact of seasonal blood pressure changes on visit-to-visit blood pressure variability and related cardiovascular outcomes.

BACKGROUND: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk. METHODS: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model. RESULTS: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints. CONCLUSIONS: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations.

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.

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.

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.

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.

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.

Evaluation of Adiposity and Cognitive Function in Adults.

Importance: Excess adipose tissue increases other cardiovascular risk factors, which may be associated with vascular brain injury and cognitive impairment. However, the extent to which the amount and distribution of adipose tissue may be associated with lower cognitive scores, independent of its association with cardiovascular risk factors, is not well characterized. Objective: To investigate the association of adiposity on vascular brain injury and cognitive scores. Design, Setting, and Participants: A total of 9189 participants from the Canadian Alliance for Healthy Hearts and Minds (CAHHM) and the Prospective Urban Rural Epidemiological-Mind (PURE-MIND) cohort studies were included in this cross-sectional analysis. Of these adults, 9166 underwent bioelectrical impedance analysis to assess body fat (BF) percentage, and 6773 underwent magnetic resonance imaging to assess vascular brain injury and measure visceral adipose tissue (VAT) volume. Participants from CAHHM were recruited from January 1, 2014, to December 31, 2018, and PURE-MIND participants were recruited from January 1, 2010, to December 31, 2018. Both CAHHM and PURE-MIND comprise multisite, population-based cohorts. Participants from CAHHM are from Canada, and PURE-MIND participants are from Canada or Poland. Data analysis was performed from May 3 to November 24, 2021. Exposures: The percentage of BF and VAT were modeled as sex-specific quartiles. Vascular brain injury was defined as high white matter hyperintensities or silent brain infarction. Multivariable mixed models were used to examine factors associated with reduced cognitive scores. Main Outcomes and Measures: Cognitive function was assessed using the Digital Symbol Substitution Test (DSST; scores range from 0 to 133, with lower scores indicating lower cognitive function) and Montreal Cognitive Assessment (scores range from 0 to 30, with a score of ≥26 denoting normal cognitive function). Reduced cognition was defined as a DSST score less than 1 SD below the mean. Cardiovascular risk was assessed using the INTERHEART Risk Score (IHRS; scores range from 0 to 48; low risk is defined as a score of 0 to 9, moderate risk as 10 to 16, and high risk as 17 or higher). Results: A total of 9189 adults (mean [SD] age, 57.8 [8.8] years; 5179 [56.4%] women; and 1013 [11.0%] East and Southeast Asian; 295 [3.2%] South Asian; 7702 [83.8%] White European; and 179 [1.9%] other, including Black, Indigenous, mixed, and unknown ethnicity) participated in the study. Visceral adipose tissue was highly correlated with body adiposity measured by BF percentage (r = 0.76 in women; r = 0.70 in men). Cardiovascular risk factors increased with increasing BF percentage with the fourth quartile IHRS at 13.8 (95% CI, 13.5-14.0; P < .001 for trend) and with VAT with the fourth quartile IHRS at 13.3 (95% CI, 13.0-13.5; P < .001 for trend). Vascular brain injury increased with increasing BF percentage with the fourth quartile value at 8.6% (95% CI, 7.5%-9.8%; P = .007 for trend) and with increasing VAT with fourth quartile value at 7.2% (95% CI, 6.0-8.4; P = .05 for trend). Cognitive scores were lower with increasing BF percentage with the fourth quartile score of 70.9 (95% CI, 70.4-71.5; P < .001 for trend) and for VAT with the fourth quartile score of 72.8 (95% CI, 72.1-73.4; P < .001 for trend). For every 1-SD increase in BF percentage (9.2%) or VAT (36 mL), the DSST score was lower by 0.8 points (95% CI, 0.4-1.1; P < .001) for BF percentage and lower by 0.8 points (95% CI, 0.4-1.2; P < .001) for VAT, adjusted for cardiovascular risk factors and vascular brain injury. The population attributable risk for reduced DSST score for higher BF percentage was 20.5% (95% CI, 7.0%-33.2%) and for VAT was 19.6% (95% CI, 2.0%-36.0%). Higher BF percentage and VAT were not associated with Montreal Cognitive Assessment scores. Conclusions and Relevance: In this cross-sectional study, generalized and visceral adiposity were associated with reduced cognitive scores, after adjustment for cardiovascular risk factors, educational level, and vascular brain injury. These results suggest that strategies to prevent or reduce adiposity may preserve cognitive function.

Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk.

BACKGROUND: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed the association of self-reported physical activity with renal and CV outcomes in high-risk patients aged ≥ 55 years over a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program. METHODS: Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and χ2-test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed. RESULTS: Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of new albuminuria (p < 0.0001 for both) compared to lower exercise levels. Similar results were observed for those with and without diabetes without interaction for renal outcomes (p = 0.097-0.27). Physical activity was associated with reduced eGFR decline with a moderate association between activity and diabetes status (p = 0.05). CONCLUSIONS: Moderate physical activity was associated with improved kidney outcomes with a threshold at two sessions per week. The association of physical activity with renal outcomes did not meaningfully differ with or without diabetes but absolute benefit of activity was even greater in people with diabetes. Thus, risks were similar between those with diabetes undertaking high physical activity and those without diabetes but low physical activity. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov.uniqueidentifier :NCT00153101.

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).

Normal sex and age-specific parameters in a multi-ethnic population: a cardiovascular magnetic resonance study of the Canadian Alliance for Healthy Hearts and Minds cohort.

BACKGROUND: Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. METHODS AND RESULTS: Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). CONCLUSION: Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02220582. Registered 20 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582 .

Non-esterified fatty acids as biomarkers of diet and glucose homeostasis in pregnancy: The impact of fatty acid reporting methods: NEFA reporting methods affect dietary and cardiometabolic endpoints.

BACKGROUND: Sparse data exists on the utility of individual serum non-esterified fatty acids (NEFAs) as clinical and dietary biomarkers and how reporting methods could affect these associations. We investigated the associations of 19 serum NEFAs expressed as µM or mol%, with self-reported dietary intake data, and cardiometabolic health indicators in pregnant women. METHODS: In this cross-sectional study, 273 pregnant women in their second trimester each completed a semi-quantitative food-frequency questionnaire and provided fasting serum samples. Comprehensive serum NEFA analysis was performed by multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry. We evaluated the associations of NEFAs using two different reporting methods, with diet quality, specific foods intake, and measures of adiposity and glucose homeostasis. RESULTS: Consistently stronger dietary correlations were observed when expressed as mol%. Serum ω-3 NEFAs were associated with diet quality and fish/fish oil daily servings (DHA mol%, r= 0.37; p = 4.8e-10), and odd-chain NEFAs were associated with full-fat dairy intake (15:0 mol%, r = 0.23; p = 9.0e-5). Glucose intolerance was positively associated with odd chain NEFAs as expressed in µM (r = 0.21; p= 0.001) but inversely associated when expressed as mol% (r = -0.31; p= 2.2e-7). In contrast, monounsaturated NEFAs (µM and mol%) had robust positive associations with pre-pregnancy BMI, second trimester skin-fold thickness, glycated hemoglobin, fasting glucose, and glucose intolerance. CONCLUSIONS: This study demonstrates the utility of specific NEFAs and their sub-classes as viable dietary and clinical biomarkers when reported as their relative proportions. More research is needed to investigate inconsistencies between absolute concentrations and relative proportions when reporting fatty acids.

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.

Metabolite profiles and the risk of metabolic syndrome in early childhood: a case-control study.

BACKGROUND: Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen. METHODS: In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex. RESULTS: Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 [95% CI 1.25-1.93]) and glutamine/glutamate ratio (OR 0.82 [95% CI 0.67-1.00])) and the alanine-glucose cycle (alanine (OR 1.41 [95% CI 1.16-1.73])), amino acids metabolism (tyrosine (OR 1.33 [95% CI 1.10-1.63]), threonine (OR 1.24 [95% CI 1.02-1.51]), monomethylarginine (OR 1.33 [95% CI 1.09-1.64]) and lysine (OR 1.23 [95% CI 1.01-1.50])), tryptophan metabolism (tryptophan (OR 0.78 [95% CI 0.64-0.95])), and fatty acids metabolism (carnitine (OR 1.24 [95% CI 1.02-1.51])). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature. CONCLUSIONS: A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.

Cardiovascular outcomes in patients at high cardiovascular risk with previous myocardial infarction or stroke.

BACKGROUND: Guidelines recommend to start blood pressure (BP)-lowering drugs also according to cardiovascular risk including history of cardiovascular events. We hypothesized that in patients with a history of myocardial infarction (MI), stroke, both or none of those, the index events predict the next event and have different SBP risk associations to different cardiovascular outcomes. DESIGN AND MEASUREMENTS: In this pooled posthoc, nonprespecified analysis, we assessed outcome data from high-risk patients aged 55 years or older with a history of cardiovascular events or proven cardiovascular disease, randomized to the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease Trial investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months. Associations of mean achieved BP on treatment were investigated on MI, stroke and cardiovascular death. We identified patients with previous MI (N = 13 487), stroke (N = 4985), both (N = 1509) or none (N = 10 956) of these index events. Analyses were done by Cox regression, analysis of variance and Chi2-test. 30 937 patients with complete data were enrolled between 1 December 2001 and 31 July 2003, and followed until 31 July 2008. Data of both trials were pooled as the outcomes were similar. RESULTS: Patients with MI as index event had a higher risk to experience a second MI [hazard ratio 1.42 (confidence interval (CI) 1.20-1.69), P < 0.0001] compared with patients with no events but no increased risk for a stroke as a next event [hazard ratio 0.95 (CI 0.73-1.23), n.s.]. The risk was roughly doubled when they had both, MI and stroke before [hazard ratio 2.07 (CI 1.58-2.71), P < 0.0001]. Patients with a stroke history had a roughly three-fold higher likelihood to experience a second stroke [hazard ratio 2.89 (CI 2.37-3.53) P < 0.0001] but not MI [hazard ratio 1.07 (CI 0.88-1.32), n.s.]. Both types of index events increased roughly three-fold the risk of a second stroke compared with no previous events. The SBP-risk relationship was not meaningfully altered by the event history. After MI and stroke the risk for subsequent events and cardiovascular death was increased over the whole SBP spectrum. A J-shape relationship between BP and outcome was only observed for cardiovascular death. CONCLUSION: Previous MI and previous stroke are associated with increased risk for the same event in the future, independent of achieved SBP. Thus, secondary prevention may also be chosen according to the event history of patients. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov. Unique identifier: NCT00153101.