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Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

Background An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. Methods A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. Results We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). Conclusions In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.

Women with a history of preeclampsia (PE) have increased risk of cardiovascular disease (CVD) later in life. However, the molecular determinants underlying this risk remain unclear. We sought to understand how circulating miRNA levels are affected by prior PE, and related to biological pathways underpinning cardiovascular disease. RNA sequencing was used to profile plasma levels of 2578 miRNAs in a retrospective study of women with a history of PE or normotensive pregnancy, in two independent cohorts with either acute coronary syndrome (ACS) (n = 17–18/group) or no ACS (n = 20/group). Differential miRNA alterations were assessed in relation to a history of PE (within each cohort) or ACS (across cohorts), and compared with miRNAs previously reported to be altered during PE. A history of PE was associated with altered levels of 30 and 20 miRNAs in the ACS and non-ACS cohorts, respectively, whereas ACS exposure was associated with alterations in 259 miRNAs. MiR-206 was identified at the intersection of all comparisons relating to past/current PE and ACS exposure, and has previously been implicated in atherogenic activities related to hepatocytes, vascular smooth muscle cells and macrophages. Integration of all differentially altered miRNAs with their predicted and experimentally validated targets in silico revealed a number of highly targeted genes with potential atherogenic functions (including NFAT5, CCND2 and SMAD2), and one significantly enriched KEGG biological pathway (Wnt signaling) that was shared between all exposure groups. The present study provides novel insights into miRNAs, target genes and biological pathways that may underlie the long-term cardiovascular sequelae of PE.

Background The extent to which race influences in‐hospital quality of care for young adults (≤55 years) with acute myocardial infarction (AMI) is largely unknown. We examined racial disparities in in‐hospital quality of AMI care and their impact on 1‐year cardiac readmission. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolling young Black and White US adults with AMI (2008–2012). An in‐hospital quality of care score (QCS) was computed (standard AMI quality indicators divided by the total a patient is eligible for). Multivariable logistic regression was performed to identify factors associated with the lowest QCS tertile, including interactions between race and social determinants of health. Among 2846 young adults with AMI (median 48 years [interquartile range 44–52], 67.4% women, 18.8% Black race), Black individuals, especially women, exhibited a higher prevalence of cardiac risk factors and social determinants of health and were more likely to experience a non–ST‐segment–elevation myocardial infarction than White individuals. Black individuals were more likely in the lowest QCS tertile than White individuals (40.8% versus 34.7%; P =0.003). The association between Black race and low QCS (odds ratio [OR], 1.25; 95% CI, 1.02–1.54) was attenuated by adjustment for confounders. Employment was independently associated with better QCS, especially among Black participants (OR, 0.76; 95% CI, 0.62–0.92; P‐ interaction =0.02). Black individuals experienced a higher rate of 1‐year cardiac readmission (29.9% versus 20.0%; P Conclusions Black individuals with AMI received lower in‐hospital quality of care and exhibited a higher rate of cardiac readmissions than White individuals. Black individuals had a lower quality of care if unemployed, highlighting the intersection of race and social determinants of health.

Background Readmission over the first year following hospitalization for acute myocardial infarction (AMI) is common among younger adults (≤55 years). Our aim was to develop/validate a risk prediction model that considered a broad range of factors for readmission within 1 year. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young adults aged 18 to 55 years hospitalized with AMI across 103 US hospitals (N=2979). The primary outcome was ≥1 all‐cause readmissions within 1 year of hospital discharge. Bayesian model averaging was used to select the risk model. The mean age of participants was 47.1 years, 67.4% were women, and 23.2% were Black. Within 1 year of discharge for AMI, 905 (30.4%) of participants were readmitted and were more likely to be female, Black, and nonmarried. The final risk model consisted of 10 predictors: depressive symptoms (odds ratio [OR], 1.03; 95% CI, 1.01–1.05), better physical health (OR, 0.98; 95% CI, 0.97–0.99), in‐hospital complication of heart failure (OR, 1.44; 95% CI, 0.99–2.08), chronic obstructive pulmomary disease (OR, 1.29; 95% CI, 0.96–1.74), diabetes mellitus (OR, 1.23; 95% CI, 1.00–1.52), female sex (OR, 1.31; 95% CI, 1.05–1.65), low income (OR, 1.13; 95% CI, 0.89–1.42), prior AMI (OR, 1.47; 95% CI, 1.15–1.87), in‐hospital length of stay (OR, 1.13; 95% CI, 1.04–1.23), and being employed (OR, 0.88; 95% CI, 0.69–1.12). The model had excellent calibration and modest discrimination (C statistic=0.67 in development/validation cohorts). Conclusions Women and those with a prior AMI, increased depressive symptoms, longer inpatient length of stay and diabetes may be more likely to be readmitted. Notably, several predictors of readmission were psychosocial characteristics rather than markers of AMI severity. This finding may inform the development of interventions to reduce readmissions in young patients with AMI.

Background: Women with physical disabilities are faced with challenges in many aspects of life-education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. Methods: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. Results: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers’ attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. Conclusions: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants’ experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women. Contexte: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l’éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. Méthodologie: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l’échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d’une approche phénoménologique herméneutique inspirée par Ricœur. Résultats: Deux grands thèmes ressortent de l’analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu’elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d’attente, les services de transport coûteux et peu fiables, les problèmes d’accessibilité et les obstacles liés à l’attitude des fournisseurs de soins vis-à-vis de l’incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d’avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L’autoprise en charge d’une incapacité physique et d’une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l’autonomie sociale. Conclusions: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l’équité et l’inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d’améliorer les résultats chez ces femmes. Funding was received from the Women’s Xchange 15K Challenge, Women’s College Hospital, Toronto, Ontario, Canada.

Influenza immunization protects seniors against influenza and its potentially serious complications. It is uncertain whether standard-dose (SD) quadrivalent vaccine offers better protection over other formulations in the elderly. In this study, we compared the effectiveness of SD-trivalent, high-dose (HD) trivalent, SD-quadrivalent, and adjuvanted trivalent vaccines in seniors (≥65 years) in a real-world setting. We selected over 200,000 individuals in each of 6 influenza seasons from 2012 to 2018 using MarketScan® databases. The two outcomes were hospitalization or emergency room (ER) visit due to (1) influenza or (2) pneumonia. Here, SD-quadrivalent was associated with higher risk of influenza-related hospitalization/ER visit (adjusted hazard ratio (aHR) 1.14 and 95% confidence interval (95% CI) 1.05–1.24) and of pneumonia-related hospitalization/ER visit (aHR 1.04 and 95% CI 1.01–1.07) vs. HD-trivalent. SD-trivalent followed similar trends compared to HD-trivalent (aHR 1.16 and 95% CI 1.06–1.27 for hospitalized/ER visit influenza; aHR 1.07 and 95% CI 1.05–1.10 for hospitalized/ER visit pneumonia). We could not demonstrate risk differences between SD vaccine formulations and between adjuvanted trivalent and one of the other three vaccines. Risk estimates slightly varied across seasons. These findings suggest that SD vaccine formulations vs. HD-trivalent were associated with higher risk of hospitalization/ER visit for influenza and pneumonia in seniors.

The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).

Background Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known. Methods We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM). Results We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups. Conclusion Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM.

Objective To assess the feasibility and acceptability of using a Sequential Multiple Assignment Randomized Trial (SMART) to optimize the delivery of a web-based, stress management intervention for patients with a cardiovascular disease (CVD). Methods 59 patients with a CVD and moderate stress were randomized to a self-directed web-based stress management program (n = 30) or the same intervention plus lay telephone coaching (n = 29). After 6 weeks, non-responders were re-randomized to continue with their initial intervention or switched to motivational interviewing (MI). Feasibility, acceptability, and clinical significance were assessed. Results SMART procedures were feasible. Attrition rates were almost twice as high in the web-only group than the lay coach group. This might be because of the low satisfaction (47%) in the web-only group. On average, 1.7/5 modules were completed. Effect sizes for stress and quality of life generally exceeded 0.2 (clinical benchmark), except for the group that initially received lay coaching and then switched to MI. Conclusions Results suggest that a larger trial would be feasible. Issues pertaining to attrition and satisfaction for non-responders need to be addressed. Practice implications Findings contribute to the evidence on how best to develop and deliver e-Health interventions to maximize their efficacy while remaining cost-effective.

Background The prevalence of non-communicable diseases (NCDs) is rising in low and middle-income countries (LMIC). We aimed to report on the prevalence of NCDs in pregnancy and their associated perinatal outcomes in a regional hospital in Haiti. Methods We conducted the “Diabète et hYpertension Artéerielle et leurs issues MAternelles et Néonatales” (DYAMAN) prospective cohort study in a regional hospital in Haiti. Pregnant women presenting to care at 24-28 weeks were screened and treated for diabetes (DM) and hypertensive disorders of pregnancy (HDP) using setting-adapted protocols. Prevalence of NCDs and associated maternal-neonatal outcomes were described. Results 715 women were included, of which 51 (7.1%) had DM, 90 (12.6%) had HDP, and 30 (4.2%) had both DM and HDP (DM/HDP). Of 422 (59%) women delivered in hospital, 58 (13.7%) had preeclampsia, including 5 (8.6%) with eclampsia. Preterm birth

Background: Stroke is one of the most common cerebrovascular diseases causing permanent disability, and decreased quality of life (QoL). Both sex and gender have been reported to be associated with health outcomes. Gender, unlike biological sex, encompasses the psycho-socio-cultural roles, behaviors and identities of men, women, and gender-diverse people. Hypothesis: To examine the association between sociocultural gender, biological sex and health status among stroke survivors in the Canadian population. Methods: Data from cycles 2013-2014 and 2015-16 (n=237,121) of the Canadian Community Health Survey (CCHS) were analyzed. The primary endpoint of the study was Health Utility Index (HUI), a measure of health status and QoL. This index measures a range of health domains (i.e. vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain) and ranges between -0.36 (severe health state) to 1 (perfect health state). A gender score was computed based on the Genesis-Praxy method, using a principal component analysis-derived propensity score method. The final gender scores ranging from 0 to 1 (higher score identifying characteristics traditionally ascribed to women) included household size, perceived life stress, education, sense of belonging to community, marital status, and income. All statistical analyses were performed using R (V.4.0.2) with survey design. Results: Amongst 3,773 (1.1%) stroke survivors in two cycles, 47.8% were female and a majority were older than 50 years (85.3%). Overall, 76.4% of the stroke survivors had moderate to severe HUI ( Conclusion: Characteristics traditionally ascribed to women’s gender and female sex were associated with poorer health status in stroke survivors. Gender-related factors must be targeted for improving the health status of patients suffering from stroke.

Preeclampsia is a common hypertensive disorder in pregnant women and whose causes and consequences have focused primarily on cardiovascular outcomes on the mother and offspring, often without taking into consideration the possible effects on the brain. One possible cause of preeclampsia has been attributed to alterations in the renin-angiotensin system, which has also been linked to cognitive decline. In this pilot study, we use a transgenic mouse model that chronically overexpresses human angiotensinogen and renin (R+A+ mice) that displayed characteristics of preeclampsia such as proteinuria during gestation. Offspring of these mothers as well as from control mothers were also examined. We were primarily interested in detecting whether cognitive deficits were present in the mothers and offspring in the long term and used a spatial learning and memory task as well as an object recognition task at three timepoints: 3, 8, and 12 months post-partum or post-natal, while measuring blood pressure and performing urine analysis after each timepoint. While we did not find significant deficits in preeclamptic mothers at the later timepoints, we did observe negative consequences in the pups of R+A+ mice that coincided with hemodynamic alterations whereby pups had higher whisker-evoked oxygenated hemoglobin levels and increased cerebral blood flow responses compared to control pups. Our study provides validation of this preeclampsia mouse model for future studies to decipher the underlying mechanisms of long-term cognitive deficits found in offspring.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. There is robust evidence of heterogeneity in underlying mechanism, manifestation, prognosis, and response to treatment of CVD between male and female patients. Gender, which refers to the socially constructed roles, behaviours, expressions, and identities of individuals, is an important determinant of CV health, and its consideration might help in attaining a broader understanding of the observed sex differences in CVD. Established risk factors such as hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking are well known to contribute to CVD. However, despite the differences in CVD risk between male and female, most studies looking into the magnitude of effect of each risk factor have traditionally focused on male subjects. While biological sex influences disease pathophysiology, the psycho-socio-cultural construct of gender can further interact with this effect. Behavioural, psychosocial, personal, cultural, and societal factors can create, repress, or strengthen underlying biological CV health differences. Although mechanisms of action are largely unclear, it is suggested that gender-related factors can further exacerbate the detrimental effect of established risk factors of CVD. In this narrative review, we explore the current literature investigating the role of gender in CV risk and its impact on established risk factors as a fundamental step toward precision medicine.

Background Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations. Methods The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women). Results Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: β = −1.33, 95% confidence interval [CI] −1.44 to −1.22; AT-HIS: β = −1.08, 95% CI −1.26 to −0.89)) were associated with worse CVH, female sex (CCHS: β = 0.35, 95% CI (0.33-0.37); AT-HIS: β = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians. Conclusions These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country.

Introduction: Although readmission over the first year following hospitalization for acute myocardial infarction (AMI) is common among younger adults (18-55 yrs), there is no available risk prediction model for this age group. Existing risk models have been developed in older populations, have modest predictive ability, and exhibit methodological drawbacks. We developed a risk prediction model that considered a broad range of demographic, clinical, and psychosocial factors for readmission within 1-year of hospitalization for AMI among young adults. Methods: Young AMI adults (18-55 yrs) were enrolled from the prospective observational VIRGO study (2008-2012) of 3,572 patients. Data were obtained from medical record abstraction, interviews, and adjudicated hospitalization records. The outcome was all-cause readmission within 1-year. We used a two-stage selection process (LASSO followed by Bayesian Model Averaging) to develop a risk model. Results: The median age was 48 years (IQR: 44,52), 67.1% were women, and 20.1% were Non-white or Hispanic. Within 1-year, 906 patients (25.3%) were readmitted. Patients who were readmitted were more likely to be female, black, and had a clustering of adverse risk factors and co-morbidities. From 61 original variables considered, the final multivariable model of readmission within 1-year of discharge consisted of 14 predictors (Figure) . The model was well calibrated (Hosmer-Lemeshow P >0.05) with moderate discrimination (C statistic over 33 imputations: 0.69 development cohort). Conclusion: Adverse clinical risk factors such as diabetes, hypertension and prior AMI, but also female sex, access to specialist care, and major depression were associated with a higher risk of readmission at 1-year post AMI. This information is important to inform the development of interventions to reduce readmissions in young patients with AMI.

Introduction: The extent to which race influences in-hospital quality of care among young adults with acute myocardial infarction (AMI) is unknown. We examined racial differences in in-hospital quality of AMI care in young adults and described the patient and/or clinical characteristics associated with potential disparities in care. Methods: Data from the GENESIS-PRAXY (Canada) and the VIRGO (U.S.) prospective cohorts of young adults with AMI were analyzed. Among a total of 4,048 adults with AMI (≤55 years) (median=49 years [IQR 44-52], 22% non-white, 58% women), we calculated an in-hospital quality of care score (QCS) for AMI (quality indicators divided by total, with higher scores indicating better care) based on AHA quality of care standards, reporting data disaggregated by race. We categorized race as white versus non-white, which included Black, Asian and North American Indigenous populations. Results: This cohort was comprised of 906 non-white individuals and 3142 white individuals. Non-white adults exhibited a clustering of adverse cardiac risk factors, psychosocial risk factors and comorbidities versus whites; they had higher rates of hypertension, diabetes, alcohol abuse and prior AMI and lower rates of physical activity. They were more likely to have a low SES and receive low social support, and were less likely to be employed, a primary earner, or married/living with a partner. Non-white individuals were also more likely to experience a NSTEMI and less likely to receive cardiac rehabilitation, smoking cessation counseling as well as dual antiplatelet therapy at discharge. Furthermore, non-white individuals had a lower crude QCS than whites (QCS=69.99 vs 73.29, P-value Conclusion: Non-white individuals with AMI exhibited higher rates of adverse psychosocial and clinical characteristics than white individuals yet non-white race was independently associated with lower in-hospital quality of care. Interventions are needed to improve quality of AMI care in non-white young adults.

The ‘real-world’ patient population of metastatic melanoma is not fully represented in clinical trials investigating checkpoint inhibitors. We described therapy discontinuation in an unselected population-based cohort of adults with metastatic melanoma who started therapy with pembrolizumab, nivolumab, or nivolumab/ipilimumab from January 2015 to August 2017. Therapy discontinuation was defined as a gap between doses beyond 120 days, and/or initiation of another cancer therapy. We estimated drug-specific rate ratios for therapy discontinuation adjusted for age, sex, comorbidities, health care use, and past cancer therapies. We included 876 metastatic melanoma patients initiating pembrolizumab (44.3%), nivolumab/ipilimumab (31.2%), and nivolumab (24.5%). At 12 months of follow-up, the probabilities of therapy discontinuation were 49.9% (95% confidence interval, CI 43.6–56.5) for pembrolizumab, 58.8% (95% CI 50.5–67.3) for nivolumab, and 59.2% (95% CI 51.7–66.8) for nivolumab/ipilimumab. Stratified analyses based on prior cancer therapy, brain metastases at baseline, and sex showed similar trends. In multivariable analyses, compared with pembrolizumab, patients starting nivolumab (rate ratio 1.38, 95% CI 1.08–1.77) or nivolumab/ipilimumab (rate ratio 1.30, 95% CI 1.02–1.65) were more likely to discontinue therapy. Our findings indicate frequent discontinuations of checkpoint inhibitors at one year. The lower discontinuation associated with pembrolizumab should be confirmed in further studies.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.

Postmenopausal women are more likely to have uncontrolled hypertension and are at higher risk of cardiovascular disease compared with age-matched men. Blood pressure variability is emerging as a predictor of adverse cardiovascular outcomes and may be implicated in the relationship between menopause and worsened vascular health in women. We conducted an observational study, BRAVE (Blood pRessure And Vascular hEalth around menopause) to study this relationship.Normotensive perimenopausal women were recruited. Blood pressure variability was measured through 24-h blood pressure monitoring. Vascular health was assessed through arterial stiffness (carotid-femoral pulse wave velocity), carotid intima-media thickness and endothelial function (reactive hyperemic index). Multivariate models were performed to identify factors associated with blood pressure variability and arterial stiffness in perimenopausal women.Forty-nine healthy women (mean age 52.9 ± 4.0, 63% postmenopausal) were recruited. There was a high prevalence (40%) of night non-dipping, a measure of an abnormal pattern of blood pressure variability. Aside from night dipping, other measures of blood pressure variability were similar between premenopausal and postmenopausal women. In the multivariate analysis, body mass index was the only factor associated independently with different measures of blood pressure variability, including the maximum overnight blood pressure (ß = 1.95, p 0.01). The latter was also significantly associated with arterial stiffness (ß = 0.035, p = 0.048). Finally, poor sleep was independently associated with an increase in arterial stiffness.Abnormal blood pressure variability, particularly night non-dipping, is common in normotensive perimenopausal women. Maximum overnight blood pressure is independently associated with arterial stiffness and may identify women at higher cardiovascular risk.

Background: The quality of care among young adults with acute myocardial infarction (AMI) may be related to biological (sex) or psycho-socio-cultural (gender) determinants or healthcare system-level factors. Objectives: To examine whether sex, gender, and the type of healthcare system influence the quality of AMI care among young adults. Methods: A total of 4,564 AMI young adults ( Results: Women in the multipayer system had the highest risk factor burden. Across the phases of care for AMI, 20% of quality indicators were missed in both sexes. High stress, earner status, and social support were associated with a higher QCS in the pre-AMI phase, whereas only employment and earner status were associated with QCS in all other phases. In the pre-AMI phase, women had higher QCS than men, mainly in the single-payer system (adjusted-OR=1.85, 95%CI 1.46,2.35 vs. 1.07, 95%CI 0.84,1.36, P-interaction=0.002). Regardless of sex, only employment status had a greater effect in the multipayer system (adjusted-OR=0.59, 95%CI 0.44,0.78 vs 1.13, 95%CI 0.89,1.44, P-interaction0.05). Finally, in the post-AMI phase, men and women had a lower QCS, predominantly in the multipayer system. However, primary earners had higher QCS regardless of the healthcare system. Conclusion: Sex, gender, and the healthcare system affected the quality of care after AMI. Women had a poorer in-hospital than men and young adults had suboptimal post-discharge care. Being unemployed lowered the quality of care, more so in the multipayer healthcare system.

Aims Randomized trials suggest reductions in all-cause mortality and heart failure (HF) rehospitalizations with catheter ablation (CA) in patients with atrial fibrillation (AF) and HF. Whether these results can be replicated in a real-world population with long-term follow-up or varies over time is unknown. We sought to evaluate the long-term effectiveness of CA in reducing the incidence of all-cause mortality, HF hospitalizations, stroke, and major bleeding in AF–HF patients. Methods and results In a cohort of patients newly diagnosed with AF–HF in Quebec, Canada (2000–2017), CA patients were matched 1:2 to controls on time and frequency of hospitalizations. Confounders were controlled for using inverse probability of treatment weighting. Multivariable Cox models adjusted for the presence of cardiac electronic implantable devices and medication use during follow-up, and the effect of time since CA was modelled with B-splines. For non-fatal outcomes, the Lunn–McNeil approach was used to account for the competing risk of death. Among 101 933 AF–HF patients, 451 underwent CA and were matched to 899 controls. Over a median follow-up of 3.8 years, CA was associated with a statistically significant reduction in all-cause mortality [hazard ratio 0.4 (95% confidence interval 0.2–0.7)], but no difference in stroke or major bleeding. The hazard of HF rehospitalization for CA patients, relative to non-CA patients, varied with time since CA (P = 0.01), with a reduction in HF rehospitalizations until approximately 3 years post-CA. Conclusion Compared with matched non-CA patients, CA was associated with a long-term reduction in all-cause mortality and a reduction in HF rehospitalizations until 3 years post-CA.

Background Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.

Background: The reasons behind low adherence to the Mediterranean diet (Med-diet) are still not entirely known. We aimed to evaluate the effect of biological (i.e., sex-related) and psycho-socio-cultural (i.e., gender-related) factors on Med-diet adherence. Methods: Baseline Med-diet adherence was measured using a self-administered questionnaire among adults with ischemic heart disease (IHD) from the EVA (Endocrine Vascular Disease Approach) study. A multivariable analysis was performed to estimate the effect of sex- and gender-related factors (i.e., identity, roles, relations, and institutionalized gender) on low adherence. Results: Among 366 participants (66 ± 11 years, 31% women), 81 (22%) adults with low adherence demonstrated higher rates of diabetes, no smoking habit, lower male BSRI (Bem Sex Role Inventory) (median (IQR) 4.8 (4.1 to 5.5) vs. 5.1 (4.5 to 5.6) and p = 0.048), and higher Perceived Stress Scale 10 items (PSS-10) (median (IQR) 19 (11 to 23) vs. 15 (11 to 20) and p = 0.07) scores than those with medium-high adherence. In the multivariable analysis, only active smoking (odds ratio, OR = 2.10, 95% confidence interval, CI 1.14 to 3.85 and p = 0.017), PPS-10 (OR = 1.04, 95% CI 1.00 to 1.08, and p = 0.038) and male BSRI scores (OR = 0.70, 95% CI 0.52 to 0.95, and p = 0.021) were independently associated with low adherence. Conclusions: Male personality traits and perceived stress (i.e., gender identity) were associated with low Med-diet adherence regardless of the sex, age, and comorbidities. Therefore, gender-sensitive interventions should be explored to improve adherence in IHD.

Preeclampsia increases a woman’s risk of stroke and leads to short-term cognitive complaints. Our objective was to assess the impact of preeclampsia on long-term cognitive performance. This is a retrospective cohort study using data from the Coronary Artery Risk Development in Young Adults cohort of healthy individuals (18–30 years) recruited from the general population in 3 cities in the United States, followed for 25 years (1985–2010). Psychomotor speed (Digit Symbol Substitution Test), executive function (Stroop Test), and memory (Rey Auditory Verbal Learning Test) were contrasted between women with and without preeclampsia using multivariate linear regression. We included 568 parous women (193 with preeclampsia and 375 with normotensive pregnancy) without baseline neurological disease or depression matched according to delivery period. Approximately 18 years after delivery, preeclamptic women scored significantly lower on Digit Symbol Substitution Test than women with normotensive pregnancy (73.21±14.79 versus 75.87±15.22; P =0.047) and on the third trial of Stroop Test (correct answers: 38.85±3.62 versus 39.42±1.87; P =0.014; completion time: 44.02±10.48 versus 41.62±10.61 seconds; P =0.01), but there were no differences in Rey Auditory Verbal Learning Test. These differences were attenuated after adjustment for age, body mass index, hypertension, education, and depression. Similar differences in neurocognitive scores were noted between women with other hypertensive disorders of pregnancy and normotensive pregnancy. Hypertension in pregnancy does not seem to be independently associated with neurocognitive impairment later in life.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.

Background Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). Objectives To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. Methods A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. Results From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). Conclusion No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

Key Points Question Among young adults with acute myocardial infarction (AMI) in the US and Canada, is quality of care associated with sex, social determinants of health (SDOH), and health care systems? Findings In this cohort study of 4048 adults 55 years or younger with AMI, being treated in the US (multipayer system) relative to Canada (single-payer system) was associated with a lower in-hospital and post-AMI quality-of-care score, regardless of all SDOH factors except unemployment. Lower in-hospital quality of care was associated with 1-year readmission rates in the US only. Meaning These findings suggest that health care systems and unemployment are associated with quality of AMI care., This cohort study of young adults aged 55 years or younger with acute myocardial infarction (AMI) in the US and Canada examines whether quality of care for AMI is associated with sex, social determinants of health, and health care systems., Importance Quality of care of young adults with acute myocardial infarction (AMI) may depend on health care systems in addition to individual-level factors such as biological sex and social determinants of health (SDOH). Objective To examine whether the quality of in-hospital and postacute care among young adults with AMI differs between the US and Canada and whether female sex and adverse SDOH are associated with a low quality of care. Design, Setting, and Participants This retrospective cohort analysis used data from 2 large cohorts of young adults (aged ≤55 years) receiving in-hospital and outpatient care for AMI at 127 centers in the US and Canada. Data were collected from August 21, 2008, to April 30, 2013, and analyzed from July 12, 2019, to March 10, 2021. Exposures Sex, SDOH, and health care system. Main Outcomes and Measures Opportunity-based quality-of-care score (QCS), determined by dividing the total number of quality indicators of care received by the total number for which the patient was eligible, with low quality of care defined as the lowest tertile of the QCS. Results A total of 4048 adults with AMI (2345 women [57.9%]; median age, 49 [interquartile range, 44-52] years; 3004 [74.2%] in the US) were included in the analysis. Of 3416 patients with in-hospital QCS available, 1061 (31.1%) received a low QCS, including more women compared with men (725 of 2007 [36.1%] vs 336 of 1409 [23.8%]; P

BACKGROUND The impact of biological sex and social determinants of health (gender) on the prevalence of cardiovascular (CV) risk factors such as diabetes mellitus (DM) may vary by culture and health systems. In this study, we aimed to elucidate how sex and gender influence access to care and CV outcomes of individuals with DM across different countries. METHODS AND RESULTS Data from the Canadian Community Health Survey (2015-16) (N=109,659, 53.7% Females, 8.4% DM) and the European Health Interview Survey (N=316,333, 51.3% Females, 7.3% DM), were analyzed. A composite measure of socio-cultural gender was constructed (score range: 0-1; higher score identifying characteristics traditionally ascribed to women). The relationship between the gender score, antihyperglycemic care, complications and hospitalization of individuals with DM was assessed with a logistic regression model. European countries were stratified based on their Gender Inequality Index (GII); which quantifies gender disparity and inequity amongst various countries in the world, from low-GII (GII =0.1635). Characteristics traditionally ascribe to women (i.e., higher gender score) included greater stress level, being widowed or divorced, larger household size, higher education, good sense of belonging to community, and lower income in Canadians; while being divorced or widowed, having greater household size, lower education and lower income were found in Europeans. Sex and gender significantly influenced the standard care of patients with diabetes including periodic glucose and HbA1C monitoring. Canadian diabetic females were more likely to check their HbA1c (OR: 1.29, 95%CI:1.03-1.6), while European counterparts were less likely to check their blood sugar (OR: 0.89, 95%CI:0.79-0.99). A higher gender score in both populations was associated with less frequent monitoring of HbA1C and blood glucose levels (Table 1). When stratifying by GII, DM patients in countries with medium and high GII were less likely to check their blood glucose levels compared to low GII countries (Table1). Additionally, higher gender scores independent of sex were associated with higher risk of heart disease, stroke and hospitalization in all countries albeit European countries with medium to high GII, conferred a higher risk of all complications and hospitalization rates (Table1). CONCLUSION Regardless of biological sex, diabetic individuals with characteristics typically ascribed to women and those living in countries with greater gender inequality, exhibited poorer antihyperglycemic care, greater risk of cardiovascular complications, and higher hospitalization rates. Country-specific gender related factors and gender disparity must be targeted for improving health status and access to care of patients with DM.

Background Glucocorticoid excess has been linked with cardiovascular disease. Little is known about the long-term cortisol response in patients after acute coronary syndrome. Design The objective of this study was to describe the distribution of salivary cortisol in the post-acute phase of acute coronary syndrome and to describe the association of late-night salivary cortisol with cardiovascular risk factors. Methods We used late-night salivary cortisol measurements post-discharge to estimate hypothalamic-pituitary-adrenal axis activity in 309 patients aged 18–55 years enrolled in the GENESIS-PRAXY study from January 2009–April 2013. We evaluated hypothalamic-pituitary-adrenal axis activity and its association with hypertension, dyslipidemia, diabetes, smoking, family history, prior acute coronary syndrome, psychiatric diseases, acute coronary syndrome severity, as well as mortality and rate of rehospitalization at 12 months. Results Persistently elevated late-night salivary cortisol>2.92 nmol/l was seen in 99 (32.0%) patients: within the range of what may be seen in Cushing’s disease. Elevated late-night salivary cortisol was associated with previous acute coronary syndrome (13.3% vs 24.2%, p = 0.02), peripheral vascular disease (3.8% vs 13.1%, p = 0.002), and smoking (32.9% vs 46.5% p = 0.02). Elevated late-night salivary cortisol was associated with higher hemoglobin A1c values (5.6 ± 3.0 vs 6.1 ± 2.9, p = 0.008) and lower high density lipoprotein values (0.94 ± 0.53 vs 0.86 ± 0.50, p = 0.01). There were no differences in psychiatric symptom scores, acute coronary syndrome severity or mortality, and rate of rehospitalization at 12 months. Conclusions Many patients post-acute coronary syndrome have prolonged, marked activation of the hypothalamic-pituitary-adrenal axis. Late-night salivary cortisol co-associates with several cardiovascular risk factors. Further studies are needed to confirm the exact role of hypothalamic-pituitary-adrenal axis activity in the pathophysiology of cardiovascular disease.

BACKGROUND Little is known about whether there are differences in medication use between older patients of Chinese descent, those of South Asian descent and other Canadian patients after acute ischemic or primary intracerebral hemorrhagic stroke. The aim of this population-based study was to evaluate potential ethnic differences in secondary prevention pharmacotherapy after acute stroke. METHODS Using health administrative data, we conducted a retrospective analysis of all patients aged 66 years or more admitted to hospital with acute stroke in Ontario (1997-2011) and British Columbia (1997-2009). We compared prescriptions filled for statins, warfarin, any antihypertensive agent, the recommended combination of angiotensin-converting-enzyme (ACE) inhibitor and diuretic, and the combination of ACE inhibitor, diuretic and statin within 1 year after ischemic or primary intracerebral hemorrhagic stroke. RESULTS There were 118 362 patients with acute stroke (3430 Chinese, 2075 South Asian and 112 857 other Canadians). Among those with ischemic stroke (n = 108 699), Chinese patients were less likely than other Canadian patients to fill prescriptions for the combination of ACE inhibitor, diuretic and statin (adjusted odds ratio [OR] 0.64 [95% confidence interval (CI) 0.55-0.74]) and, in those with atrial fibrillation, for warfarin (adjusted OR 0.75 [95% CI 0.59-0.95]). There were no differences in filling of prescriptions for antihypertensive therapy overall between the 3 groups. Among patients with intracerebral hemorrhagic stroke (n = 9663), Chinese patients were less likely than other Canadian patients to fill prescriptions for the combination of ACE inhibitor and diuretic (adjusted OR 0.51 [95% CI 0.38-0.69]), and South Asians were more likely than other Canadian patients to fill prescriptions for any antihypertensive agent (adjusted OR 1.73 [95% CI 1.21-2.49]). INTERPRETATION We identified ethnic differences in filling of prescriptions for several secondary prevention medications after acute stroke. The reasons underlying these differences need to be investigated.

While it has been identified that gender (socially manufactured roles, behaviors, expressions, and identities) plays a central role in men's and women's health, the distinction between gender and sex (biological attributes) has largely been ignored in health science research. The purpose of this study was to look at the unique contributions of sex, age, and the Gender Index (GI) to baseline health status in a cohort of patients with coronary artery disease (CAD).Questions that comprised the GI were included in the follow-up questionnaire sent to patients in the APPROACH registry. To examine the relationship between sex, gender, and health status, a sequential linear regression modeling approach was used.A total of 632 patients completed the GI between July and August 2015. The women were significantly older (68 years vs. 66 years, p = 0.02) and significantly more likely to have hypertension (50.8% vs. 38.8%, p = 0.02) compared to the men. Women reported significantly lower mean Seattle Angina Questionnaire (SAQ) scores compared to men. The inclusion of age into the models did not change the relationship between sex and the SAQ scales. However, the inclusion of the GI attenuated the relationship between sex and the SAQ scale scores.Our results support the concept that sex differences in health status outcomes may be better explained by patient's gender-related characteristics, than biological sex characteristics. More importantly, the GI offers a pragmatic composite score to assess the effects of psychosocial factors that researchers interested in measuring gender could use in studies of subjects with CAD.

Background: Current guidelines are relatively general regarding the type of patient with heart failure (HF) who should be considered for catheter ablation (CA) of atrial fibrillation (AF). The aim of the present study was to identify clinical predictors and sex differences for treatment with CA in the AF-HF population. Methods: A population-based AF-HF cohort was created using the Quebec administrative data (2000-2017). Patients were followed from the date of diagnosis of both diseases to the date of CA or death. Predictors for CA, represented by time-varying covariates, were assessed in a multivariable Cox model that accounted for the competing risk of death. Results: Among 101,931 patients with AF-HF with medication information (median age, 80.7 years; interquartile range [IQR], 73.9-86.3; 51.4% were female, median CHA2DS2-VASc, 4; IQR, 3-4), only 432 (0.4%) underwent CA after a median of 0.8 years (IQR, 0.1-2.7). Independent of multiple comorbidities and advanced age, which were associated with a lower likelihood of CA, women were approximately half as likely to undergo a CA (26% were women; adjusted hazard ratio, 0.6; 95% confidence interval, 0.4-0.7). Prior use of direct-acting oral anticoagulants and antiarrhythmics, and the presence of an implantable cardioverter-defibrillator were also predictors for CA treatment (P < 0.05 for all). Conclusion: In a real-world population, CA was infrequently used to treat AF among patients with HF, and the likelihood of CA was further reduced in women. Because patients with CA had few comorbidities, future studies need to be conducted to determine whether CA can be beneficial in subjects whose clinical characteristics are more representative of the AF-HF population. Résumé: Contexte: Les lignes directrices actuelles abordent de façon relativement générale les cas d’insuffisance cardiaque (IC) où les patients devraient être considérés comme des candidats à l’ablation par cathéter (AC) pour le traitement de la fibrillation auriculaire (FA). La présente étude visait à cerner les prédicteurs cliniques et les différences entre les sexes dans le contexte de l’AC au sein de la population atteinte de FA et d’IC. Méthodologie: Une cohorte populationnelle de patients atteints de FA et d’IC a été constituée à partir de données administratives du Québec (2000-2017). Le suivi des patients allait de la date du diagnostic des deux affections à la date de l’AC ou du décès. Les prédicteurs d’AC, représentés par des covariables temporalisées, ont été évalués dans un modèle de Cox multivarié tenant compte du risque concurrent de décès. Résultats: Sur 101 931 patients atteints de FA et d’IC dont la médication était documentée (âge médian : 80,7 ans; intervalle interquartile [IIQ] : 73,9-86,3; proportion de patients de sexe féminin : 51,4 %; score CHA2DS2-VASc médian : 4; IIQ : 3-4), seulement 432 (0,4 %) ont subi une AC au bout d’un laps de temps médian de 0,8 an (IIQ : 0,1-2,7). Indépendamment des maladies concomitantes multiples et de l’âge avancé, associés à une moindre probabilité d’AC, les femmes étaient environ deux fois moins susceptibles de subir une AC (proportion de patients de sexe féminin : 26 %; rapport des risques instantanés corrigé : 0,6; intervalle de confiance à 95 % : de 0,4 à 0,7). Les antécédents de traitement par des anticoagulants oraux à action directe et des antiarythmiques, ainsi que la présence d’un défibrillateur cardioverteur implantable étaient également des prédicteurs d’AC (p < 0,05 dans tous les cas). Conclusion: Au sein d’une population en contexte réel, l’AC a été rarement pratiquée pour traiter la FA chez des patients atteints d’IC. En outre, la probabilité d’une AC était moindre chez les femmes. Étant donné que les patients ayant subi une AC présentaient peu de maladies concomitantes, d’autres études devront être menées pour déterminer si l’AC peut être salutaire chez les personnes présentant des caractéristiques cliniques plus représentatives de la population atteinte de FA et d’IC.

Background Atrial fibrillation (AF) and heart failure (HF) are common co-existing conditions. Randomized trial data suggests a reduction in all-cause mortality with catheter ablation (CA) in selected patients, however, whether these results are replicable in a real-world population and persist in the long-term remains to be shown. Purpose To evaluate the long-term effectiveness of CA in AF-HF patients in reducing the incidence of: a) all-cause mortality b) HF hospitalizations, and c) major morbidities (stroke/transient ischemic attack (TIA) and major bleeding). Methods A population-based administrative cohort was created of AF-HF patients with government prescription coverage in Quebec, Canada (1999–2015). Patients who underwent CA (cases) were matched 1:2 to controls using risk-set sampling. Cases were matched on time in the cohort and frequency of hospitalizations. Measured time-invariant confounders were controlled for using inverse probability of treatment weighting (IPTW) and included age, sex, clinical characteristics, presence of cardiac implantable electronic devices, and medication use. Multivariable Cox models adjusted the association of CA with the outcomes for the time varying confounders of the presence of an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT), anticoagulation use (warfarin or direct oral anticoagulation), and any antiarrhythmic (AAD) use during follow-up. For non-fatal outcomes, the competing risk of death was accounted for using the Lunn-McNeil approach. Results Of the 87,676 AF-HF patients, 298 underwent CA and were matched to 591 controls. After IPTW, the distribution of covariates was balanced between cases and controls [age 65.6±11.0 vs 61.6±11.6; women 24% vs 20%; CHA2DS2-Vasc score 3.2±2.3 vs 2.9±2.1; CA vs non-CA, respectively; standardized mean differences Conclusion In a matched population-based AF-HF cohort, CA was associated with a reduced risk of all-cause mortality compared to patients who did not undergo CA. Although no difference in the risk of HF hospitalizations, stroke/TIA, and major bleeding was detected between CA and non-CA patients, larger studies are warranted. Acknowledgement/Funding Canadian Institute of Health Research; Fonds de recherché du Quebec-Santé, Clinical Research Scholar Award (V. Essebag) and Doctoral Award (M. Samuel)

Introduction Catheter ablation (CA) has been increasingly used to treat atrial fibrillation (AF) in patients with heart failure (HF), however, its safety at the population-level has not yet been evaluated. To assess the safety of CA in AF-HF patients, the frequency and potential risk factors for adverse events (AEs) within 30 days post-CA were determined. Methods A population-based cohort of AF-HF patients who underwent CA in Quebec, Canada (2000-2017) was constructed using administrative databases. Major AEs included all-cause mortality, cerebrovascular accident (CVA), pericardial effusion requiring drainage (PERD), vascular AEs, hemorrhage/hematoma, and pulmonary embolism. Univariate logistic regression models were employed to assess potential risk factors for major AEs. Results Of 700 AF-HF patients who underwent CA (median age 64.5 years [interquartile range, IQR, 56.2-71.0], 22.0% female, and median CHA2 DS2 -Vasc 3 [IQR, 2-4]), 14 (2.0%) patients developed 16 major AEs within 30 days of CA. Hemorrhage/hematoma was the most frequent major AE (four patients; 0.6%) followed by all-cause mortality, CVA/TIA, PERD, and vascular AEs (three patients each; 0.4%). Coronary artery disease (odds ratio [OR], 3.9 [95% confidence interval, CI, 1.2-12.3]) and age ≥65 years (OR, 3.1 [95% CI, 1.1-9.8]) were identified predictors for the composite outcome of major AEs. More than half of the patients (57.2%) underwent a second CA within a median of 0.8 (IQR, 0.2-2.2) years from the date of first CA. Conclusion CA performed in the AF-HF population portends a relatively low incidence of major AEs. A larger study is required to determine whether certain patient factors are independently associated with a higher risk of post-CA AEs.

Adults with congenital heart disease are increasingly being exposed to low-dose ionizing radiation (LDIR) from cardiac procedures. In a recent study, Cohen et al. (Circulation. 2018;137(13):1334–1345) reported an association between increased LDIR exposure and cancer incidence but did not explore temporal relationships. Yet, the impact of past exposures probably accumulates over years, and its strength may depend on the amount of time elapsed since exposure. Furthermore, LDIR procedures performed shortly before a cancer diagnosis may have been ordered because of early symptoms of cancer, raising concerns about reversal causality bias. To address these challenges, we combined flexible modeling of cumulative exposures with competing-risks methodology to estimate separate associations of time-varying LDIR exposure with cancer incidence and all-cause mortality. Among 24,833 patients from the Quebec Congenital Heart Disease Database, 602 had incident cancer and 500 died during a follow-up period of up to 15 years (1995–2010). Initial results suggested a strong association of cancer incidence with very recent LDIR exposures, likely reflecting reverse causality bias. When exposure was lagged by 2 years, an increased cumulative LDIR dose from the previous 2–6 years was associated with increased cancer incidence, with a stronger association for women. These results illustrate the importance of accurate modeling of temporal relationships between time-varying exposures and health outcomes.

Background Clinical practice guideline ( CPG ) developers have yet to endorse a consistent and systematic approach for considering sex‐specific cardiovascular information in CPG s. This article describes an initiative led by the Canadian Cardiovascular Society to determine the feasibility and outcomes of a structured process for considering sex in a CPG for the management of ST‐segment–elevation myocardial infarction. Methods and Results A sex and gender champion was appointed to the guideline development committee. The feasibility of tailoring the CPG to sex was ascertained by recording (1) the male–female distribution of the study population, (2) the adequacy of sex‐specific representation in each study using the participation/prevalence ratio, and (3) whether data were disaggregated by sex. The outcome was to determine whether recommendations for CPG s based on an assessment of the evidence should differ by sex. In total, 175 studies were included. The mean percentage of female participants reported in the studies was 24.5% ( SD : 6.6%; minimum: 0%; maximum: 51%). The mean participation/prevalence ratio was 0.62 ( SD : 0.16; minimum: 0.00; maximum: 1.19). Eighteen (10.2%) studies disaggregated the data by sex. Based on the participation/prevalence ratio and the sex‐specific analyses presented, only 1 study provided adequate evidence to confidently inform the applicability of the CPG recommendations to male and female patients. Conclusions Implementing a systematic process for critically appraising sex‐specific evidence for CPG s was straightforward and feasible. Inadequate enrollment and reporting by sex hindered comprehensive sex‐specific assessment of the quality of evidence and strength of recommendations for a CPG on the management of ST‐segment–elevation myocardial infarction.

Background: Post-menopausal women are more likely to have uncontrolled hypertension and are at higher risk of cardiovascular disease compared with age-matched men. Blood pressure variability (BPV) has recently emerged as a predictor of adverse cardiovascular outcomes. It is unknown if there is a relationship between BPV and menopause and whether BPV can predict vascular health in perimenopausal women. Methods: BRAVE (Blood pRessure And Vascular hEalth around menopause) is an observational study recruiting perimenopausal healthy women, aimed at studying the relationship between BPV, the menopause transition and vascular health. A 24-hour blood pressure (BP) measurement [including 24-hour coefficient of variation, night dipping and maximum BP] was used to define the BPV. Menopausal status and cardiovascular risk factors were collected through questionnaires. Arterial stiffness, as a marker of vascular health status, was measured using pulse wave velocity. Multivariable models were performed to identify factors associated with BPV as well as those associated with arterial stiffness in perimenopausal women. Results: Fifty healthy women (mean age 52.9 ± 4.0, 62% post-menopausal) were recruited. There was a low prevalence of cardiovascular risk factors, except physical inactivity (60%). In around 40% of patients, we observed an abnormal pattern of BPV. However, all measures of BPV were similar between peri and post menopausal women. In the multivariable analysis, BMI was the only factor associated independently with maximum overnight BP (ß=1.95, p Conclusion: An abnormal pattern of BPV is common in perimenopausal women with normal office BP measurement. Maximum overnight BP provides useful information on vascular health beyond mean blood pressure in this population. BPV measurements in normotensive perimenopausal women may therefore have additional clinical value in stratifying their cardiovascular risk.

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated. Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD. Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence. Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99). Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner.

Non-communicable diseases (NCDs) are important contributors to maternal morbidity and mortality worldwide. Yet, data on their prevalence and related outcomes in low-income countries are currently lacking. Additionally, screening and treatment protocols adapted for resource-limited settings are urgently required. This collaborative research initiative on the screening and management of hypertensive disorders of pregnancy and gestational diabetes was conducted in Saint-Nicolas Hospital in Saint-Marc, Haiti. The report discusses methods used to overcome several local challenges to implementation of care for NCDs. It also describes how collaborative research initiatives are efficient strategies to innovate and build research capacity for NCD care delivery during pregnancy in low-income countries.

Women with prior hypertensive disorders of pregnancy (HDP) are at twice the risk of cardiovascular disease compared with women with prior normotensive pregnancy, possibly because of sustained vascular dysfunction after delivery. The aim of this systematic review and meta-analysis is to summarize evidence of vascular dysfunction at least 3 months after HDP. Articles in all languages were retrieved from principal databases. Studies included were observational, with HDP as the main exposure and measurements of vascular dysfunction via imaging modalities or serum biomarkers as the main outcome, assessed at least 3 months postpartum. We pooled results of modalities reported in >3 studies using a random effects model. Of 6109 potentially relevant studies, 72 were included that evaluated 10 imaging modalities and 11 serum biomarkers in 8702 women. There was evidence of vascular dysfunction in women post HDP compared with women with prior normal pregnancy when measured by carotid-femoral pulse wave velocity (0.64 m/s [0.17–1.11]), carotid intima–media thickness (0.025 mm [0.004–0.045]), and augmentation index (5.48% [1.58–9.37]), as well as mean levels of soluble fms-like tyrosine kinase (6.12 pg/mL [1.91–10.33]). Between-groups differences in measures of vascular dysfunction were more pronounced when assessments were performed in younger women (

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

Background Following an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. Methods GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond—PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. Results The median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22–8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60–3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23–1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. Conclusion In this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors.

Objective— A genetic risk score (GRS) for coronary artery disease has recently been shown to be independent of family history (FHx) in predicting future cardiovascular events. We sought to determine whether the presence of these risk factors, either individually or together, was associated with a higher burden of angiographic coronary artery disease. Approach and Results— We included 763 patients with premature acute coronary syndrome (median age, 50 [46–53] years; 30.8% women) with at least 1 major epicardial vessel stenosis enrolled in the Gender and Sex Determinants of Cardiovascular Disease From Bench to Beyond in Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, a multicentre prospective cohort study of premature patients with acute coronary syndrome (aged ≤55 years). The prevalence of multivessel disease (ie, ≥2 vessels with >50% stenosis) in individuals with FHx was 49.7% as compared with 37.9% in those without FHx ( P P =0.12 for 2-vessel disease and OR, 2.26; 95% confidence interval, 1.29–3.95; P =0.005 for 3-vessel disease). Individuals with a high GRS were also more likely to have multivessel disease (OR, 1.41; 95% confidence interval, 1.01–1.99; P =0.047) after adjustment for traditional risk factors, including FHx. Individuals with both a FHx and a high GRS as compared with those with neither had the highest ORs for multivessel disease (adjusted OR, 2.14; 95% confidence interval, 1.24–3.69; P =0.0064). Conclusions— In patients with premature acute coronary syndrome, the presence of either a high GRS or FHx is associated with greater severity of coronary artery disease at angiography. Whether preventive strategies targeted to genetically predisposed individuals will reduce the burden of early acute coronary syndrome warrants further study.

Background— The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD. Methods and Results— In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year ( P Conclusions— From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.

SummaryIn elderly patients (≥75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population-based study using administrative databases, in Quebec (1999–2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or ≥ 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3 % being elderly patients. The elderly predominantly used the lower dose (80.1 %) while younger patients mainly used the higher dose (80.0 %). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95 % CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95 % CI: 0.47–0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95 % CI: 1.14–1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding.

Background “Gender” reflects social norms for women and men, whereas “sex” defines biological characteristics. Gender-related characteristics explain some differences in access to care for premature acute coronary syndrome (ACS); whether they are associated with cardiovascular outcomes is unknown. Objectives This study estimated associations between gender and sex with recurrent ACS and major adverse cardiac events (MACE) (e.g., ACS, cardiac mortality, revascularization) over 12 months in patients with ACS. Methods We studied 273 women and 636 men age 18 to 55 years from GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome), a prospective observational cohort study, who were hospitalized for ACS between January 2009 and April 2013. Gender-related characteristics (e.g., social roles) were assessed using a self-administered questionnaire, and a composite measure of gender was derived. Outcomes included recurrent ACS and MACE over 12 months. Results Feminine roles and personality traits were associated with higher rates of recurrent ACS and MACE compared with masculine characteristics. This difference persisted for recurrent ACS, after multivariable adjustment (hazard ratio from score 0 to 100: 4.50; 95% confidence interval: 1.05 to 19.27), and was a nonstatistically significant trend for MACE (hazard ratio: 1.54; 95% confidence interval: 0.90 to 2.66). A possible explanation is increased anxiety, the only condition that was more prevalent in patients with feminine characteristics and that rendered the association between gender and recurrent ACS nonstatistically significant (hazard ratio: 3.56; 95% confidence interval: 0.81 to 15.61). Female sex was not associated with outcomes post-ACS. Conclusions Younger adults with ACS with feminine gender are at an increased risk of recurrent ACS over 12 months, independent of female sex.

Objective The American Heart Association has endorsed depression as a cardiac risk factor and recommends screening as part of routine practice. This has been met with controversy due to inconsistencies in the data linking depression treatment to better cardiovascular outcomes. Our objective was to prospectively assess the association between depression treatment (defined as being prescribed antidepressant medication) and major adverse cardiovascular events (MACE) in patients referred for exercise stress tests. Method Two thousand three hundred eighty-five consecutive patients presenting for myocardial perfusion exercise stress tests underwent a sociodemographic, medical, and psychiatric interview (Primary Care Evaluation of Mental Disorders [PRIME-MD]) and completed the Beck Depression Inventory (BDI). History of cardiovascular disease (CVD) and antidepressant use was self-reported and verified via chart review. Participants followed over an 8.8-year follow up, and information regarding MACE incidence (including cardiac mortality, nonfatal myocardial infarction, revascularization procedures, cerebrovascular events) was obtained from provincial administrative databases. Results 8% (n = 190) of the sample were taking antidepressants at baseline, 41% (n = 916) had a history of CVD, and 38.7% (n = 921) had depression according to the PRIME-MD or BDI. Antidepressant treatment was associated with a 30% reduced risk of MACE (Hazard ratio [HR] = 0.697; 95% confidence interval [CI] = [0.504, 0.964]; p = .029). A 46% reduction in risk was associated with antidepressant treatment among those without CVD (HR = 0.542; 95% CI [0.299, 0.981]; p = .043). In depressed patients, a 33% reduction in risk of MACE associated with antidepressant use was seen (adjusted HR = 0.674; 95% CI [0.440, 1.033]; p = .07). Conclusions Antidepressants may be cardio-protective among patients presenting for stress testing independent of risk factors including CVD and depression. Results support treating depression with antidepressants in this population to reduce risk of MACE. (PsycINFO Database Record (c) 2018 APA, all rights reserved).