Search

Abstract Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P

Abstract Background Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth. Results Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin’s cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10–54) and South Asians (r = 0.66; p = 6.9 × 10–64). In both cohorts, Bohlin’s clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts. Conclusions These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin’s GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.

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.

Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging. Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials. Résumé: Contexte: Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n’est pas facile de réaliser des essais à répartition aléatoire dans un contexte pandémique. Méthodologie: Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d’inscription de 3 500 patients externes et de 2 500 patients hospitalisés présentant une COVID-19 symptomatique. L’essai mené auprès de patients externes visait à évaluer la colchicine par rapport aux soins habituels, et l’aspirine par rapport aux soins habituels. Le paramètre d’évaluation principal au terme de la répartition aléatoire des patients était l’hospitalisation ou le décès dans le groupe traité par la colchicine, et la thrombose majeure, l’hospitalisation ou le décès dans le groupe traité par l’aspirine. L’essai mené auprès de patients hospitalisés visant à évaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l’aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d’évaluation principal au terme de la répartition aléatoire des patients était le recours à l’oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l’oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par l’association rivaroxaban-aspirine. Résultats: À la fin de la période d’inscription, le 10 février 2022, 3 917 patients externes et 2 611 patients hospitalisés formaient la population des essais. Certains aspects se sont révélés problématiques, notamment le manque de données préliminaires sur les interventions à évaluer, les incertitudes liées aux taux d’événements prévus, les retards touchant les approbations réglementaires et éthiques et les interventions de recherche, de même que l’évolution de la pandémie de COVID-19. Conclusions: Les essais ACT détermineront l’efficacité du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l’aspirine, administrée seule ou en association avec le rivaroxaban, contre la COVID-19 légère, modérée ou sévère. Les leçons tirées de ces essais orienteront la planification d’essais ultérieurs.

Marie Loh, Weihua Zhang et al. use a genome-wide association study meta-analysis to examine variants associated with Type 2 diabetes (T2D) in South Asian and European ancestry cohorts. Their results provide further insights into the genetic mechanisms underlying T2D across ancestral populations.

Abstract Background Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance. Methods We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data. Results We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts. Conclusions Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants’ methylome.

Abstract 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

Abstract 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.

Background: Following severe limb ischemia requiring urgent/emergent revascularization, peripheral arterial disease patients suffer a high risk of recurrent atherothrombosis. Methods: Patients discharged from Hamilton General Hospital (Hamilton, Ontario) between April 2016 and September 2017 following severe limb ischemia requiring urgent/emergent revascularization were identified via the Local Health Integration Network CorHealth database, with supplemental information from chart review. Results: A total of 158 patients admitted for urgent/emergent revascularization were identified (148 alive at discharge). Among patients without a pre-existing indication for anticoagulation, 38.8% (n = 47) were discharged on single-antiplatelet therapy, 27.3% (n = 33) on dual-antiplatelet therapy, 19.8% (n = 24) on anticoagulants plus antiplatelet therapy, 6.6% (n = 8) on anticoagulants alone, and 2.6% (n = 3) on unknown therapy. Patients who received angioplasty with stenting were more likely be discharged on dual-antiplatelet therapy (hazard ratio [HR]: 7.14; 95% confidence interval [CI]: 2.87-17.76; P < 0.01); patients who received an embolectomy/thrombectomy were more likely be discharged on an anticoagulant alone (HR: 2.61; 95% CI: 1.00-6.81; P = 0.049); and patients who received peripheral bypass grafting were more likely be discharged on single-antiplatelet therapy (HR: 2.28; 95% CI: 1.11-4.69; P = 0.024). Neither statins (60.8% vs 56.3%; P = 0.23) nor renin–angiotensin–aldosterone system inhibitors (48.7% vs 50.6%; P = 0.58) were prescribed at higher rates at discharge, compared with the rate at admission. Conclusions: Substantial heterogeneity exists in antithrombotic prescription following urgent/emergent revascularization. No intensification of non-antithrombotic vascular protective medications occurred during hospitalization. Clinical trials and health system interventions to optimize medical therapy in peripheral arterial disease patients are urgently needed. Résumé: Introduction: Après une ischémie grave d’un membre ayant nécessité une revascularisation urgente/nouvelle revascularisation, les patients atteints d’une maladie artérielle périphérique ont un risque élevé de récidive d’athérothrombose. Méthodes: Nous avons recensé les patients qui ont obtenu leur sortie de la Hamilton General Hospital (Hamilton, Ontario) entre avril 2016 et septembre 2017 à la suite d’une ischémie grave d’un membre ayant nécessité une revascularisation urgente/nouvelle revascularisation via la base de données Local Health Integration Network CorHealth et grâce aux renseignements complémentaires issus de la revue des dossiers. Résultats: Nous avons recensé un total de 158 patients admis pour une revascularisation urgente/nouvelle revascularisation (148 patients en vie à la sortie de l’hôpital). Parmi les patients chez lesquels l’anticoagulation n’avait pas antérieurement été indiquée, 38,8 % (n = 47) avaient reçu à leur sortie de l’hôpital un simple traitement antiplaquettaire; 27,3 % (n = 33), une bithérapie antiplaquettaire; 19,8 % (n = 24), des anticoagulants plus un traitement antiplaquettaire; 6,6 % (n = 8), des anticoagulants seuls; 2,6 % (n = 3), un traitement inconnu. Les patients qui avaient subi une angioplastie et une pose d’endoprothèse étaient plus susceptibles d’obtenir à leur sortie de l’hôpital une bithérapie antiplaquettaire (rapport de risque [RR] : 7,14; intervalle de confiance [IC] à 95 % : 2,87-17,76; P < 0,01); les patients qui avaient subi une embolectomie, ou thrombectomie, étaient plus susceptibles d’obtenir à leur sortie de l’hôpital un anticoagulant seul (RR : 2,61; IC à 95 % : 1,00-6,81; P = 0,049); les patients qui avaient subi un pontage périphérique étaient plus susceptibles d’obtenir à leur congé de l’hôpital un simple traitement antiplaquettaire (RR : 2,28; IC à 95 % : 1,11-4,69; P = 0,024). Comparativement à l’admission, ni les statines (60,8 % vs 56,3 %; P = 0,23) ni les inhibiteurs du système rénine–angiotensine–aldostérone (48,7 % vs 50,6 %; P = 0,58) n’avaient été prescrits à des taux plus élevés à la sortie de l’hôpital. Conclusions: Nous observons une hétérogénéité substantielle de l’ordonnance des antithrombotiques après la revascularisation urgente/nouvelle revascularisation. L’hospitalisation n’a donné lieu à aucune augmentation des médicaments de protection vasculaire non antithrombotiques. Des essais cliniques et des interventions du système de santé qui permettent d’optimiser le traitement médical des patients atteints d’une maladie artérielle sont d’une urgente nécessité.

Abstract Background In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Methods Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Results Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. Conclusion The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex‐based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low‐dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74–1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00–1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P‐interaction=0.22), unplanned index limb revascularization (P‐interaction=0.64), and bleeding (P‐interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03–1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex‐based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216.

Background: A previous review of sex, gender, and equity within cardiovascular (CV) medicine, surgery, and science in Canada has revealed parity during medical and graduate school training. The purpose of this study was to explore sex and gendered experiences within the Canadian CV landscape, and their impact on career training and progression. Methods: An environmental scan was conducted of the Canadian CV landscape, which included an equity survey using Qualtrics software. Results: The environmental scan revealed that women remain underrepresented within CV training programs as trainees (12%–30%), program directors (33%), in leadership roles at the divisional level (21%), and in other professional or career-related activities (< 30%). Our analysis also showed improvements of career engagement at these levels of women at over time. The thematic analysis of the equity survey responses (n = 71 respondents; 83% female; 9.7% response rate among female Canadian Cardiovascular Society members) identified the following themes reported within the socio-ecological framework: desire to report inequities vs staying the course (individual level); desire for social support and mentorship and challenges of dual responsibilities (interpersonal level); concerns over exclusionary cliques and desire for respect and opportunity (organizational level); and increasing awareness and actions to overcome institutional barriers and accountability (societal level). Conclusions: Although women face challenges and remain underrepresented in CV medicine, surgery, and science, this study highlights potential opportunities for improving access of female medical, surgical, and research trainees and professionals to specialized cardiovascular training, career advancement, leadership, and research. Résumé: Contexte: Une étude antérieure portant sur le sexe, le genre et l'équité en médecine, chirurgie et sciences cardiovasculaires (CV) au Canada a révélé une parité au cours de la formation médicale et des études supérieures. L'objectif de cette étude était d’évaluer les expériences liées au sexe et au genre dans le paysage canadien du domaine CV, et leur impact sur la formation et la progression de carrière. Méthodes: Une analyse de l'environnement du paysage canadien dans le domaine CV a été réalisée, incluant une étude sur l'équité en utilisant le logiciel Qualtrics. Résultats: L'analyse de l'environnement a révélé que les femmes restent sous-représentées dans les programmes de formation du domaine CV que ce soit en tant que stagiaires (12 à 30 %), directrices de programme (33 %), dans les rôles de direction au niveau divisionnaire (21 %) et dans d'autres activités professionnelles ou associées à la carrière (< 30 %). Notre analyse a également montré une amélioration de l'engagement professionnel des femmes à ces niveaux au fil du temps. L'analyse thématique des réponses à l'enquête sur l'équité (n = 71 répondants; 83 % de femmes ; 9,7 % de taux de réponse parmi les membres féminins de la Société canadienne de cardiologie) a permis de dégager les thèmes suivants au sein du système socioécologique : désir de signaler les inégalités par rapport à la volonté de maintenir cap précis (au niveau individuel); désir de soutien social et de mentorat et défis liés à la double responsabilité (au niveau interpersonnel); préoccupations concernant les cliques exclusives et désir de respect et d’opportunité (au niveau organisationnel); et sensibilisation et actions accrues pour surmonter les obstacles institutionnels et les niveaux de responsabilité (au niveau sociétal). Conclusions: Bien que les femmes soient confrontées à des défis et restent sous-représentées dans les domaines de la médecine, de la chirurgie et des sciences CV, cette étude met en évidence les possibilités d'améliorer l'accès des stagiaires féminines et des professionnelles de la médecine, de la chirurgie et de la recherche à la formation spécialisée en cardiologie, à l'avancement de carrière, au rôle de direction et à la recherche.

Background: The intent of the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort is to understand the early determinants of subclinical cardiac and vascular disease and progression in adults selected from existing cohorts—the Canadian Partnership for Tomorrow’s Health, the Prospective Urban and Rural Evaluation (PURE) cohort, and the Montreal Heart Institute Biobank. We evaluated how well the CAHHM-Health Services Research (CAHHM-HSR) subcohort reflects the Canadian population. Methods: A cross-sectional design was used among a prospective cohort of community-dwelling adults aged 35-69 years who met the CAHHM inclusion criteria, and a cohort of adults aged 35-69 years who responded to the 2015 Canadian Community Health Survey-Rapid Response module. The INTERHEART risk score was calculated at the individual level with means and proportions reported at the overall and provincial level. Results: There are modest differences between CAHHM-HSR study participants and the 2015 Canadian Community Health Survey-Rapid Response respondents in age (56.3 vs 51.7 mean years), proportion of men (44.9% vs 49.3%), and mean INTERHEART risk score (9.7 vs 10.1). Larger differences were observed in postsecondary education (86.8% vs 70.2%), Chinese ethnicity (11.0% vs 3.3%), obesity (23.2% vs 29.3%), current smoker status (6.1% vs 18.4%), and having no cardiac testing (30.4% vs 55.9%). Conclusions: CAHHM-HSR participants are older, of higher socioeconomic status, and have a similar mean INTERHEART risk score, compared with participants in the Canadian Community Health Survey. Differing sampling strategies and missing data may explain some differences between the CAHHM-HSR cohort and Canadian community-dwelling adults and should be considered when using the CAHHM-HSR for scientific research. Résumé: Contexte: L’étude Alliance canadienne cœurs et cerveaux sains (CAHHM) vise à mieux comprendre les facteurs déterminants précoces et la progression de l’atteinte cardiovasculaire subclinique chez des adultes sélectionnés au sein de cohortes existantes – soit celles de l’étude menée par le Partenariat canadien pour la santé de demain, de l’étude PURE (Prospective Urban and Rural Evaluation) et de la biobanque de l’Institut de cardiologie de Montréal. Nous avons évalué la mesure dans laquelle la sous-cohorte du volet de recherche sur l’utilisation des services de santé de la CAHHM (CAHHM-HSR) représente la population canadienne. Méthodologie: Nous avons adopté une approche transversale pour étudier une cohorte prospective d’adultes vivant dans la communauté âgés de 35 à 69 ans et répondant aux critères d’inclusion de l’étude CAHHM, ainsi qu’une cohorte d’adultes âgés de 35 à 69 ans ayant participé au volet de réponse rapide de l’Enquête sur la santé dans les collectivités canadiennes (ESCC) de 2015. Le score de risque INTERHEART individuel des participants a été calculé à partir des moyennes et des proportions rapportées à l’échelle globale et à l’échelle provinciale. Résultats: Les différences entre les participants du volet CAHHM-HSR et ceux du volet de réponse rapide de l’ESCC de 2015 étaient minimes quant à l’âge (56,3 ans vs 51,7 ans en moyenne), à la proportion d’hommes (44,9 % vs 49,3 %) et au score de risque INTERHEART moyen (9,7 vs 10,1). On a toutefois noté des différences plus importantes en ce qui concerne les caractéristiques suivantes : éducation postsecondaire (86,8 % vs 70,2 %), origine ethnique chinoise (11,0 % vs 3,3 %), obésité (23,2 % vs 29,3 %), tabagisme actuel (6,1 % vs 18,4 %) et absence d’antécédents d’examen cardiaque (30,4 % vs 55,9 %). Conclusions: Les participants du volet CAHHM-HSR sont plus âgés et ont un statut socioéconomique plus élevé que ceux du volet de réponse rapide de l’ESCC, mais ont un score de risque INTERHEART moyen comparable. Les différences quant aux stratégies d’échantillonnage et des données manquantes pourraient expliquer certains des écarts observés entre la cohorte CAHHM-HSR et celle des adultes canadiens vivant dans la communauté; il conviendrait d’en tenir compte lorsqu’on utilise les données du volet CAHHM-HSR à des fins de recherche scientifique.

Nutritional studies rely on various biological specimens for FA determination, yet it is unclear how levels of serum NEFAs correlate with other circulating lipid pools. Here, we used a high-throughput method (

Abstract Background Perinatal health-seeking behaviours are influenced by various factors, including personal beliefs. South Asian women, who often live within a wide kinship system, can be influenced by the advice and guidance of their mothers and/or mothers-in-law. Methods To explore the cultural health perceptions of South Asian grandmothers within this context, we used constructivist grounded theory to sample and interview 17 South Asian grandmothers who reside in Southern Ontario, Canada. Interviews were audio-recorded, transcribed verbatim, and coded/analyzed by three independent coders. Results Many grandmothers emphasized that the preconception phase should focus on building healthy habits around nutrition, physical activity, and mental wellness; the pregnancy period should encompass an enriched environment (positive relationships, healthy routines, nutritional enhancement); and the postpartum phase should emphasize healing and restoration for both the mother and newborn (self-care, bonding, rebuilding healthy habits). Many of the grandmothers conceptualized these stages as a cyclical relationship where healing and restoration transitions gradually to re-establishing healthy habits before having a subsequent child. They also expressed responsibility in supporting their daughters and/or daughters-in-law with their family units and encouraging the transfer of perinatal health information. Conclusions South Asian grandmothers are involved in supporting the family units of their children and involving them in perinatal health programming can be an effective way to translate health knowledge to South Asian women. Video abstract. In order to impact a broad, diverse audience of community members, we collaborated with a South Asian film-maker to distil the research findings, write an impactful script, and produce a short digital story based on the research findings. Currently available on social media (https://www.youtube.com/watch?v=tjcNUVOwatU), the film was celebrated with a CIHR Institute for Human Development, Child and Youth Health Video Talks Prize in 2016.

Race, ethnicity, and ancestry are common classification variables used in health research. However, there has been no formal agreement on the definitions of these terms, resulting in misuse, confusion, and a lack of clarity surrounding these concepts for researchers and their readers. This article examines past and current understandings of race, ethnicity, and ancestry in research, identifies the distinctions between these terms, examines the reliability of these terms, and provides researchers with guidance on how to use these terms. Although race, ethnicity, and ancestry are often treated synonymously, they should be considered as distinct terms in the context of health research. Researchers should carefully consider which term is most appropriate for their study, define and use the terms consistently, and consider how their classification may be used in future research by others. The classification should be self-reported rather than assigned by an observer wherever possible.

Background The COMPASS trial demonstrated that in patients with peripheral arterial disease, the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on claudication distance. Study design Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from the baseline to 24 weeks, measured by 6 min walking test and treadmill test. The primary safety outcome is the incidence of major bleeding and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria. Summary The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.

Background: The global prevalence of hypertension in children and adolescents has increased over the past 2 decades and is the strongest predictor of adult hypertension. South Asians have an increased prevalence of metabolic syndrome associated risk factors including abdominal obesity, diabetes, and hypertension. All these factors contribute to their increased cardiovascular disease burden. Accurate and early identification of hypertension in South Asian children is a necessary aspect of cardiovascular disease prevention. Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard for pediatric blood pressure (BP) measurement. However, its utilization is limited due to the lack of validated normative reference data in diverse, multiethnic pediatric populations. Objective: The primary objective is to establish normative height-sex and age-sex-specific reference values for 24-h ABPM measurements among South Asian children and adolescents (aged 5-17 years) in Ontario and British Columbia, Canada. Secondary objectives are to evaluate differences in ABPM measurements by body mass index classification, to compare our normative data against pre-existing data from German and Hong Kong cohorts, and to evaluate relationships between habitual movement behaviors, diet quality, and ABPM measurements. Design: Cross-sectional study, quasi-representative sample. Setting: Participants will be recruited from schools, community centers, and places of worship in Southern Ontario (Greater Toronto and Hamilton area, including the Peel Region) and Greater Vancouver, British Columbia. Participants: We aim to recruit 2113 nonoverweight children (aged 5-17 years) for the primary objective. We aim to recruit an additional 633 overweight or obese children to address the secondary objectives. Measurements: Ambulatory BP monitoring measurements will be obtained using Spacelabs 90217 ABPM devices, which are validated for pediatric use. The ActiGraph GT3X-BT accelerometer, which has also been validated for pediatric use, will be used to obtain movement behavior data. Methods: Following recruitment, eligible children will be fitted with 24-h ABPM and physical activity monitors. Body anthropometrics and questionnaire data regarding medical and family history, medications, diet, physical activity, and substance use will be collected. Ambulatory BP monitoring data will be used to develop height-sex- and age-sex-specific normative reference values for South Asian children. Secondary objectives include evaluating differences in ABPM measures between normal weight, overweight and obese children; and comparing our South Asian ABPM data to existing German and Hong Kong data. We will also use compositional data analysis to evaluate associations between a child’s habitual movement behaviors and ABPM measures. Limitations: Bloodwork will not be performed to facilitate recruitment. A non-South Asian comparator cohort will not be included due to feasibility concerns. Using a convenience sampling approach introduces the potential for selection bias. Conclusions: Ambulatory BP monitoring is a valuable tool for the identification and follow-up of pediatric hypertension and overcomes many of the limitations of office-based BP measurement. The development of normative ABPM data specific to South Asian children will increase the accuracy of BP measurement and hypertension identification in this at-risk population, providing an additional strategy for primary prevention of cardiovascular disease.

To date, research on social capital in Indigenous contexts has been scarce. In this quantitative study, our objectives were to (1): Describe bonding social capital within four distinct First Nations communities in Canada, and (2) Explore the associations between bonding social capital and self-rated health in these communities. With community permission, cross-sectional data were drawn from the Canadian Alliance for Healthy Hearts and Minds study. Four reserve-based First Nations communities were included in the analysis, totaling 591 participants. Descriptive statistics were computed to examine levels of social capital among communities and logistic regression analyses were performed to identify social capital predictors of good self-rated health. Age, sex, education level, and community were controlled for in all models. Across the four communities in this study, areas of common social capital included frequent socialization among friends and large and interconnected family networks. Positive self-rated health was associated with civic engagement at federal or provincial levels (OR=1.65, p

Background: Achieving diversity, inclusion, and gender equity remains an elusive challenge for many institutions worldwide and is understudied in Canadian academic health science centres. Methods: McMaster University’s Department of Medicine undertook surveys and analyses to determine whether there was inequity in leadership positions and salaries, or unprofessional behaviour within the department. Measures of academic productivity in relation to gender for both educators and researchers were analyzed. The department began shifting policies to foster greater gender diversity and inclusion. A revision of the leadership selection process, incorporating tenets of equity and a new game theory–based strategy called Diversitive Agreement Versus Nash Equilibrium (DAvNE) was evaluated. Results: The department’s survey revealed underrepresentation of women and people of colour in leadership positions, with perceived barriers to their promotion. Both women and people of colour reported experiencing unprofessional behaviour directed toward them. A gender gap in base salary was observed, with female full professors being paid less. No difference in academic productivity was seen between male and female educators or researchers. The leadership competitions conducted under new selection processes emphasizing diversity resulted in 66% of participating women securing a leadership position, in comparison to 25% of participating men. People of colour made up 27% of members participating in these leadership competitions, but none was successful in obtaining a position. Conclusions: Diversity and inclusion disparities in the Department of Medicine at McMaster University indicate a need for further efforts and innovation to bring about greater gender and racial equity. Résumé: Contexte: La mise en place des conditions nécessaires à la diversité, à l’inclusion et à l’équité des genres demeure un défi difficile à relever pour de nombreux établissements dans le monde entier. C’est une démarche peu étudiée dans les centres universitaires canadiens des sciences de la santé. Méthodologie: Le département de médecine de l’Université McMaster a mené des sondages et des analyses en vue de déterminer s’il existait en son sein même des iniquités en matière d’attribution des postes de direction et de fixation des salaires, ou des comportements non professionnels. Des mesures de la productivité universitaire des éducateurs et des chercheurs ont été analysées en fonction des genres. Le département a entrepris une réforme de ses politiques afin de favoriser une plus grande diversité et inclusion des genres. Une révision du processus de sélection des candidats aux postes de direction, intégrant les principes d’équité et une nouvelle stratégie fondée sur la théorie des jeux appelée Diversitive Agreement Versus Nash Equilibrium (DAvNE [accord de diversité vs équilibre de Nash]), a été évaluée. Résultats: Le sondage du département a révélé qu’il existait une sous-représentation des femmes et des personnes de couleur parmi les titulaires des postes de direction, ainsi que des obstacles perçus à leur promotion. Tant les femmes que les personnes de couleur ont fait état de comportements non professionnels à leur endroit. Un écart entre les genres a été observé au chapitre de la rémunération de base, les professeurs titulaires de sexe féminin étant moins rémunérées. Aucune différence n’a été observée sur le plan de la productivité universitaire entre les femmes et les hommes au sein de l’effectif des éducateurs et des chercheurs. Les concours pour les postes de direction ont été organisés en fonction de nouveaux processus de sélection mettant l’accent sur la diversité. Au final, 66 % des candidats qui ont vu leur candidature retenue étaient des femmes et 25 %, des hommes. Dans le cadre de ces concours, 27 % des candidats étaient des personnes de couleur, mais aucun n’a réussi à obtenir un poste. Conclusions: Les disparités notées en matière de diversité et d’inclusion au sein du département de médecine de l’Université McMaster montrent que l’atteinte d’une plus grande équité des genres et des races passe par des efforts et une innovation soutenus.

Given the significant health burden of childhood obesity, it is imperative that effective programs be better understood. When evaluating obesity prevention efforts, one must recognize the contextual factors which drive the disproportionate risk of obesity between populations. This systematic review sought to understand if programs aimed at obesity prevention and/or the promotion of healthy lifestyle behaviours for Indigenous children are effective.We conducted a search using Medline, EMBASE, PsychINFO, ERIC, CINAHL and iPORTAL databases from inception to August 13, 2019. We included experimental and quasi-experimental studies. The main outcomes of interest were change in anthropometrics, nutrition or physical activity. Our narrative synthesis included an assessment of study quality using the Effective Public Health Practice Project Quality assessment tool.A total of 34 studies met selection criteria. Most studies used a quasi-experimental design (n = 25) and were assessed as low to moderate quality (n = 32). Three studies showed a significant change in anthropometric measures, 14 studies demonstrated at least one significant nutrition-related behaviour or dietary-pattern change, and six studies demonstrated a significant impact on physical activity.This systematic review of programs to prevent obesity among Indigenous children finds a limited impact on anthropometric measurements. Future studies must prioritize Indigenous knowledge and ways of knowing to lead all phases of development, implementation, and evaluation of programs.

Abstract Cardiovascular diseases including coronary heart disease, stroke, and peripheral arterial disease were responsible for an estimated 18 million deaths in 2017. Despite advances in management over the past several decades, these patients continue to have substantial risk of subsequent cardiovascular events. We provide a narrative review of randomized clinical trials evaluating direct oral anticoagulants (DOACs) for the treatment of acute coronary syndromes, noncardioembolic ischemic stroke, embolic stroke of undetermined source, and peripheral arterial disease. In these conditions, considerations for use of single antiplatelet therapy, dual antiplatelet therapy, or low‐dose DOACs used together with antiplatelet therapy are presented.

Background: Guyana experiences health challenges related to both communicable and non-communicable diseases. Cardiovascular disease (CVD) is the most common non-communicable disease in Guyana. The main causes of the increased prevalence of non-communicable diseases are modifiable risk factors (e.g. obesity, hypertension, elevated cholesterol, unhealthy dietary patterns) and non-modifiable risk factors (e.g. age and genetics). Objective: The aim of this review is to understand CVD and risk factor data, in the context of ethnicity in Guyana. Methods: A review of the published literature as well as government and international health agency reports was conducted. All publications from 2002–2018 describing CVD and related risk factors in Guyana were screened and extracted. Findings: The population of Guyana is comprised of six ethnic groups, of which East Indian (39.8%) and African (29.3%) are the majority. CVD accounts for 526 deaths per 100,000 individuals per year. Among Indo-Guyanese and Afro-Guyanese, CVD is the primary cause of death affecting 32.6% and 22.7% of the populations, respectively. Within the Indo-Guyanese and Afro-Guyanese communities there is a high prevalence of hypertension and diabetes among individuals over the age of 50. There is a lack of available data describing ethnic disparities in CVD and related risk factors such as obesity, smoking, alcohol, physical activity and diet in Guyana. Conclusions: Important knowledge gaps remain in understanding the ethnic disparities of CVD and related risk factors in Guyana. Future research should focus on high risk populations and implement widespread screening and treatment strategies of common risk factors such as hypertension, diabetes, and elevated cholesterol to curb the epidemic of CVD in Guyana.

Abstract We assessed the association between depression status and prevalent and incident type 2 diabetes (T2D) as well as the interaction between depression and a genetic risk score (GS) based on 20 T2D single-nucleotide polymorphisms (SNPs) in a multi-ethnic longitudinal study. We studied 17,375 participants at risk for dysglycemia. All participants had genotypic and phenotypic data collected at baseline and 9,930 participants were followed-up for a median of 3.3 years. Normal glucose tolerance (NGT), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and T2D statuses were determined using an oral glucose tolerance test and the 2003 American Diabetes Association criteria. Depression was diagnosed at baseline using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV). Multivariate logistic regression models were adjusted for age, sex, ethnicity and body-mass index and an interaction term GS X depression was added to the model. After appropriate Bonferroni correction, no significant association between depression and T2D-related traits (IFG/IGT, T2D and dysglycemia), and no significant interaction between the GS and depression status was observed at baseline or follow-up. Our longitudinal data do not support an association between depression and abnormal glycemic status. Moreover, depression does not modify the effect of T2D predisposing gene variants.

Abstract The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array. Genotype scores (GS) were calculated for TC, HDL-C, LDL-C and TG. Linear and mixed-effects regressions adjusted for sex, age and population stratification were performed. The GS was associated with LDL-C level at 3 and 5 years (β = 0.017 ± 0.003, P = 2.9 × 10−8; β = 0.020 ± 0.003, P = 5.7 × 10−9) and from birth to 5 years (β = 0.013 ± 0.003, P = 2.6 × 10−7). The GS was associated with TC level at 3 and 5 years (β = 0.009 ± 0.002, P = 9.1 × 10−7; β = 0.009 ± 0.002, P = 7.7 × 10−6). CETP rs3764261 was associated with the HDL-C level from birth to 5 years (β = 0.064 ± 0.014, P = 7.4 × 10−6). AMPD3 rs2923084 was associated with the HDL-C level at 5 years (β = 0.096 ± 0.024, P = 9.7 × 10−5). Known loci associated with blood lipids in adults are associated with TC, LDL-C and HDL-C, but not TG in early life. Genetically predisposed children may benefit from early lipid lowering preventative strategies.

Abstract Background The infant gut is rapidly colonized by microorganisms soon after birth, and the composition of the microbiota is dynamic in the first year of life. Although a stable microbiome may not be established until 1 to 3 years after birth, the infant gut microbiota appears to be an important predictor of health outcomes in later life. Methods We obtained stool at one year of age from 173 white Caucasian and 182 South Asian infants from two Canadian birth cohorts to gain insight into how maternal and early infancy exposures influence the development of the gut microbiota. We investigated whether the infant gut microbiota differed by ethnicity (referring to groups of people who have certain racial, cultural, religious, or other traits in common) and by breastfeeding status, while accounting for variations in maternal and infant exposures (such as maternal antibiotic use, gestational diabetes, vegetarianism, infant milk diet, time of introduction of solid food, infant birth weight, and weight gain in the first year). Results We demonstrate that ethnicity and infant feeding practices independently influence the infant gut microbiome at 1 year, and that ethnic differences can be mapped to alpha diversity as well as a higher abundance of lactic acid bacteria in South Asians and a higher abundance of genera within the order Clostridiales in white Caucasians. Conclusions The infant gut microbiome is influenced by ethnicity and breastfeeding in the first year of life. Ethnic differences in the gut microbiome may reflect maternal/infant dietary differences and whether these differences are associated with future cardiometabolic outcomes can only be determined after prospective follow-up.

Abstract Background The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes. Methods/Design Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition. Discussion CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

This article describes the methods taken to create an understanding of the perinatal health beliefs of elder Indigenous women of the Six Nations of the Grand River in Ontario, Canada. Our study paired constructivist grounded theory data collection and analysis methods with an Indigenous epistemological framework. We aimed to create knowledge that was specific to an Indigenous context, which was useful and resonant with both Indigenous and Western readers. The multidisciplinary research team included Indigenous and non-Indigenous members and worked with a common appreciation for multiple knowledge sources. We offer an account of our process and methodological principles to serve as an illustrative case study of bringing together diverse approaches when working with Indigenous communities.

Recent genome-wide association studies (GWAS) have reproducibly identified loci associated with plasma triglycerides (TG), HDL cholesterol, and LDL cholesterol. We sought to replicate these findings in a multiethnic population-based cohort using the curated single nucleotide polymorphism (SNP) set found on the new Illumina cardiovascular disease (CVD) beadchip, which contains approximately 50,000 SNPs densely mapping approximately 2,100 genes, selected based on their potential role in CVD. The sample consisted of individuals with European (n = 272), South Asian (n = 330), and Chinese (n = 304) ancestry. Identity by state clustering successfully classified individuals according to self-reported ethnicities. Associations between TG and APOA5, TG and LPL, HDL and CETP, and LDL and APOE were all identified (P < 2 × 10−6). In 13 loci, associations with the same SNP or a proxy SNP were identified in the same direction as previously reported (P < 0.05). Assessing the cumulative number of risk-associated alleles at multiple replicated SNPs increased the proportion of explained lipoprotein variance over and above traditional variables such as age, sex, body mass index, and ethnicity. The findings indicate the potential utility of the Illumina CVD beadchip, but they underscore the need to consider meta-analysis of results from commonly studied clinical or epidemiological samples.