The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 8: Knowledge Gaps and Status of Existing Research Programs in Canada.

Despite significant progress in medical research and public health efforts, gaps in knowledge of women's heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women.

En dépit des avancées importantes de la recherche médicale et des efforts en santé publique, il reste des lacunes dans les connaissances sur la santé cardiaque des femmes sur les plans de l'épidémiologie, du tableau clinique, de la prise en charge, des résultats, de l'éducation, de la recherche et des publications. Du point de vue historique, la cardiopathie a d'abord été perçue comme une maladie qui touchait les hommes et les individus de sexe masculin. De ce fait, la compréhension des risques particuliers et des symptômes qu'éprouvent les femmes est limitée. Ces lacunes dans les connaissances posent particulièrement problème puisqu'à l'échelle mondiale la cardiopathie est la cause principale de décès chez les femmes. Jusqu'à récemment, la recherche en cardiologie, notamment la recherche préclinique et clinique, ne portait pas sur le sexe et le genre. Le recrutement souvent limité aux participants masculins et aux individus dont l'identité de genre correspond au sexe masculin et l'absence d'analyses de données en fonction du sexe ou du genre ont eu pour conséquence un manque de données sur la façon dont les traitements et les interventions nuisent aux patientes féminines et aux individus dont l'identité de genre correspond au sexe féminin, et ce, de façon différente. Cette absence de données a mené à un traitement sous-optimal et à des limites de notre compréhension des mécanismes sous-jacents de la cardiopathie chez les femmes, et est directement reliée à nos connaissances limitées, et à nos lacunes en formation professionnelle et en éducation du public. Le fait que les femmes ne connaissent souvent pas leurs facteurs de risque de maladies du cœur ou les symptômes qu'elles peuvent éprouver entraîne des retards de diagnostic et de traitements. De plus, le fait que les prestataires de soins de santé ne reçoivent pas la formation adéquate pour poser le diagnostic et traiter la cardiopathie chez les femmes les mène à poser un mauvais diagnostic ou à ne pas traiter suffisamment. Pour pallier ces lacunes de connaissances, il faut une approche à plusieurs volets, qui porte notamment sur l'éducation et les changements dans les politiques, et qui repose sur la recherche fondée sur des données probantes. Dans ce chapitre, nous passons en revue l'état actuel de la recherche existante sur les maladies cardiovasculaires au Canada, plus particulièrement chez les femmes.

Women's Heart Health and the Menopausal Transition: Two Faces of the Same Coin.

The impact of the presence or absence of sex hormones on women's health is woefully underresearched. Fundamentally, women's bodies are now understood to spend considerable time under widely fluctuating hormonal influences, including puberty, pregnancy, peripartum, and menopause, and a woman's vessels are therefore preset for functional and physiological alterations based on levels of sex hormones. However, our understanding of the influences of sex hormones on the regulation of a multitude of biological and physiological processes has not translated into the development and/or collection or analyses of data on therapeutic treatments and/or outcomes in the context of women's disease management.

Les effets sur la santé des femmes associés à la présence ou à l'absence d'hormones sexuelles ont fait l'objet de trop peu d'études. On sait essentiellement que les taux d'hormones fluctuent considérablement tout au long des étapes de la vie des femmes, qu'il s'agisse de la puberté, de la grossesse, de la période périnatale et de la ménopause, et que leurs vaisseaux sont en fait préréglés pour permettre diverses modifications fonctionnelles et physiologiques en fonction du taux d'hormones sexuelles. Cependant, notre compréhension de l'influence des hormones sexuelles sur la régulation d'une multitude de processus biologiques et physiologiques ne s'est pas traduite par la collecte et/ou l'analyse de données sur les traitements ou les résultats thérapeutiques dans le contexte de la prise en charge de diverses maladies chez les femmes.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Myocardial Infarction Within 30 Days of Discharge From an Emergency Department: A Descriptive Study of Albertan Women.

Background: Cardiovascular diseases (CVDs) are the leading cause of premature death for Canadian women, which may be due partly to a lack of awareness of the presentation of acute coronary events in emergency departments (EDs). To address an identified gap in women's cardiovascular care, we sought to describe the clinical and comorbid factors of women who, following discharge from an ED, suffered a myocardial infarction (MI). Methods: Descriptive analyses were completed on a cohort of women who presented to an ED in Alberta, Canada, between January 1, 2010 and December 31, 2020, were discharged, and within 30 days of their index ED visit, were admitted to the hospital with an MI. The cohort was explored for clinical and comorbid data, ED visits pre-MI, type of MI, and presenting complaint/ primary diagnosis for the index ED visit. Results: 1380 women were included in this analysis with a mean age of 67 (standard deviation ±13) years. The frequencies of hypertension, diabetes, and dyslipidemia among the youngest women, aged 18-45 years, were 47.5%, 31.3%, and 48.8%, respectively. Women across all ages demonstrated a high prevalence of traditional CVD risk factors, and 22% of women presented to an ED 2 or more times within the 30 days pre-MI. Conclusions: Regardless of their age, the women in this cohort had notable CVD risk factors. Future research is required to better understand the phenomenon of women presenting multiple times to an ED pre-MI. Research is needed on life-stage-specific factors of women presenting to EDs pre-MI, to help reduce MI incidence.

Contexte: Les maladies cardiovasculaires représentent la principale cause de décès prématuré chez les Canadiennes, ce qui peut être en partie attribuable à un manque de connaissance des manifestations des événements coronariens aigus dans les services d'urgence. Pour combler une lacune observée dans les soins cardiovasculaires chez les femmes, nous avons tenté de décrire les facteurs cliniques et les facteurs de comorbidité chez les femmes qui, après avoir reçu leur congé du service d'urgence, ont subi un infarctus du myocarde (IM). Méthodologie: Des analyses descriptives ont été menées sur une cohorte de femmes qui se sont présentées dans un service d'urgence en Alberta, au Canada, entre le 1er janvier 2010 et le 31 décembre 2020, qui ont reçu leur congé et qui, dans les 30 jours suivant leur visite de référence aux urgences, ont été admises à l'hôpital pour un IM. L'analyse de la cohorte portait sur les données cliniques et les données de comorbidité, les consultations au service d'urgence avant l'IM, le type d'IM et la raison/le diagnostic primaire lors de la consultation de référence. Résultats: Cette analyse a porté sur 1380 femmes dont l'âge moyen était de 67 (écart-type ± 13) ans. Les fréquences d'hypertension, de diabète et de dyslipidémie chez les femmes les plus jeunes, âgées de 18 à 45 ans, étaient respectivement de 47,5 %, de 31,3 % et de 48,8 %. Les femmes de tous les âges présentaient une prévalence élevée de facteurs de risque classiques de maladies cardiovasculaires, et 22 % des femmes s'étaient présentées à un service d'urgence au moins 2 fois au cours des 30 jours ayant précédé l'IM. Conclusions: Indépendamment de l'âge, les femmes de cette cohorte présentaient des facteurs de risque de maladies cardiovasculaires notables. D'autres recherches s'imposent afin de mieux comprendre le phénomène des femmes qui se présentent plusieurs fois dans un service d'urgence dans la période précédant un IM. Une recherche doit être menée sur les facteurs spécifiques aux stades de la vie des femmes qui se présentent aux urgences avant un IM afin d'aider à réduire l'incidence des infarctus du myocarde.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 7: Sex, Gender, and the Social Determinants of Health.

Women vs men have major differences in terms of risk-factor profiles, social and environmental factors, clinical presentation, diagnosis, and treatment of cardiovascular disease. Women are more likely than men to experience health issues that are complex and multifactorial, often relating to disparities in access to care, risk-factor prevalence, sex-based biological differences, gender-related factors, and sociocultural factors. Furthermore, awareness of the intersectional nature and relationship of sociocultural determinants of health, including sex and gender factors, that influence access to care and health outcomes for women with cardiovascular disease remains elusive. This review summarizes literature that reports on under-recognized sex- and gender-related risk factors that intersect with psychosocial, economic, and cultural factors in the diagnosis, treatment, and outcomes of women's cardiovascular health.

Les profils de facteurs de risque, les facteurs sociaux et environnementaux, le tableau clinique, le diagnostic et le traitement des maladies cardiovasculaires montrent des différences importantes entre les femmes et les hommes. Il est plus probable que les femmes expérimentent des problèmes de santé complexes et multifactoriels, qui sont souvent en relation avec les disparités dans l'accès aux soins, la prévalence des facteurs de risque, les différences biologiques entre les sexes, les facteurs liés au genre et les facteurs socioculturels. De plus, la sensibilisation à la nature et à la relation intersectionnelles des déterminants socioculturels de santé, notamment les facteurs liés au sexe et au genre, qui influencent l'accès aux soins et les résultats cliniques des femmes atteintes d'une maladie cardiovasculaire demeure insaisissable. La présente revue résume la littérature qui porte sur les facteurs de risque liés au sexe et au genre peu reconnus qui se recoupent aux facteurs psychosociaux, économiques et culturels dans le diagnostic, le traitement et les résultats cliniques en lien avec la santé cardiovasculaire des femmes.

Impact of Secondary Amenorrhea on Cardiovascular Disease Risk in Physically Active Women: A Systematic Review and Meta-Analysis.

BACKGROUND: Exercise-associated secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's normal cardioprotective pathways. Estrogen may be essential in a woman's endothelial adaptations to exercise. The objective of this review was to assess the association between secondary amenorrhea in physically active women and cardiovascular disease (CVD) risk. METHODS AND RESULTS: A literature search was performed in January 2023 and updated in August 2023 of the Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Citation chaining was done to screen for additional studies. Eight sources were searched for gray literature. Studies that compared physically active women with amenorrhea to physically active women with eumenorrhea aged 18 to 35 years with evidence of CVD, alterations to cardiovascular physiology, or CVD risks were included. Eighteen observational studies from 3 countries were included. Overall, the quality of evidence was good. A meta-analysis was performed. Physically active women with secondary amenorrhea had significantly lower estradiol, flow-mediated dilation, resting heart rate, systolic blood pressure, and diastolic blood pressure and higher total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol. CONCLUSIONS: Estrogen deficiency resulting from exercise-associated secondary amenorrhea in physically active women may impact cardiovascular physiology and certain CVD risk factors. The research in this area is observational; therefore, findings should be interpreted cautiously. However, as exercise-associated secondary amenorrhea is reversible and the primary prevention of CVD is important for public health, it may be important to treat secondary amenorrhea and restore estrogen levels.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

INTRODUCTION: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. MATERIAL AND METHODS: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. RESULTS: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. CONCLUSIONS: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems.

Impact of secondary amenorrhea on cardiovascular disease risk in physically active women: a systematic review protocol.

OBJECTIVE: The objective of this review is to assess the association between secondary amenorrhea in physically active women and cardiovascular disease risk. INTRODUCTION: It is well established that a woman's risk of cardiovascular disease greatly increases after menopause. The sharp decline in estrogen is seen as a causal factor. Exercise-induced secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's cardioprotective pathways. Further, estrogen may be essential in a woman's endothelial adaptations to exercise. The impact of secondary amenorrhea on cardiovascular disease risk in premenopausal women is not well established. INCLUSION CRITERIA: This review will consider studies that include physically active women experiencing amenorrhea in any country. Only studies that present evidence of cardiovascular disease, alterations to cardiovascular physiology, or data on cardiovascular risk factors (eg, lipid profile changes) will be considered. The review will consider experimental or observational epidemiological study designs. METHODS: Searches will be conducted in CINAHL (EBSCOhost), the Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Two independent reviewers will screen titles, abstracts, and full texts, appraise methodological quality, and extract data from studies. Where possible, studies will be pooled in a statistical meta-analysis in addition to subgroup analyses. Where pooling is not possible, the findings will be presented in narrative format. Certainty of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. REVIEW REGISTRATION: PROSPERO CRD42023360781.

Impact of Sex and Gender on Metabolic Syndrome in Adults: A Retrospective Cohort Study From the Canadian Primary Care Sentinel Surveillance Network.

OBJECTIVE: Metabolic syndrome (MetS), a cluster of 5 interconnected factors, is the main contributor to cardiovascular disease. Although sex- and gender-related elements have been linked to MetS and its components, this association has not been explored among Canadians with or without MetS. In this study, we aimed to identify sex and gender differences in characteristics of MetS in the Canadian population. METHODS: This retrospective cohort study used data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database. The CPCSSN contains de-identified electronic health records of >1.5 million Canadians (2010-2019). Individuals 35 to 75 years of age who had a primary care encounter formed the study sample (N=37,813). Multiple logistic regression models were used to estimate adjusted odds ratios for sex and gender differences among Canadians with and without MetS, which was the primary outcome variable. RESULTS: The estimated prevalence of MetS was 41.9%. The risk of developing MetS was significantly lower among females compared with males (odds ratio 0.73, 95% confidence interval 0.70 to 0.76). However, the risk was higher in females who used antidepressants (odds ratio 1.53, 95% confidence interval 1.42 to 1.65). An equal distribution of deprivation indexes was observed between males and females with MetS, with risk slightly higher for those with material deprivation. Females were found to be the most socially deprived. CONCLUSIONS: This study provides important sex- and gender-specific differences in MetS among Canadians. Targeting sex- and gender-specific risk factors could assist in reversing the trend of adverse cardiovascular outcomes associated with MetS.

Role of sex and gender-related variables in development of metabolic syndrome: A prospective cohort study.

INTRODUCTION: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested. RESULTS: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Impact of Sex- and Gender-Related Factors on Length of Stay Following Non-ST-Segment-Elevation Myocardial Infarction: A Multicountry Analysis.

Background Gender-related factors are psycho-socio-cultural characteristics and are associated with adverse clinical outcomes in acute myocardial infarction, independent of sex. Whether sex- and gender-related factors contribute to the substantial heterogeneity in hospital length of stay (LOS) among patients with non-ST-segment-elevation myocardial infarction remains unknown. Methods and Results This observational cohort study combined and analyzed data from the GENESIS-PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome study), EVA (Endocrine Vascular Disease Approach study), and VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI [Acute Myocardial Infarction] Patients study) cohorts of adults hospitalized across Canada, the United States, Switzerland, Italy, Spain, and Australia for non-ST-segment-elevation myocardial infarction. In total, 5219 participants were assessed for eligibility. Sixty-three patients were excluded for missing LOS, and 2938 were excluded because of no non-ST-segment-elevation myocardial infarction diagnosis. In total, 2218 participants were analyzed (66% women; mean±SD age, 48.5±7.9 years; 67.8% in the United States). Individuals with longer LOS (51%) were more likely to be White race, were more likely to have diabetes, hypertension, and a lower income, and were less likely to be employed and have completed secondary education. No univariate association between sex and LOS was observed. In the adjusted multivariable model, age (0.62 d/10 y; P<0.001), unemployment (0.63 days; P=0.01), and some of countries included relative to Canada (Italy, 4.1 days; Spain, 1.7 days; and the United States, -1.0 days; all P<0.001) were independently associated with longer LOS. Medical history mediated the effect of employment on LOS. No interaction between sex and employment was observed. Longer LOS was associated with increased 12-month all-cause mortality. Conclusions Older age, unemployment, and country of hospitalization were independent predictors of LOS, regardless of sex. Individuals employed with non-ST-segment-elevation myocardial infarction were more likely to experience shorter LOS. Sociocultural factors represent a potential target for improvement in health care expenditure and resource allocation.

A comparison of synthetic data generation and federated analysis for enabling international evaluations of cardiovascular health.

Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.

Rural Prenatal Care by Nurse Practitioners: A Narrative Review.

Background: Rural Canadian populations face many challenges due to their geographical isolation, including inaccessible and inequitable primary health care. Specifically, pregnant women are at risk of not receiving prenatal care (PNC) due to physical and social barriers. Inadequate PNC can have detrimental effects on both maternal and neonatal health outcomes. Nurse practitioners (NPs) are an essential group of alternative primary care providers who can provide specialized care, including PNC, to these underserved populations. Objective: The purpose of this narrative review was to identify existing NP-led rural PNC programs in other health care systems to support maternal and neonatal outcomes. Methods: A systematic search was performed to identify articles published between 2002 and 2022 on CINAHL (EBSCO host) and MEDLINE (OVID). Literature was excluded if (1) the context was based in urban centers; (2) the study focused on specialized obstetrical/gynecological-based care; or (3) the study was published in a language other than English. The literature was assessed and synthesized into a narrative review. Results: The initial search identified 34 potentially relevant articles. Five broad themes were identified, including (1) barriers to care; (2) mobile health clinics; (3) collaborative or tiered models of care; (4) telemedicine; and (5) NPs as essential primary care providers. Conclusions: The introduction of a collaborative NP-led approach to rural Canadian settings has the potential to address barriers to PNC and provide efficient, equitable, and inclusive health care.

Psychosocial interventions and mental health in patients with cardiovascular diseases living in low- and middle-income countries: A systematic review and meta-analysis.

OBJECTIVE: Mental health issues are closely associated with symptoms and outcomes of cardiovascular diseases (CVDs). The magnitude of this problem is alarmingly high in low and middle-income countries (LMICs). This systematic review and meta-analysis aimed to examine the effectiveness of psychosocial interventions on mental health outcomes among patients with CVDs living in LMICs. METHODS: This review includes Randomized controlled trials (RCTs) and quasi-experimental studies conducted on adult patients who had a CVD and/or hypertension and located in LMICs. Studies published in English between 2010 and March, 2021 and which primarily reported mental health outcomes of resilience, self-efficacy, Quality of life (QoL), depression and anxiety were included. Studies were screened, extracted and critically appraised by two independent reviewers. Meta-analysis was conducted for RCTs and narrative summaries were conducted for all other studies. PRISMA guidelines were followed for reporting review methods and findings. RESULTS: 109 studies included in this review reported educational, nursing, behavioral and psychological, spiritual, relaxation, and mindfulness interventions provided by multidisciplinary teams. 14 studies reported self-efficacy, 70 reported QoL, 62 reported one or both of anxiety and depression, and no study was found that reported resilience as an outcome in this population. Pooled analysis showed improvements in self-efficacy and QoL outcomes. The majority of studies showed improvement in outcomes, though the quality of the included studies varied. CONCLUSION: Patients with CVDs in LMICs may experience improved mental health through the use of diverse psychosocial interventions. Evaluations are needed to investigate whether the impact of interventions on mental health are sustained over time.

Fundamental neurochemistry review: Old brain stories - Influence of age and sex on the neurodegeneration-associated lipid changes.

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age-associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age-related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non-biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age-related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid-related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid-lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid-reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach.

Age and Sex Determine Electrocardiogram Parameters in the Octodon degus.

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.

Magnesium in Kidney Function and Disease-Implications for Aging and Sex-A Narrative Review.

Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012-2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there's a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.