Sex and gender-based analysis and diversity metric reporting in acute care trials published in high-impact journals: a systematic review.

OBJECTIVE: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020. STUDY SELECTION: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome. DATA ABSTRACTION AND SYNTHESIS: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials. RESULTS: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005). CONCLUSIONS: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials. PROSPERO REGISTRATION NUMBER: CRD42022282565.

Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines.

Association of marital/partner status with hospital readmission among young adults with acute myocardial infarction.

INTRODUCTION: Despite evidence supporting the benefits of marriage on cardiovascular health, the impact of marital/partner status on the long-term readmission of young acute myocardial infarction (AMI) survivors is less clear. We examined the association between marital/partner status and 1-year all-cause readmission and explored sex differences among young AMI survivors. METHODS: Data were from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled young adults aged 18-55 years with AMI (2008-2012). The primary end point was all-cause readmission within 1 year of hospital discharge, obtained from medical records and patient interviews and adjudicated by a physician panel. We performed Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, clinical, and psychosocial factors. Sex-marital/partner status interaction was also tested. RESULTS: Of the 2,979 adults with AMI (2002 women [67.2%]; mean age 48 [interquartile range, 44-52] years), unpartnered individuals were more likely to experience all-cause readmissions compared with married/partnered individuals within the first year after hospital discharge (34.6% versus 27.2%, hazard ratio [HR] = 1.31; 95% confidence interval [CI], 1.15-1.49). The association attenuated but remained significant after adjustment for demographic and socioeconomic factors (adjusted HR, 1.16; 95% CI, 1.01-1.34), and it was not significant after further adjusting for clinical factors and psychosocial factors (adjusted HR, 1.10; 95%CI, 0.94-1.28). A sex-marital/partner status interaction was not significant (p = 0.69). Sensitivity analysis using data with multiple imputation and restricting outcomes to cardiac readmission yielded comparable results. CONCLUSIONS: In a cohort of young adults aged 18-55 years, unpartnered status was associated with 1.3-fold increased risk of all-cause readmission within 1 year of AMI discharge. Further adjustment for demographic, socioeconomic, clinical, and psychosocial factors attenuated the association, suggesting that these factors may explain disparities in readmission between married/partnered versus unpartnered young adults. Whereas young women experienced more readmission compared to similar-aged men, the association between marital/partner status and 1-year readmission did not vary by sex.

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.

Impact of Marital Stress on 1-Year Health Outcomes Among Young Adults With Acute Myocardial Infarction.

Background Stress experienced in a marriage or committed relationship may be associated with worse patient-reported outcomes after acute myocardial infarction (AMI), but little is known about this association in young adults (≤55 years) with AMI. Methods and Results We used data from VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), an observational cohort study that enrolled individuals aged 18 to 55 years with AMI (2008-2012). Marital stress was self-reported 1 month after AMI using the Stockholm Marital Stress Scale (categorized as absent/mild, moderate, and severe). Outcomes were physical/mental health (Short Form-12), generic health status (EuroQol-5 Dimensions), cardiac-specific quality of life and angina (Seattle Angina Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and all-cause readmission 1 year after AMI. Regression models were sequentially adjusted for baseline health, demographics (sex, age, race or ethnicity), and socioeconomic factors (education, income, employment, and insurance). Sex and marital stress interaction was also tested. Among 1593 married/partnered participants, 576 (36.2%) reported severe marital stress, which was more common in female than male participants (39.4% versus 30.4%, P=0.001). Severe marital stress was significantly associated with worse mental health (beta=-2.13, SE=0.75, P=0.004), generic health status (beta=-3.87, SE=1.46, P=0.008), cardiac-specific quality of life (beta=-6.41, SE=1.65, P<0.001), and greater odds of angina (odds ratio [OR], 1.49 [95% CI, 1.06-2.10], P=0.023) and all-cause readmissions (OR, 1.45 [95% CI, 1.04-2.00], P=0.006), after adjusting for baseline health, demographics, and socioeconomic factors. These associations were similar across sexes (P-interaction all >0.05). Conclusions The association between marital stress and worse 1-year health outcomes was statistically significant in young patients with AMI, suggesting a need for routine screening and the creation of interventions to support patients with stress recovering from an AMI.

Adherence to the Mediterranean Diet in Preventing Major Cardiovascular Events in Patients with Ischemic Heart Disease: The EVA Study.

BACKGROUND: Adherence to healthy dietary patterns, such as the Mediterranean diet (Med-diet), is recommended for the maintenance of cardiovascular health. The determinants for adherence to Med-diet and its importance in secondary cardiovascular disease prevention are still unclear. The aim of the study was to evaluate the influence of sex- and psycho-socio-cultural (i.e., gender-related) factors on Med-diet adherence and its role in preventing major cardiovascular events (MACEs) in patients with ischemic heart disease (IHD). METHODS: Med-diet adherence was evaluated among 503 consecutive adults with IHD. MACEs were collected during a long-term follow-up. RESULTS: Male Bem Sex-Role Inventory score (i.e., male personality traits) and physical functional capacity were associated with higher adherence, while cohabitation with a smoker and physical inactivity with poorer adherence. During a median follow-up of 22 months, 48 participants experienced MACEs (17.5%, 8.1%, and 3.9% of patients with low, medium, and high adherence, respectively; p = 0.016). At multivariate Cox--regression analysis, a greater adherence remained inversely associated with MACEs (HR: 0.49; 95% CI: 0.29-0.82; p = 0.006) after adjusting for confounding factors. CONCLUSION: The study suggests that gender-related factors have a role in maintaining a healthy dietary pattern. Improving Med-diet adherence may lower the risk of recurring cardiovascular events.

Association of Marital/Partner Status with Hospital Readmission Among Young Adults With Acute Myocardial Infarction.

Introduction: Despite evidence supporting the benefits of marriage on cardiovascular health, the impact of marital/partner status on the long-term readmission of young acute myocardial infarction (AMI) survivors is less clear. We aimed to examine the association between marital/partner status and 1-year all-cause readmission, and explore sex differences, among young AMI survivors. Methods: Data were from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled young adults aged 18-55 years with AMI (2008-2012). The primary end point was all-cause readmission within 1 year of hospital discharge, obtained from medical record, patient interviews, and adjudicated by a physician panel. We performed Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, clinical and psychosocial factors. Sex-marital/partner status interaction was also tested. Results: Of the 2,979 adults with AMI (2002 women [67.2%]; mean age 48 [interquartile range, 44-52] years), unpartnered individuals were more likely to experience all-cause readmissions compared with married/partnered individuals within the first year after hospital discharge (34.6% versus 27.2%, hazard ratio [HR]=1.31; 95% confidence interval [CI], 1.15-1.49). The association attenuated but remained significant after adjustment for demographic and socioeconomic factors (adjusted HR, 1.16; 95%CI, 1.01-1.34), and was not significant after further adjusting for clinical factors and psychosocial factors (adjusted HR, 1.10; 95%CI, 0.94-1.28). Sex-marital/partner status interaction was not significant (p=0.69). Sensitivity analysis using data with multiple imputation, and restricting outcomes to cardiac readmission yielded comparable results. Conclusions: In a cohort of young adults aged 18-55 years, unpartnered status was associated with 1.3-fold increased risk of all-cause readmission within 1 year of AMI discharge. Further adjustment for demographic, socioeconomic, clinical and psychosocial factors attenuated the association, suggesting that these factors may explain disparities in readmission between married/partnered versus unpartnered young adults. Whereas young women experienced more readmission compared to similar-aged men, the association between marital/partner status and 1-year readmission did not vary by sex.

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.

Young Women With Acute Myocardial Infarction: Risk Prediction Model for 1-Year Hospital Readmission.

Background: Although young women ( aged ≤ 55 years) are at higher risk than similarly aged men for hospital readmission within 1 year after an acute myocardial infarction (AMI), no risk prediction models have been developed for them. The present study developed and internally validated a risk prediction model of 1-year post-AMI hospital readmission among young women that considered demographic, clinical, and gender-related variables. Methods: We used data from the US Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study (n = 2007 women), a prospective observational study of young patients hospitalized with AMI. Bayesian model averaging was used for model selection and bootstrapping for internal validation. Model calibration and discrimination were respectively assessed with calibration plots and area under the curve. Results: Within 1-year post-AMI, 684 women (34.1%) were readmitted to the hospital at least once. The final model predictors included: any in-hospital complication, baseline perceived physical health, obstructive coronary artery disease, diabetes, history of congestive heart failure, low income ( < $30,000 US), depressive symptoms, length of hospital stay, and race (White vs Black). Of the 9 retained predictors, 3 were gender-related. The model was well calibrated and exhibited modest discrimination (area under the curve = 0.66). Conclusions: Our female-specific risk model was developed and internally validated in a cohort of young female patients hospitalized with AMI and can be used to predict risk of readmission. Whereas clinical factors were the strongest predictors, the model included several gender-related variables (ie, perceived physical health, depression, income level). However, discrimination was modest, indicating that other unmeasured factors contribute to variability in hospital readmission risk among younger women.

Contexte: Bien que les femmes jeunes (≤ 55 ans) présentent un risque plus élevé que les hommes du même âge de réadmission à l'hôpital dans l'année suivant un infarctus aigu du myocarde (IAM), il n'existe pas de modèle de prédiction des risques conçu spécialement pour elles. Dans le cadre de la présente étude, on a créé et validé à l'interne un modèle de prédiction des risques de réadmission à l'hôpital dans l'année suivant un IAM chez les femmes jeunes en tenant compte de variables démographiques, cliniques et associées au genre. Méthodologie: Nous avons utilisé les données de l'étude américaine VIRGO (variation du rétablissement : le rôle du genre dans les résultats des jeunes patientes ayant subi un IAM) (n = 2007 femmes), une étude observationnelle prospective menée auprès de jeunes patientes hospitalisées pour un IAM. Un modèle bayésien d'établissement de la moyenne a été utilisé pour la sélection du modèle et la méthode bootstrap a été utilisée pour la validation interne. L'étalonnage et la discrimination du modèle ont été évalués respectivement au moyen des courbes d'étalonnage et de la surface sous la courbe. Résultats: Dans l'année suivant l'IAM, 684 femmes (34,1 %) ont été réadmises à l'hôpital au moins une fois. Les facteurs prédictifs finaux du modèle sont notamment : toute complication survenue à l'hôpital, l'état de santé physique perçu au départ, la coronaropathie obstructive, le diabète, les antécédents d'insuffisance cardiaque congestive, le faible revenu (< 30 000 $ US), les symptômes dépressifs, la durée du séjour à l'hôpital et l'ethnie (blanc par rapport à noir). Parmi les neuf facteurs prédictifs retenus, trois sont associés au genre. Le modèle est bien étalonné et présente une discrimination modeste (surface sous la courbe = 0,66). Conclusions: Notre modèle de risque propre aux femmes a été conçu et validé à l'interne auprès d'une cohorte de femmes jeunes hospitalisées pour un IAM et peut être utilisé pour prédire le risque de réadmission. Bien que les facteurs cliniques soient les facteurs prédictifs les plus puissants, le modèle inclut plusieurs variables liées au genre (p. ex., état de santé physique perçu, dépression, revenu). Cependant, la discrimination étant modeste, d'autres facteurs non mesurés contribuent à la variabilité du risque de réadmission à l'hôpital chez les femmes plus jeunes.

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.

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease.

BACKGROUND: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. OBJECTIVES: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. METHODS: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. RESULTS: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1ß, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. CONCLUSIONS: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. CLINICAL TRIAL REGISTRATION: NCT02737982.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Association of Sociodemographic Characteristics With 1-Year Hospital Readmission Among Adults Aged 18 to 55 Years With Acute Myocardial Infarction.

Importance: Among younger adults, the association between Black race and postdischarge readmission after hospitalization for acute myocardial infarction (AMI) is insufficiently described. Objectives: To examine whether racial differences exist in all-cause 1-year hospital readmission among younger adults hospitalized for AMI and whether that difference retains significance after adjustment for cardiac factors and social determinants of health (SDOHs). Design, Setting, and Participants: The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study was an observational cohort study of younger adults (aged 18-55 years) hospitalized for AMI with a 2:1 female-to-male ratio across 103 US hospitals from January 1, 2008, to December 31, 2012. Data analysis was performed from August 1 to December 31, 2021. Main Outcomes and Measures: The primary outcome was all-cause readmission, defined as any hospital or observation stay greater than 24 hours within 1 year of discharge, identified through medical record abstraction and clinician adjudication. Logistic regression with sequential adjustment evaluated racial differences and potential moderation by sex and SDOHs. The Blinder-Oaxaca decomposition quantified how much of any racial difference was explained and not explained by covariates. Results: This study included 2822 participants (median [IQR] age, 48 [44-52] years; 1910 [67.7%] female; 2289 [81.1%] White and 533 [18.9%] Black; 868 [30.8%] readmitted). Black individuals had a higher rate of readmission than White individuals (210 [39.4%] vs 658 [28.8%], P < .001), particularly Black women (179 of 425 [42.1%]). After adjustment for sociodemographic characteristics, cardiac factors, and SDOHs, the odds of readmission were 34% higher among Black individuals (odds ratio [OR], 1.34; 95% CI, 1.06-1.68). The association between Black race and 1-year readmission was positively moderated by unemployment (OR, 1.68; 95% CI, 1.09- 2.59; P for interaction = .02) and fewer number of working hours per week (OR, 1.01; 95% CI, 1.00-1.02; P for interaction = .01) but not by sex. Decomposition indicates that 79% of the racial difference in risk of readmission went unexplained by the included covariates. Conclusions and Relevance: In this multicenter study of younger adults hospitalized for AMI, Black individuals were more often readmitted in the year following discharge than White individuals. Although interventions to address SDOHs and employment may help decrease racial differences in 1-year readmission, more study is needed on the 79% of the racial difference not explained by the included covariates.

Sex and gender aspects in diabetes mellitus: Focus on access to health care and cardiovascular outcomes.

Aims: The aim of this study was to elucidate whether sex and gender factors influence access to health care and/or are associated with cardiovascular (CV) outcomes of individuals with diabetes mellitus (DM) across different countries. Methods: Using data from the Canadian Community Health Survey (8.4% of respondent reporting DM) and the European Health Interview Survey (7.3% of respondents reporting DM), were analyzed. Self-reported sex and a composite measure of socio-cultural gender was constructed (range: 0-1; higher score represent participants who reported more characteristics traditionally ascribed to women). For the purposes of analyses the Gender Inequality Index (GII) was used as a country level measure of institutionalized gender. Results: Canadian females with DM were more likely to undergo HbA1c monitoring compared to males (OR = 1.26, 95% CI: 1.01-1.58), while conversely in the European cohort females with DM were less likely to have their blood sugar measured compared to males (OR = 0.88, 95% CI: 0.79-0.99). A higher gender score in both cohorts was associated with less frequent diabetes monitoring. Additionally, independent of sex, higher gender scores were associated with higher prevalence of self-reported heart disease, stroke, and hospitalization in all countries albeit European countries with medium-high GII, conferred a higher risk of all outcomes and hospitalization rates than low GII countries. Conclusion: Regardless of sex, individuals with DM who reported characteristics typically ascribed to women and those living in countries with greater gender inequity for women exhibited poorer diabetes care and greater risk of CV outcomes and hospitalizations.

The role of sex and gender in hypertension.

Hypertension (HTN) is a critical primary modifiable risk factor for the development of cardiovascular diseases, with recognized sex-based differences. While sex refers to one's biological genetic makeup and attributes, gender encompasses the individual's psycho-socio-cultural characteristics, including their environment and living conditions. The impact of each gendered variable may differ amongst men and women with respect to HTN. Applying a sex and gender-based lenses to inform our understanding of HTN has the potential to unveil important contributors of HTN-related cardiovascular outcomes. For instance, increased life stressors, work related anxiety and depression, typically have more pronounced effect on women than men with HTN. The impact of social surrounding including marital status and social support on HTN also differs amongst men and women. While married men are less likely to have higher blood pressure, single women, and those who never married are less likely to have HTN. Additionally, the beneficial role of social support is more pronounced in more historically marginalized cultural groups compared to majority. Finally, socioeconomic status, including education level and income have a linear and inverse relationship in blood pressure control in more resource-rich countries. The aim of this review is to summarize how sex and gender interact in shaping the clinical course of HTN demonstrating the importance of both sex and gender in HTN risk and its treatment. Hence, when investigating the role of gendered factors in HTN it is imperative to consider cultural, and social settings. In this narrative we found that employment and education play a significant role in manifestation and control of HTN particularly in women.