Predictors of Health-Related Quality of Life Among Women Participating in an Appointment-Based Cardiac Rehabilitation Program.

BACKGROUND: An alternative patient-centered appointment-based cardiac rehabilitation (CR) program has led to significant improvements in health outcomes for patients with cardiovascular disease. However, less is known about the effects of this approach on health-related quality of life (HRQoL), particularly for women. OBJECTIVE: We examined the effects of a patient-centered appointment-based CR program on HRQoL by sex and examined predictors of HRQoL improvements specifically for women. METHODS: Data were used from an urban single-center CR program at Yale New Haven Health (2012-2017). We collected information on patient demographics, socioeconomic status, and clinical characteristics. The Outcome Short-Form General Health Survey (SF-36) was used to measure HRQoL. We evaluated sex differences in SF-36 scores using t tests and used a multivariate linear regression model to examine predictors of improvements in HRQoL (total SF-36 score) for women. RESULTS: A total of 1530 patients with cardiovascular disease (23.7% women, 4.8% Black; mean age, 64 ± 10.8 years) were enrolled in the CR program. Women were more likely to be older, Black, and separated, divorced, or widowed. Although women had lower total SF-36 scores on CR entry, there was no statistically significant difference in CR adherence or total SF-36 score improvements between sexes. Women who were employed and those with chronic obstructive pulmonary disease were more likely to have improvements in total SF-36 scores. CONCLUSION: Both men and women participating in an appointment-based CR program achieved significant improvements in HRQoL. This approach could be a viable alternative to conventional CR to optimize secondary outcomes for patients.

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.

Sex-Specific Associations of Obstructive Sleep Apnea Risk With Patient Characteristics and Functional Outcomes After Acute Myocardial Infarction: Evidence From the VIRGO Study.

Background Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. Conclusions Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.

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.

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.

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.

Sex Difference in Outcomes of Acute Myocardial Infarction in Young Patients.

BACKGROUND: Younger women experience worse health status than men after their index episode of acute myocardial infarction (AMI). However, whether women have a higher risk for cardiovascular and noncardiovascular hospitalizations in the year after discharge is unknown. OBJECTIVES: The aim of this study was to determine sex differences in causes and timing of 1-year outcomes after AMI in people aged 18 to 55 years. METHODS: Data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young patients with AMI across 103 U.S. hospitals, were used. Sex differences in all-cause and cause-specific hospitalizations were compared by calculating incidence rates ([IRs] per 1,000 person-years) and IR ratios with 95% CIs. We then performed sequential modeling to evaluate the sex difference by calculating subdistribution HRs (SHRs) accounting for deaths. RESULTS: Among 2,979 patients, at least 1 hospitalization occurred among 905 patients (30.4%) in the year after discharge. The leading causes of hospitalization were coronary related (IR: 171.8 [95% CI: 153.6-192.2] among women vs 117.8 [95% CI: 97.3-142.6] among men), followed by noncardiac hospitalization (IR: 145.8 [95% CI: 129.2-164.5] among women vs 69.6 [95% CI: 54.5-88.9] among men). Furthermore, a sex difference was present for coronary-related hospitalizations (SHR: 1.33; 95% CI: 1.04-1.70; P = 0.02) and noncardiac hospitalizations (SHR: 1.51; 95% CI: 1.13-2.07; P = 0.01). CONCLUSIONS: Young women with AMI experience more adverse outcomes than men in the year after discharge. Coronary-related hospitalizations were most common, but noncardiac hospitalizations showed the most significant sex disparity.

Sex Differences in Symptom Complexity and Door-to-Balloon Time in Patients With ST-Elevation Myocardial Infarction.

Greater symptom complexity in women than in men could slow acute ST-elevation myocardial infarction (STEMI) recognition and delay door-to-balloon (D2B) times. We sought to determine the sex differences in symptom complexity and their relation to D2B times in 1,677 young and older patients with STEMI using data from the VIRGO and SILVER-AMI studies. Symptom complexity was defined by the number of symptom patterns or phenotypes and average number of symptoms. The numbers of symptom phenotypes were compared in women and men using the Monte Carlo permutation testing. Groups were also compared using the generalized linear regression and logistic regression. The number of symptom phenotypes (244 vs 171, p = 0.02), mean number of symptoms (4.7 vs 4.2, p <0.001), and mean D2B time (114.6 vs 97.8 minutes, p = 0.004) were greater in young women than in young men but were not significantly different in older women compared with older men. The regression analysis did not show a relation between symptom complexity and D2B time overall; although, chest pain was a significant predictor of D2B times, and young women were more likely to report symptoms other than chest pain. Among patients with STEMI, 36% did not receive percutaneous coronary intervention (PCI), which was associated with presentation delay >6 hours. In patients with STEMI with either D2B time ≥90 minutes or no PCI, women had significantly more symptom phenotypes overall and in VIRGO but not in SILVER-AMI. In conclusion, the markers of symptom complexity were not associated with D2B time overall, but more symptom phenotypes in young women were associated with prolonged D2B time or no PCI. In addition, greater frequency of nonchest pain symptoms in young women may have also slowed the recognition of STEMI and D2B times in young women. Further research on symptoms clusters is needed to improve the recognition of STEMIs to improve the D2B times in young women.

Association of marital/partner status and patient-reported outcomes following myocardial infarction: a systematic review and meta-analysis.

Aims: Little is known about the relationship between marital/partner status and patient-reported outcome measures (PROMs) following myocardial infarction (MI). We conducted a systematic review/meta-analysis and explored potential sex differences. Methods and results: We searched five databases (Medline, Web of Science, Scopus, EMBASE, and PsycINFO) from inception to 27 July 2022. Peer-reviewed studies of MI patients that evaluated marital/partner status as an independent variable and reported its associations with defined PROMs were eligible for inclusion. Results for eligible studies were classified into four pre-specified outcome domains [health-related quality of life (HRQoL), functional status, symptoms, and personal recovery (i.e. self-efficacy, adherence, and purpose/hope)]. Study quality was appraised using Newcastle-Ottawa Scale, and data were synthesized by outcome domains. We conducted subgroup analysis by sex. We included 34 studies (n = 16 712), of which 11 were included in meta-analyses. Being married/partnered was significantly associated with higher HRQoL {six studies [n = 2734]; pooled standardized mean difference, 0.37 [95% confidence interval (CI), 0.12-0.63], I 2 = 51%} but not depression [three studies (n = 2005); pooled odds ratio, 0.72 (95% CI, 0.32-1.64); I 2 = 65%] or self-efficacy [two studies (n = 356); pooled ß, 0.03 (95% CI, -0.09 to 0.14); I 2 = 0%]. The associations of marital/partner status with functional status, personal recovery outcomes, and symptoms of anxiety and fatigue were mixed. Sex differences were not evident due to mixed results from the available studies. Conclusions: Married/partnered MI patients had higher HRQoL than unpartnered patients, but the associations with functional, symptom, and personal recovery outcomes and sex differences were less clear. Our findings inform better methodological approaches and standardized reporting to facilitate future research on these relationships.

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 Differences in Clopidogrel Effects Among Young Patients With Acute Coronary Syndrome: A Role for Genetics?

Background: Poorer health outcomes experienced by young women with acute coronary syndrome may be related to sex differences in the safety and efficacy of antiplatelet agents, such as clopidogrel. Polymorphisms in drug metabolism enzyme (cytochrome P450 [CYP] family) genes are independent factors for the variability in response to clopidogrel. However, a sex-specific impact of genetics to explain worse clinical outcomes in women has not been explored extensively. Therefore, our objective was to determine whether an interaction of sex with CYP variants occurs among users of clopidogrel, and if so, its impact on 1-year adverse clinical outcomes. Methods: We used data from a combined cohort of 2272 patients (median age 49 years; 56% female) hospitalized for acute coronary syndrome. We examined interactions between sex and CYP variants among clopidogrel users at admission and discharge to assess associations with 1-year readmission due to cardiac events. Results: The case-only analysis of 177 participants on clopidogrel at the time of presentation showed that the risk of an atherothrombotic event was greater in female carriers of the CYP2C9∗3 loss-of-function allele (odds ratio = 3.77, 95% confidence interval = 1.54-9.24). The results of the multivariable logistic regression model for users of clopidogrel at discharge (n = 1733) indicated that women had significantly higher risk of atherothrombotic readmissions at 1 year (odds ratio = 1.55, 95% confidence interval = 1.16-2.07), compared to the risk for men, but the loss-of-function alleles, either individually or through a genetic risk score, were not associated with 1-year readmissions. Conclusion: This study highlights the need for an improved understanding of the role of sex-by-gene interactions in causing sex differences in drug metabolism.

Contexte: Les piètres résultats cliniques observés chez les jeunes femmes atteintes d'un syndrome coronarien aigu pourraient être liés à des différences entre les sexes en ce qui concerne l'innocuité et l'efficacité des antiplaquettaires, comme le clopidogrel. Le polymorphisme génétique des enzymes intervenant dans le métabolisme des médicaments (famille des cytochromes P450 [CYP]) est un facteur indépendant de la variabilité de la réponse au clopidogrel. Cependant, jamais la possibilité d'un effet génétique propre au sexe qui expliquerait les résultats cliniques défavorables chez les femmes n'a été examinée en profondeur. Notre objectif était donc de déterminer s'il se produit une interaction entre le sexe et les variants de CYP chez les personnes prenant du clopidogrel et, si tel est le cas, quels sont ses effets sur les résultats cliniques indésirables après un an. Méthodologie: Nous avons utilisé les données d'une cohorte combinée de 2 272 patients (âge médian : 49 ans; 56 % de femmes) hospitalisés en raison d'un syndrome coronarien aigu. Nous avons examiné les interactions entre le sexe et les variants du CYP chez les utilisateurs de clopidogrel au moment de leur admission à l'hôpital et de leur congé pour évaluer les liens entre ces variables et les réhospitalisations après un an en raison d'événements cardiaques. Résultats: L'analyse de cas de 177 participants prenant du clopidogrel au moment de leur admission à l'hôpital a montré que le risque d'événement athérothrombotique était plus élevé chez les femmes porteuses de l'allèle non fonctionnel CYP2C9∗3 (rapport de cotes = 3,77; intervalle de confiance [IC] à 95 % = 1,54 à 9,24). Les résultats obtenus avec le modèle de régression logistique multivariée pour les utilisateurs de clopidogrel au moment du congé (n = 1 733) indiquent que les femmes présentaient un risque significativement plus élevé de réhospitalisation en raison d'un événement athérothrombotique après un an (rapport de cotes = 1,55; [IC] à 95 % = 1,16 à 2,07), comparativement aux hommes. Toutefois, les allèles non fonctionnels, considérés individuellement ou sur la base d'un score de risque génétique, n'étaient pas liés à la réhospitalisation après un an. Conclusion: Cette étude fait ressortir la nécessité de mieux comprendre le rôle de l'interaction sexe-gène dans les différences entre les sexes relativement au métabolisme des médicaments.

The association of marital/partner status with patient-reported health outcomes following acute myocardial infarction or stroke: Protocol for a systematic review and meta-analysis.

INTRODUCTION: Marital/Partner support is associated with lower mortality and morbidity following acute myocardial infarction (AMI) and stroke. Despite an increasing focus on the effect of patient-centered factors on health outcomes, little is known about the impact of marital/partner status on patient-reported outcome measures (PROMs). OBJECTIVE: To synthesize evidence of the association between marital/partner status and PROMs after AMI and stroke and to determine whether associations differ by sex. METHODS AND ANALYSIS: We will search MEDLINE (via Ovid), Web of Science Core Collection (as licensed by Yale University), Scopus, EMBASE (via Ovid), and PsycINFO (via Ovid) from inception to July 15, 2022. Two authors will independently screen titles, abstracts, and then full texts as appropriate, extract data, and assess risk of bias. Conflicts will be resolved by discussion with a third reviewer. The primary outcomes will be the associations between marital/partner status and PROMs. An outcome framework was designed to classify PROMs into four domains (health-related quality of life, functional status, symptoms, and personal recovery). Meta-analysis will be conducted if appropriate. Subgroup analysis by sex and meta-regression with a covariate for the proportion of male participants will be performed to explore differences by sex. ETHICS AND DISSEMINATION: This research is exempt from ethics approval because the study will be conducted using published data. We will disseminate the results of the analysis in a related peer-reviewed journal. TRIAL REGISTRATION: PROSPERO registration number: CRD42022295975.

PreScription DigitaL ThErapEutic for Patients with Insomnia (SLEEP-I): a protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04909229.

Interventions Targeted to Address Social Determinants of Health in Ischemic Heart Disease: A Sex- and Gender-Oriented Scoping Review.

The burden of ischemic heart disease (IHD) is a major health problem worldwide. The detrimental effect of gendered (ie, unevenly distributed between female and male) socioeconomic determinants of health (SDOH) on outcomes has been demonstrated, more so in female individuals. Therefore, addressing SDOH is a priority for the care implementation of patients with IHD. We conducted a scoping review to identify the types of SDOH-tailored interventions tested in randomised controlled trials (RCTs) among IHD patients, and whether the reporting of findings was sex-unbiased. We identified 8 SDOH domains: education, physical environment, health care system, economic stability, social support, sexual orientation, culture/language, and systemic racism. A total of 28 RCTs (2 ongoing) were evaluated. Since the 1990s, 26 RCTs have been conducted, mainly in the Middle East and Asia, and addressed only education, physical environment, health care system, and social support. The 77% of studies focused on patient-education interventions, and around 80% on SDOH-based interventions achieved positive effects on a variety of primary outcome(s). Among the limitations of the conducted RCTs, the most relevant were an overall low participation of female and racial/ethnical minority participants, a lack of sex-stratified analyses, and a missing opportunity of tailoring some SDOH interventions relevant for health. The SDOH-tailored interventions tested so far in RCTs, enrolling predominantly male patients and mainly targeting education and health literacy, were effective in improving outcomes among patients with IHD. Future studies should focus on a wider range of SDOH with an adequate representation of female and minority patients who would most benefit from such interventions.

Hemodynamic differences between women and men with elevated blood pressure in China: A non-invasive assessment of 45,082 adults using impedance cardiography.

BACKGROUND: Whether there are sex differences in hemodynamic profiles among people with elevated blood pressure is not well understood and could guide personalization of treatment. METHODS AND RESULTS: We described the clinical and hemodynamic characteristics of adults with elevated blood pressure in China using impedance cardiography. We included 45,082 individuals with elevated blood pressure (defined as systolic blood pressure of ≥130 mmHg or a diastolic blood pressure of ≥80 mmHg), of which 35.2% were women. Overall, women had a higher mean systolic blood pressure than men (139.0 [±15.7] mmHg vs 136.8 [±13.8] mmHg, P<0.001), but a lower mean diastolic blood pressure (82.6 [±9.0] mmHg vs 85.6 [±8.9] mmHg, P<0.001). After adjusting for age, region, and body mass index, women <50 years old had lower systemic vascular resistance index (beta-coefficient [ß] -31.7; 95% CI: -51.2, -12.2) and higher cardiac index (ß 0.07; 95% CI: 0.04, 0.09) than men of their same age group, whereas among those ≥50 years old women had higher systemic vascular resistance index (ß 120.4; 95% CI: 102.4, 138.5) but lower cardiac index (ß -0.15; 95% CI: -0.16, -0.13). Results were consistent with a propensity score matching sensitivity analysis, although the magnitude of the SVRI difference was lower and non-significant. However, there was substantial overlap between women and men in the distribution plots of these variables, with overlapping areas ranging from 78% to 88%. CONCLUSIONS: Our findings indicate that there are sex differences in hypertension phenotype, but that sex alone is insufficient to infer an individual's profile.

Implementation of an Appointment-Based Cardiac Rehabilitation Approach: A Single-Center Experience.

Background There has been a focus on alternative cardiac rehabilitation (CR) delivery models aimed at improving CR adherence and completion. We examined pre- and post-CR health outcomes, reasons for discharge, and predictors of completion using a patient-driven appointment-based CR approach that uses center-scheduled class start times. Methods and Results Data were used from an urban single-center CR program at Yale New Haven Health (2012-2017) that enrolled 2135 patients. We evaluated pre- and post-CR outcomes (12 weeks) using paired t tests and used a multivariable logistic regression model to examine predictors of CR completion (≥36 sessions) for the overall cardiovascular disease population. The mean age of participants was 65±12 years, 27.9% were women, and 5.1% were Black patients, and patients completed a median of 30 of 36 sessions. Patients achieved significant improvements in health outcomes, including across age and sex subgroups. The primary reason for discharge was completion of all 36 sessions of CR (46.4%). The final logistic regression model contained 12 predictors: age, sex, Black race, marital status, employment, number of physician-reported risk factors, dietary fat intake >30%, obesity, lack of exercise, benign prostatic hyperplasia, and self-reported stress and physical activity. Conclusions We demonstrated that patients participating in an appointment-based CR program achieved significant improvements in health outcomes and across sex/age subgroups. In addition, older individuals were more likely to complete CR. An appointment-based approach could be a viable alternative CR method to aid in optimizing the dose-response benefit of CR for patients with cardiovascular disease.

Sex Differences in Characteristics, Treatments, and Outcomes Among Patients Hospitalized for Non-ST-Segment-Elevation Myocardial Infarction in China: 2006 to 2015.

BACKGROUND: Sex differences in clinical characteristics and in-hospital outcomes among patients with non-ST-segment-elevation myocardial infarction have been described in Western countries, but whether these differences exist in China is unknown. METHODS: We used a 2-stage random sampling design to create a nationally representative sample of patients admitted to 151 Chinese hospitals for non-ST-segment-elevation myocardial infarction in 2006, 2011, and 2015 and examined sex differences in clinical profiles, treatments, and in-hospital outcomes over this time. Multivariable logistic regression models adjusting for age or other potentially confounding clinical covariates were used to estimate these sex-specific differences. RESULTS: Among 4611 patients, the proportion of women (39.8%) was unchanged between 2006 and 2015. Women were older with higher rates of hypertension, diabetes, and dyslipidemia. Among patients without contraindications, women were less likely to receive treatments than men, with significant differences for aspirin in 2015 (90.3% versus 93.9%) and for invasive strategy in 2011 (28.7% versus 45.7%) and 2015 (34.0% versus 48.4%). After adjusting for age, such differences in aspirin and invasive strategy in 2015 were not significant, but the difference in invasive strategy in 2011 persisted. The sex gaps in the use of invasive strategy did not narrow. From 2006 to 2015, a significant decrease in in-hospital mortality was observed in men (from 16.9% to 8.7%), but not in women (from 11.8% to 12.0%), with significant interaction between sex and study year (P=0.023). After adjustment, in-hospital mortality in women was significantly lower than men in 2006, but not in 2011 or 2015. CONCLUSIONS: Sex differences in cardiovascular risk factors and invasive strategy after non-ST-segment-elevation myocardial infarction were observed between 2011 and 2015 in China. Although sex gaps in in-hospital mortality were largely explained by age differences, efforts to narrow sex-related disparities in quality of care should remain a focus. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique identifier: NCT01624883.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

Sex-Specific Risk Factors Associated With First Acute Myocardial Infarction in Young Adults.

Importance: An increasing proportion of people in the US hospitalized for acute myocardial infarction (AMI) are younger than 55 years, with the largest increase in young women. Effective prevention requires an understanding of risk factors associated with risk of AMI in young women compared with men. Objectives: To assess the sex-specific associations of demographic, clinical, and psychosocial risk factors with first AMI among adults younger than 55 years, overall, and by AMI subtype. Design, Setting, and Participants: This study used a case-control design with 2264 patients with AMI, aged 18 to 55 years, from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study and 2264 population-based controls matched for age, sex, and race and ethnicity from the National Health and Nutrition Examination Survey from 2008 to 2012. Data were analyzed from April 2020 to November 2021. Exposures: A wide range of demographic, clinical, and psychosocial risk factors. Main Outcomes and Measures: Odds ratios (ORs) and population attributable fractions (PAF) for first AMI associated with demographic, clinical, and psychosocial risk factors. Results: Of the 4528 case patients and matched controls, 3122 (68.9%) were women, and the median (IQR) age was 48 (44-52) years. Seven risk factors (diabetes [OR, 3.59 (95% CI, 2.72-4.74) in women vs 1.76 (1.19-2.60) in men], depression [OR, 3.09 (95% CI, 2.37-4.04) in women vs 1.77 (1.15-2.73) in men], hypertension [OR, 2.87 (95% CI, 2.31-3.57) in women vs 2.19 (1.65-2.90) in men], current smoking [OR, 3.28 (95% CI, 2.65-4.07) in women vs 3.28 (2.65-4.07) in men], family history of premature myocardial infarction [OR, 1.48 (95% CI, 1.17-1.88) in women vs 2.42 (1.71-3.41) in men], low household income [OR, 1.79 (95% CI, 1.28-2.50) in women vs 1.35 (0.82-2.23) in men], hypercholesterolemia [OR, 1.02 (95% CI, 0.81-1.29) in women vs 2.16 (1.49-3.15) in men]) collectively accounted for the majority of the total risk of AMI in women (83.9%) and men (85.1%). There were significant sex differences in risk factor associations: hypertension, depression, diabetes, current smoking, and family history of diabetes had stronger associations with AMI in young women, whereas hypercholesterolemia had a stronger association in young men. Risk factor profiles varied by AMI subtype, and traditional cardiovascular risk factors had higher prevalence and stronger ORs for type 1 AMI compared with other AMI subtypes. Conclusions and Relevance: In this case-control study, 7 risk factors, many potentially modifiable, accounted for 85% of the risk of first AMI in young women and men. Significant differences in risk factor profiles and risk factor associations existed by sex and by AMI subtype. These findings suggest the need for sex-specific strategies in risk factor modification and prevention of AMI in young adults. Further research is needed to improve risk assessment of AMI subtypes.